WorldWideScience

Sample records for alemtuzumab immunosuppressive therapy

  1. Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James; Chang, J Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J; Van Der Weyden, Carrie; Prince, H Miles; Cameron, Paul U; Lewin, Sharon R

    2017-08-24

    To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells. Case report. Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells. Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

  2. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Badoux, Xavier C; Keating, Michael J; Wang, Xuemei; O'Brien, Susan M; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop; Wierda, William G

    2011-08-25

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.

  3. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    DEFF Research Database (Denmark)

    Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

    2012-01-01

    The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

  4. Alemtuzumab (Millennium/ILEX).

    Science.gov (United States)

    Dumont, F J

    2001-01-01

    Alemtuzumab, a lymphocyte-depleting humanized monoclonal antibody, is being developed by Millennium Pharmaceuticals Inc and ILEX Oncology for the potential treatment of chronic lymphocytic leukemia (CLL) [274580]. The utility of the compound for treating bone marrow (BM) stem cell transplantation-associated graft-versus-host disease (GVHD) [372946] and for ex vivo purging of BM to remove malignant T-cells [244056] is also being investigated. Additional potential therapeutic areas for which clinical trials are planned or ongoing include vasculitis, multiple sclerosis [288762] and organ transplantation [338304]. A Biologics License Application (BLA) was filed with the FDA in December 1999 by ILEX and Millennium [351523], [351524], [373873]. The FDA accepted the application for filing in February 2000 [355775] and returned a complete response letter in June 2000 [372172]. Millennium and ILEX submitted a response to the FDA in August 2000 [379766]. Alemtuzumab has received Fast Track designation [304771] and orphan drug status from the FDA [288762], and the drug was reviewed by the FDA's Oncologic Drugs Advisory Committee on 14 December, 2000 [387228]. The committee voted 14 to 1 to recommend accelerated approval of alemtuzumab for patients with CLL who have been treated with alkylating agents and who have failed fludarabine therapy [393778], [393894]. In March 2000, Millennium and ILEX also submitted a Marketing Authorization Application (MAA) for alemtuzumab to the European Agency for the Evaluation of Medicinal Products (EMEA) [363595]. In October 2000, EMEA accepted the MAA for alemtuzumab under the agency's centralized approval procedure [387228]. Alemtuzumab was originally synthesized by Herman Waldmann and colleagues at Cambridge University and licensed to Burroughs Wellcome (BW) via the British Technology Group (BTG) [162622]. BW conducted phase I and II trials for a broad range of indications, but then discontinued development because of disappointing results

  5. Alemtuzumab Injection

    Science.gov (United States)

    ... which too many of a certain type of white blood cell accumulate in the body). Alemtuzumab is ... In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has ...

  6. Rhodococcus equi infection after alemtuzumab therapy for T-cell prolymphocytic leukemia

    NARCIS (Netherlands)

    Meeuse, Jan J.; Sprenger, Herman G.; Van Assen, Sander; Leduc, Dominique; Daenen, Simon M.G.J.; Arends, Jan P.; van der Werf, Tjipke

    2007-01-01

    Rhodococcus equi, mainly known from veterinary medicine as a pathogen in domestic animals, can also cause infections in immunocompromised humans, especially in those with defects in cellular immunity. Alemtuzumab, an anti-CD52 monoclonal antibody, causes lymphocytopenia by eliminating CD52-positive

  7. Norovirus-related chronic diarrhea in a patient treated with alemtuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Ronchetti, Anne-Marie; Henry, Benoit; Ambert-Balay, Katia; Pothier, Pierre; Decroocq, Justine; Leblond, Véronique; Roos-Weil, Damien

    2014-05-06

    Norovirus infection is increasingly recognized as an important cause of persistent gastroenteritis in immunocompromised hosts and can be a potential cause of morbidity in these populations. Here, we report a case of norovirus-related chronic diarrhea occurring in a 62-year-old immunocompromised patient treated with alemtuzumab for chronic lymphocytic leukemia. Despite different therapeutic strategies including tapering of immunosuppressive therapy and immunoglobulin administration, diarrhea unfortunately did not resolve and lasted for a total of more than twelve weeks with prolonged norovirus fecal excretion. Norovirus infection can occur in the setting of alemtuzumab treatment, even as a single agent, and should be included in the differential diagnoses of acute and chronic diarrhea in these immunocompromised patients. Although the administration of oral immunoglobulin has been described as a promising efficient therapy, this was not the case in our patient. Clinical trials are thus clearly warranted to better define risk factors and efficient therapies for norovirus infection in immunocompromised populations.

  8. Alemtuzumab (Campath-1H) in kidney transplantation.

    Science.gov (United States)

    Ciancio, G; Burke, G W

    2008-01-01

    Kidney transplantation has become the treatment of choice for both the quality of life and survival in patients with end-stage renal disease (ESRD). However, the immunosuppressive regimen which allows optimal kidney transplant outcome remains elusive. One of the more promising induction agents, Alemtuzumab, was introduced to kidney transplantation by Calne in the late 1990s with low dose cyclosporine A monotherapy, with the hope of establishing 'prope' or near tolerance. Subsequent pilot studies with Alemtuzumab alone or monotherapy (DSG, Rapa) demonstrated high rates of acute rejection (AR) along with occasional humoral components that lead to abandoning the concept of Alemtuzumab as a 'magic bullet' to achieve tolerance, prope or otherwise. A number of programs (including our own) has since modified maintenance immunosuppression using low dose tacrolimus, and shown acceptable rates of AR, with relatively low incidence of viral infection and lymphoproliferative disorders along with cost benefit. However, there are only three prospective, randomized studies which are small with one year or less follow-up, and most published series utilize historical control groups with relatively short follow-up. As extrapolation from short-term data is far from secure, long-term, prospective, randomized studies with Alemtuzumab will be necessary to determine the optimal immunosuppressive regimen.

  9. Tubulointerstitial nephritis and uveitis syndrome (TINU). Treatment with immunosuppressive therapy.

    Science.gov (United States)

    Rueda-Rueda, T; Sánchez-Vicente, J L; Moruno-Rodríguez, A; Castilla-Martino, M; López-Herrero, F; Contreras-Díaz, M; Molina-Socola, F; Sáez-Ortega, L; Muñoz-Morales, A

    2018-01-01

    Two cases of tubulointerstitial nephritis and uveitis are presented. Immunosuppressive therapy was required to control the uveitis. Contrary to that usually described, uveitis became chronic, which made immunosuppressive therapy necessary. Nephritis was successfully treated with steroids. Tubulointerstitial nephritis and uveitis syndrome is an under-diagnosed disorder and requires clinical suspicion due to there being no specific laboratory study available. Recurrences and relapses of ocular inflammation are common. Immunosuppressive therapy is not often needed. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Nail changes in female pemphigus vulgaris patients on immunosuppressive therapy ?

    OpenAIRE

    El-Komy, M.M.; Abdel Halim, D.M.; Samir, N.; Hegazy, R.A.; Gawdat, H.I.; Shoeb, S.A.

    2015-01-01

    Background: Pemphigus vulgaris (PV) patients receiving immunosuppressive therapy may develop nail alterations resulting from infection, skin disorder, or drug regimen. Objective: This study aims to describe nail changes in PV female patients receiving immunosuppressive therapy and to report the frequency of associated fungal and bacterial growth in the patients’ nails. Methods: Twenty-five female PV patients who had at least one acquired finger or toenail abnormality and had been admini...

  11. Immunosuppressants

    Science.gov (United States)

    ... Brain Death HIV and Kidney Transplantation/Donation Incompatible Blood Types and Paired Exchange Programs Knowing Your Immunosuppressive (anti-rejection) Medications Organ and Tissue Donation The National Kidney ...

  12. Nail changes in female pemphigus vulgaris patients on immunosuppressive therapy.

    Science.gov (United States)

    El-Komy, M M; Abdel Halim, D M; Samir, N; Hegazy, R A; Gawdat, H I; Shoeb, S A

    2015-06-01

    Pemphigus vulgaris (PV) patients receiving immunosuppressive therapy may develop nail alterations resulting from infection, skin disorder, or drug regimen. This study aims to describe nail changes in PV female patients receiving immunosuppressive therapy and to report the frequency of associated fungal and bacterial growth in the patients' nails. Twenty-five female PV patients who had at least one acquired finger or toenail abnormality and had been administered at least one immunosuppressive drug were included in the study. Nail alterations were recorded. Nail scrapings were collected from abnormal nails for fungal and bacterial examination. Positive fungal and bacterial cultures were detected in 20 (80%) of patients' nail samples. Five patients reported nail alterations coinciding with disease onset, whereas 13 reported nail changes after administration of immunosuppressive therapy. Lack of a control group (patients on similar immunosuppressive medications for conditions other than PV) which would have further supported the findings demonstrated in this observational study. Nail abnormalities in severe PV patients are frequently associated with fungal and bacterial growth. Immunosuppressive therapy potentially initiates such changes.

  13. Alemtuzumab for the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Willis MD

    2015-03-01

    Full Text Available Mark D Willis, Neil P Robertson Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK Abstract: Alemtuzumab is an anti-CD52 monoclonal antibody, recently approved for the treatment of active, relapsing multiple sclerosis (MS. Administration of alemtuzumab causes a rapid and dramatic reduction in circulating lymphocytes, with a predictable subsequent pattern of immune reconstitution. Although the precise mode of action remains unclear, treatment results in a marked reduction in annualized relapse rates, slowing of disability progression compared with an active comparator, and may even cause disability reversal. Although conferring clear clinical benefits, alemtuzumab carries a significant long-term risk of autoimmune disease (AID, which has a particular predilection for the thyroid gland, although a wide range of other disorders have also been reported. However, risks of AID can usually be anticipated and treated successfully, provided rigorous monitoring and surveillance protocols are followed by clinicians and patients alike. Despite its immunosuppressive mechanism of action serious infections are rare and malignancies commonly associated with immunodeficiency have not been observed to date. Alemtuzumab’s unique mode of administration, as well as it’s durability of effect, provides an important addition to currently available therapeutic interventions for MS, and in particular is a valuable treatment option in recent onset and highly active relapsing disease. Keywords: multiple sclerosis, alemtuzumab, autoimmune disease

  14. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to a1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  15. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  16. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  17. The evolving role of alemtuzumab (Campath-1H in renal transplantation

    Directory of Open Access Journals (Sweden)

    Phuong-Thu T Pham

    2008-12-01

    Full Text Available Phuong-Thu T Pham1, Gerald S Lipshutz2, Phuong-Truc T Pham3, Joseph Kawahji1, Jennifer S Singer4, Phuong-Chi T Pham51Division of Nephrology, Department of Medicine, Kidney and Pancreas Transplant Program, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California; 2Kidney and Pancreas Transplant Program, Department of Surgery and Urology, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California; 3Department of Science, Penn State University, Worthington-Scranton, Dunmore, Pennsylvania; 4Renal Transplantation and Pediatric Urology, Department of Urology, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California; 5Division of Nephrology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, and Olive-View-UCLA Medical Center, Sylmar, California, USAAbstract: The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has resulted in excellent short-term graft survival. Nonetheless, extended long-term graft outcomes have not been achieved due in part to the nephrotoxic effects of calcineurin inhibitors (CNIs and the adverse effects of steroid on cardiovascular disease risk factors. Induction therapy with lymphocyte depleting antibodies has originally been introduced into renal transplantation to provide intense immunosuppression in the early post-transplant period to prevent allograft rejection. Over the past half decade, induction therapy with both non-lymphocyte depleting (basiliximab and daclizumab and lymphocyte-depleting antibodies (antithymocyte antibodies, OKT3, alemtuzumab has increasingly been utilized in steroid or CNI sparing protocols in the early postoperative period. Alemtuzumab is a humanized monoclonal antibody targeted against CD52 on the surface of circulatory mononuclear cells. The ability of alemtuzumab (Campath-1H to

  18. Malaria in immuno-suppressed individuals on antiretroviral therapy ...

    African Journals Online (AJOL)

    Malaria in immuno-suppressed individuals on antiretroviral therapy (ART) in north-central Nigeria. C.R. Pam, B.T. Abubakar, G.O. Inwang, G.A. Amuga. Abstract. The immune deficiency caused by HIV infection reduces the immune response to malaria parasitaemia and therefore leads to an increased frequency of clinical ...

  19. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

    OpenAIRE

    Seto, Wai-Kay

    2015-01-01

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negati...

  20. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification.

    Science.gov (United States)

    Seto, Wai-Kay

    2015-04-28

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.

  1. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

    Directory of Open Access Journals (Sweden)

    Tobias Ruck

    2015-07-01

    Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

  2. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cohen, Jeffrey A; Coles, Alasdair J

    2016-01-01

    OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CAR...

  3. Adherence to immunosuppressive therapy following liver transplantation: an integrative review

    Directory of Open Access Journals (Sweden)

    Ramon Antônio Oliveira

    Full Text Available ABSTRACT Objective: to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. Method: integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. Results: were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. Conclusion: there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill.

  4. Immunosuppression in lung transplantation.

    Science.gov (United States)

    Scheffert, Jenna L; Raza, Kashif

    2014-08-01

    Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

  5. Understanding the positive benefit:risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical Development Program

    Directory of Open Access Journals (Sweden)

    Havrdova E

    2017-10-01

    Full Text Available Eva Havrdova,1 Jeffrey A Cohen,2 Dana Horakova,1 Ivana Kovarova,1 Eva Meluzinova3 1Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; 2Neurological Institute, Cleveland Clinic, Cleveland, OH, USA; 3Department of Neurology, Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic Abstract: The introduction of high-efficacy therapies for relapsing–remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss. In two of the studies, alemtuzumab-treated patients had a significantly reduced risk of 6-month confirmed disease worsening, compared with subcutaneous interferon beta-1a. Benefits were maintained throughout 5 years, with a majority of patients receiving no alemtuzumab retreatment or other disease-modifying therapy. Trial results support alemtuzumab’s manageable, consistent safety profile in relapsing–remitting multiple sclerosis. Infusion-associated reactions, the most frequent adverse events (AEs, can be minimized by corticosteroid pretreatment, monitoring, and symptomatic management. Other AEs include infections and autoimmune events. Oral anti-herpes prophylaxis should be initiated on the first day of each alemtuzumab treatment course and continued according to local guidelines. Overall cancer risk was lower in the alemtuzumab clinical trials than in a reference population; however, continuing surveillance will determine if alemtuzumab may be associated with

  6. Peri-operative alemtuzumab (Campath-1H) and plasmapheresis for high-PRA positive lymphocyte crossmatch heart transplant: a strategy to shorten left ventricular assist device support.

    Science.gov (United States)

    Lick, Scott D; Vaidya, Smita; Kollar, Andras C; Boor, Paul J; Vertrees, Roger A

    2008-09-01

    Patients on a left ventricular assist device (LVAD) often have a high level of panel-reactive antibodies (PRA). Conventional therapy is to await a heart from a negative prospective-crossmatch donor. We transplanted three high-PRA patients with non-crossmatched hearts, using intra- and post-operative plasmapheresis and long-term T-/B-/plasma-cell therapy with alemtuzumab. Three highly sensitized patients (70%, 94% and 96% T-PRA; 63%, 24% and 73% B-PRA) were transplanted after 29, 187 and 94 days LVAD support. The first patient (Case 1) had an erroneous prospective negative crossmatch (due to an outside laboratory's use of the wrong patient's serum) with immediate allograft dysfunction. The correct serum showed a strongly positive crossmatch; plasmapheresis followed by alemtuzumab (20 mg intravenously) shortly after arrival in the ICU resulted in rapid hemodynamic improvement. Encouraged by this success, the next two patients (Cases 2 and 3) underwent LVAD explant and heart transplant with the next available ABO-identical, non-crossmatched donors, using plasmapheresis on bypass immediately before heart implant and alemtuzumab 20 mg intravenously upon ICU arrival, with uneventful courses. All three patients had positive retrospective T- and B-cell crossmatches. Maintenance immunosuppression consisted of cyclosporine and routine prednisone taper, with plasmapheresis as needed (Patient 1, x10; Patient 2, x5) based on diastolic dysfunction. Mycophenolate mofetil was started as a third agent several months post-transplant. Patients are presently New York Heart Association (NYHA) Class I at 26, 16 and 13 months post-transplant. In this small series with follow-up, immediate antibody removal with plasmapheresis, combined with alemtuzumab, a long-acting antibody to CD52 (expressed on T, B and some plasma cells), appears effective in allowing transplantation in sensitized, positive crossmatch recipients. Expanded use of this strategy could shorten LVAD support in many

  7. Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

    LENUS (Irish Health Repository)

    Gabardi, Steven

    2011-09-01

    To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.

  8. Alemtuzumab: evidence for its potential in relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Brown JWL

    2013-03-01

    Full Text Available J William L Brown, Alasdair J ColesDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKAbstract: Alemtuzumab (previously known as Campath® is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing–remitting multiple sclerosis. One Phase II and two Phase III trials of alemtuzumab versus active comparator (interferon beta-1a have been reported. Two of these rater-blinded randomized studies assessed clinical and radiological outcomes in treatment-naïve patients; one explored patients who had relapsed despite first-line therapy. Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%–74% (P < 0.0001, and in two studies it reduced the risk of sustained disability accumulation by 42%–71% (P < 0.01. In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1, there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group. After alemtuzumab, the Expanded Disability Status Scale score improved by 0.14–1.2 points, culminating in a net advantage with alemtuzumab of 0.41–0.77 points over interferon in the CAMMS223 and CARE-MS2 trials (both P < 0.001. Radiological markers of new lesion formation and brain atrophy following alemtuzumab were significantly improved when compared to interferon in all studies. Adverse events were more common following alemtuzumab than interferon beta-1a (7.2–8.66 versus 4.9–5.7 events per person-year. While infusion reactions are the most common, autoimmunity is the most concerning; within Phase III studies, thyroid disorders (17%–18% versus 5%–6% and immune thrombocytopenic purpura (1% versus 0% were reported in patients taking alemtuzumab and interferon beta-1a

  9. Immunizations in Children with Inflammatory Bowel Disease Treated with Immunosuppressive Therapy

    OpenAIRE

    Lu, Ying; Bousvaros, Athos

    2014-01-01

    The vast majority of patients with inflammatory bowel disease (IBD) will receive immunosuppressive therapy at some point for their disease, whether for the short term (such as a course of corticosteroids) or long term (such as maintenance therapy with immunomodulators or biologics). The systemic immunosuppression places patients at increased risk for infections. Therefore, it is important that patients are up-to-date with immunizations to minimize vaccine-preventable infections. However, the ...

  10. A Danish nationwide questionnaire study of hepatitis B virus screening before immunosuppressive therapy

    DEFF Research Database (Denmark)

    Bunyoz, Kristine Ifigenia; Krarup, Henrik; Weis, Nina

    2017-01-01

    INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation...... of immunosuppressive therapy and to explore HBV treatment strategies. METHODS: All Danish units of haematology, oncology, dermatology, rheumatology and gastroenterology using immunosuppressive agents were invited to fill out a questionnaire for The Danish Database for Hepatitis B and C. RESULTS: A total of 28 (53...

  11. A Danish nationwide questionnaire study of hepatitis B virus screening before immunosuppressive therapy

    DEFF Research Database (Denmark)

    Bunyoz, Kristine Ifigenia; Krarup, Henrik; Weis, Nina

    2017-01-01

    INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation...... of immunosuppressive therapy and to explore HBV treatment strategies. METHODS: All Danish units of haematology, oncology, dermatology, rheumatology and gastroenterology using immunosuppressive agents were invited to fill out a questionnaire for The Danish Database for Hepatitis B and C. RESULTS: A total of 28 (53......%) of the 53 included units answered the questionnaire, of which 25 (89.3%) had a guideline regarding screening for HBV serological markers prior to immunosuppressive therapy, but only ten (37%) had a guideline that is in line with the joint guidelines from the national Danish Societies of Infectious Diseases...

  12. Emergence of cutaneous neosporosis in a dog receiving immunosuppressive therapy: molecular identification and management.

    Science.gov (United States)

    Legnani, Sara; Pantchev, Nikola; Forlani, Annalisa; Zini, Eric; Schares, Gereon; Balzer, Jörg; Roccabianca, Paola; Ferri, Filippo; Zanna, Giordana

    2016-02-01

    Neosporosis is a multisystemic disease caused by the intracellular protozoan Neospora caninum. In dogs the disease primarily affects the central nervous system. Canine cutaneous neosporosis is a rare condition often associated with old age or concurrent immunosuppressive treatments for different underlying conditions. A 10-year-old female spayed golden retriever dog affected by primary immune-mediated myelofibrosis and treated with immunosuppressive therapies for 6 weeks that developed severe cutaneous lesions. Definitive diagnosis was based on several investigation techniques including serology (immunoblotting), immunohistochemistry (IHC), species-specific conventional and real-time PCR, and DNA sequencing. Remission of cutaneous neosporosis was obtained with the administration of clindamycin while the concurrent immunosuppressive therapy was maintained to manage the underlying primary condition. To the best of the authors' knowledge this is the first report of species-specific PCR and DNA sequencing used as diagnostic methods for canine cutaneous neosporosis emerging in a dog receiving immunosuppressive therapy. © 2015 ESVD and ACVD.

  13. Adherence to immunosuppressive therapy following liver transplantation: an integrative review.

    Science.gov (United States)

    Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

    2016-08-29

    to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. investigar as evidências disponíveis na literatura sobre a não adesão à terapêutica imunossupressora entre pacientes submetidos ao transplante de fígado. revisão integrativa da literatura, que incluiu investigações cuja amostra era composta por pacientes com idade igual ou superior a 18 anos, submetidos a transplante de fígado. Excluíram-se as que continham pacientes submetidos a transplantes de múltiplos órgãos. Para a seleção dos artigos foram consultadas as bases Medline/Pubmed, CINAHL, LILACS, Scopus e Embase. O período de busca determinado correspondeu à data inicial de indexação das

  14. Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

    Science.gov (United States)

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  15. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  16. Intestinal strongyloidiasis in a psoriatic patient following immunosuppressive therapy: Seeing the unforeseen

    Directory of Open Access Journals (Sweden)

    Poongodi Lakshmi Santhana Kumaraswamy

    2016-01-01

    Full Text Available Strongyloides stercoralis , an intestinal nematode, has a complicated life cycle. Mostly asymptomatic, if symptomatic it has nonspecific, transient clinical manifestations. The two aggressive forms of the disease are: Hyperinfection syndrome (HS or disseminated syndrome (DS. Several risk factors have been associated with strongyloidiasis including immunosuppressive therapy, human immunodeficiency virus (HIV infection, diabetes, alcoholism, tuberculosis, impaired bowel motility, surgically created intestinal blind loops, chronic obstructive pulmonary disease, and chronic renal failure. We describe a case of intestinal strongyloidiasis in a psoriatic patient treated with immunosuppressive therapy.

  17. [Immunosuppressive therapy and fertility preservation: Indications and methods].

    Science.gov (United States)

    Choux, C; Cavalieri, M; Barberet, J; Samson, M; Bonnotte, B; Fauque, P; Sagot, P

    2018-02-27

    Fertility preservation is routinely performed in cancerology but less systematically used in the field of immune diseases, even though the use of gonadotoxic treatments in young patients may be required and even though the disease itself can alter fertility. This review aimed to clarify the indications and methods of fertility preservation in this context. Cyclophosphamide is the only immunosuppressive drug requiring fertility preservation in women. In men, fertility preservation should be proposed before treatment with cyclophosphamide, methotrexate, mycophenolate mofetil or mTOR inhibitors. Other factors inherent to the disease or the patient may alter fertility. Thus, screening for infertility and fertility preservation have to be implemented as much as possible to increase the chances of successful procreation in patients with immune disease. For women, the choice between the different preservation methods depends on the patient's age, disease activity, the time available before the start of treatment, the possibility of future pregnancy and the woman's and even couple's wishes. Before puberty, the only accepted method is cryopreservation of ovarian tissue. After puberty, the first-line method is the cryopreservation of mature oocytes. If the treatment has to be started in an emergency, if ovarian hyperstimulation/oocyte retrieval is contraindicated or if the patient refuses this option, cryopreservation of ovarian tissue or GnRH agonists could be proposed. For men, the accepted method is sperm cryopreservation. For prepubertal boys, the cryopreservation of spermatogonia after testicular biopsy is still experimental. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. [My patient will receive immunosuppressive therapy : which vaccination for each situation ?

    Science.gov (United States)

    Moschouri, Eleni; Bart, Pierre-Alexandre

    2016-11-23

    The number of patients whose immune responses are impaired is increasing over the years due to larger use of immunosuppressive therapies aiming at treating malignant, autoimmune or inflammatory diseases. These patients are at high risk of infections, many of which are preventable by vaccination. However, this population is often under-vaccinated because of negligence but also of concerns regarding the safety of these vaccines, the potential risk of exacerbation of underlying disease or vaccine efficacy. In this article, we are trying to stratify different patient groups based on different immunosuppressive treatments and to present adequate vaccination schemes according to the recommendations found in medical literature.

  19. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

    Energy Technology Data Exchange (ETDEWEB)

    Weigel, S.; Kloska, S.; Freund, M. [Dept. of Clinical Radiology, Univ. Hospital of Muenster, Muenster (Germany); Kehl, H.G. [Dept. of Pediatric Cardiology, Univ. Hospital of Muenster, Muenster (Germany)

    2003-12-01

    A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

  20. Immunosuppressive therapy in patients with aplastic anemia: a single-center retrospective study.

    Directory of Open Access Journals (Sweden)

    Hasan Jalaeikhoo

    Full Text Available Aplastic anemia (AA is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.Patients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA were treated with cyclosporine (CsA and danazol while patients with severe AA (SAA as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.Among the 63 studied patients, 29 (46% had NSAA and 34 (54% had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01. The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.This long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.

  1. Autoimmune Thyroid Diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH-Receptor Immune Response

    Directory of Open Access Journals (Sweden)

    Mario Rotondi

    2017-09-01

    Full Text Available Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of active relapsing-remitting multiple sclerosis (MS. Alemtuzumab induces a rapid and prolonged depletion of lymphocytes from the circulation, which results in a profound immuno-suppression status followed by an immune reconstitution phase. Secondary to reconstitution autoimmune diseases represent the most common side effect of Alemtuzumab treatment. Among them, Graves’ disease (GD is the most frequent one with an estimated prevalence ranging from 16.7 to 41.0% of MS patients receiving Alemtuzumab. Thyrotropin (TSH receptor (R-reactive B cells are typically observed in GD and eventually present this autoantigen to T-cells, which, in turn, secrete several pro-inflammatory cytokines and chemokines. Given that reconstitution autoimmunity is more frequently characterized by autoantibody-mediated diseases rather than by destructive Th1-mediated disorders, it is not surprising that GD is the most commonly reported side effect of Alemtuzumab treatment in patients with MS. On the other hand, immune reconstitution GD was not observed in a large series of patients with rheumatoid arthritis treated with Alemtuzumab. This negative finding supports the view that patients with MS are intrinsically more at risk for developing Alemtuzumab-related thyroid dysfunctions and in particular of GD. From a clinical point of view, Alemtuzumab-induced GD is characterized by a surprisingly high rate of remission, both spontaneous and after antithyroid drugs, as well as by a spontaneous shift to hypothyroidism, which is supposed to result from a change from stimulating to blocking TSH-receptor antibodies. These immune and clinical peculiarities support the concept that antithyroid drugs should be the first-line treatment in Alemtuzumab-induced Graves’ hyperthyroidism.

  2. Immunosuppression and reconstitution with thymosin after radiation therapy

    International Nuclear Information System (INIS)

    Wara, W.M.; Wara, D.W.; Ammann, A.J.; Barnard, J.L.; Phillips, T.L.

    1979-01-01

    Since 1976, 102 patients with advanced squamous cell carcinoma, (82, head and neck; 20, esophagus), have been evaluated before receiving irradiation and thymosin fraction 5 therapy at the University of California, San Francisco (UCSF). Thymosin fraction 5 is a mixture of at least 20 polypeptides which has been shown to have immune enhancing capabilities in primary immunodeficiency disease and various malignancies. Immunity prior to treatment (measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells and quantitative serum immunoglobulins) was comparable and normal in the 80 control patients and the 22 thymosin treated patients. Postirradiation significant depression (p<0.01) was demonstrated in cellular immunity in both groups of patients with decreased T and B cell numbers and depressed PHA and MLC stimulation. To date there have been an equal number of recurrences and deaths in both groups of patients

  3. Are Steroids a Beneficial Adjunctive Therapy in the Immunosuppressed Patient with Herpes Simplex Virus Encephalitis?

    Directory of Open Access Journals (Sweden)

    Karlo J. Lizarraga

    2013-03-01

    Full Text Available Few reports describe the reactivation of latent herpes simplex virus causing encephalitis (HSVE in patients undergoing brain radiation therapy and a concomitant steroid regimen. The role for steroid use in the treatment of patients with HSVE has not been fully elucidated. We report the case of a female patient immunosuppressed by steroids and brain radiation who developed HSVE and responded to acyclovir and dexamethasone.

  4. Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation

    Directory of Open Access Journals (Sweden)

    Catić-Đorđević Aleksandra

    2017-01-01

    Full Text Available Immunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection as well as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients’ quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized. Therapeutic drug monitoring (TDM for immunosuppressive drugs is an essential, but at the same time insufficient tool due to low predictability of drug exposition and marked pharmacokinetic variability. Parallel therapeutic, biochemical and clinical monitoring may successfully optimize and individualize therapy for transplanted recipients, providing optimal medical outcomes. Modern pharmacotherapy management should include new biomarkers with better sensitivity and specificity that can identify early cell damage. The aim of this study was to point out the importance of finding new biomarkers that would enable early detection of adverse drug events and cell damage in organ transplant recipients. We wanted to confirm the importance of routine biochemical monitoring in improving the safety of immunosuppressive treatment.

  5. Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent

    Science.gov (United States)

    Qi, Guoyan; Liu, Peng; Dong, Huimin; Gu, Shanshan; Yang, Hongxia; Xue, Yinping

    2017-01-01

    Background Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. Material/Methods MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. Results Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. Conclusions The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma. PMID:28278141

  6. Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent.

    Science.gov (United States)

    Qi, Guoyan; Liu, Peng; Dong, Huimin; Gu, Shanshan; Yang, Hongxia; Xue, Yinping

    2017-03-09

    BACKGROUND Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. MATERIAL AND METHODS MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. RESULTS Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. CONCLUSIONS The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma.

  7. Alemtuzumab

    DEFF Research Database (Denmark)

    Illés, Zsolt; Sejbaek, Tobias; Csépány, Tünde

    2015-01-01

    - and antibody-mediated cytotoxicity. Based on phase 2 and 3 clinical trials, alemtuzumob decreases the risk of sustained neurological deficit and progression compared to high-dose subcutaneous interferon-β1a in patients with active relapsing-remitting MS, either treatment-naïve or with breakthrough disease. We...

  8. Does Pre-Operative Multiple Immunosuppressive Therapy Associate with Surgical Site Infection in Surgery for Ulcerative Colitis.

    Science.gov (United States)

    Uchino, Motoi; Ikeuchi, Hiroki; Bando, Toshihiro; Hirose, Kei; Hirata, Akihiro; Chohno, Teruhiro; Sasaki, Hirofumi; Takahashi, Yoshiko; Takesue, Yoshio; Hida, Nobuyuki; Hori, Kazutoshi; Nakamura, Shiro

    2015-01-01

    Almost all surgeries for ulcerative colitis (UC) are performed under immunosuppressive conditions. Immunomodulators or biologics, with the exception of corticosteroids, do not appear to be risk factors for post-operative infectious complications. However, many patients are on multiagent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressives on the occurrence of surgical site infection (SSI) in UC. We reviewed surveillance data from 181 patients who underwent restorative proctocolectomy between January 2012 and March 2014. The incidences of SSI and the possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. The incidence of incisional (INC) SSI was 13.3% and that of organ/space (O/S) SSI was 7.2%. The number of immunosuppressives did not significantly correlate with each incidence. Total prednisolone administration ≥12,000 mg (OR 2.6) and an American Society of Anesthesiologists score ≥3 (OR 2.8) were shown to be independent risk factors for overall SSI, whereas corticosteroid use in INC SSI (OR 17.4) and severe disease (OR 5.2) and a large amount of blood loss (OR 3.9) in O/S SSI were identified as risk factors. Although a correlation between multiple immunosuppressive therapy and SSIs was not found, it is not recommended that all patients be treated with multiple immunosuppressive therapy. Treatment strategy should be applied based on the patient's condition. © 2015 S. Karger AG, Basel.

  9. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

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    Adam Gassas

    2011-01-01

    Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

  10. Candidal carriage predicts candidiasis during topical immunosuppressive therapy: a preliminary retrospective cohort study.

    Science.gov (United States)

    Tejani, Sara; Sultan, Ahmed; Stojanov, Ivan; Woo, Sook-Bin

    2016-10-01

    To determine (1) the prevalence of candidal carriage in patients with oral mucosal disease to be treated with topical immunosuppressive therapy, and (2) the incidence of oral candidiasis among carriers and noncarriers after initiation of therapy to assess any correlation between carriage and the development of candidiasis. Records of patients who underwent swab cultures for Candida between January 2009 and October 2014 at the Brigham and Women's Hospital in Boston, Massachusetts, were retrospectively reviewed. The prevalence of candidal carriage and incidence of candidiasis were determined by using descriptive statistics. Of 99 evaluable patients, 20 (20.2%) were Candida positive and 79 (79.8%) were Candida negative. Of 44 patients with follow-up, 7 (15.9%) were Candida positive and 37 (84.1%) were Candida negative; five (11.4%) developed candidiasis. Four of seven (57.1%) Candida-positive patients developed candidiasis, whereas only one of 37 (2.7%) Candida-negative patients developed candidiasis (P = .0012). The overall prevalence of candidal carriage was low (20.2%), and there was a significant difference in the incidence of candidiasis between carriers and noncarriers (P = .0012) after topical immunosuppressive therapy. Therefore, patients who are candidal carriers should be monitored closely for the development of secondary candidiasis and may be candidates for prophylactic antifungal therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Monitoring Disease Activity in Patients with Aortitis and Chronic Periaortitis Undergoing Immunosuppressive Therapy by Perfusion CT.

    Science.gov (United States)

    Bier, Georg; Kurucay, Mustafa; Henes, Jörg; Xenitidis, Theodoros; Preibsch, Heike; Nikolaou, Konstantin; Horger, Marius

    2017-04-01

    To evaluate the role of perfusion CT for monitoring inflammatory activity in patients with aortitis and chronic periaortitis undergoing immunosuppressive therapy. Seventeen symptomatic patients (median age 68.5 years) who underwent perfusion-based computed tomography (CT) monitoring after diagnostic contrast-enhanced CT were retrospectively included in this study. Blood flow (BF), blood volume (BV), volume transfer constant (k-trans), time to peak, and mean transit time were determined by setting circular regions of interest in prominently thickened parts of the vessel wall or perfused surrounding tissue at sites where the perfusion CT color maps showed a maximum BF value. Differences in CT perfusion and, morphological parameters, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were tested for significance during therapy. In all patients BF and BV dropped at second perfusion CT (P perfusion CT parameters in aortitis and chronic periaortitis undergoing immunosuppressive therapy dropped at different extent after therapy. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  12. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China.

    Science.gov (United States)

    Xue, Yu; Jiang, Li; Wan, Wei-Guo; Chen, Yu-Ming; Zhang, Jiong; Zhang, Zhen-Chun

    2016-02-05

    Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China. Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis. One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P 1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells), presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with

  13. Knowledge-based immunosuppressive therapy for kidney transplant patients--from theoretical model to clinical integration.

    Science.gov (United States)

    Seeling, Walter; Plischke, Max; de Bruin, Jeroen S; Schuh, Christian

    2015-01-01

    Immunosuppressive therapy is a risky necessity after a patient received a kidney transplant. To reduce risks, a knowledge-based system was developed that determines the right dosage of the immunosuppresive agent Tacrolimus. A theoretical model, to classify medication blood levels as well as medication adaptions, was created using data from almost 500 patients, and over 13.000 examinations. This model was then translated into an Arden Syntax knowledge base, and integrated directly into the hospital information system of the Vienna General Hospital. In this paper we give an overview of the construction and integration of such a system.

  14. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis: a retrospective analysis.

    Science.gov (United States)

    Fang, Jing; Li, Wenge; Peng, Xiangxin; Tan, Zhao; Tan, Min; Zhang, Cong; Wang, Wenbo; Xu, Zhihong; Zhou, Gumin

    2017-03-01

    The aim of this study is to investigate the prevalence and risk factors for hepatitis B virus (HBV) reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis. We performed a retrospective study of 745 HBsAg-negative/HBcAb-positive patients undergoing immunosuppressive therapy for glomerulonephritis from years 2003 to 2012 at the department of nephrology, China-Japan Friendship Hospital, Beijing, China. The patients were divided into HBV reactivation group (n = 27) and non-HBV reactivation group (n = 718). The prevalence of HBV reactivation in patients receiving immunosuppressive therapy for glomerulonephritis was up to 3.62% in serological status of HBsAg-negative/HBcAb-positive. HBV reactivation was associated with several findings: greater proportion of lupus nephritis (25.93 vs. 9.61%, p = 0.014), much higher percentage of HBsAb-negative (74.07 vs. 23.82%, p HBcAb-positive glomerulonephritis patients treated with immunosuppressant, and the prevalence was up to 3.62%. Patients with serological status of HBsAb-negative, more than 1 year of immunosuppressive therapy, and combined immunosuppressant are independent risk factors for HBV reactivation.

  15. Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

    Science.gov (United States)

    Pranteda, G; Carlesimo, M; Bottoni, U; Di Napoli, A; Muscianese, M; Pimpinelli, F; Cordiali, P; Laganà, B; Pranteda, G; Di Carlo, A

    2014-01-01

    A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. © 2014 Wiley Periodicals, Inc.

  16. EFFICACY OF THE IMMUNOSUPPRESSIVE THERAPY AGAINST THE NEPHROTIC SYNDROME AMONG CHILDREN

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    A.G. Timofeeva

    2007-01-01

    Full Text Available The researchers evaluated the efficacy of different immunosuppressive medications in case of steroid dependent and steroid resistant variants of the nephrtic syndrome among children: traditional alkylating agents (cyclophosphamide, chlorbutin, cyclosporine and mycophenolate mofetil. Cyclosporine proved to be most efficient in treatment against steroid dependent nephritic syndrome, as the researchers were more often able to cancel the steroids, while the recurrence of the nephritic syndrome developed less often. In the event of the steroid resistant nephritic syndrome, the full/partial remission was achieved among more than 80% patients also treated by cyclosporine. In case of the proliferating forms of the steroid resistant nephritic syndrome, the positive outcome was achieved among all the children under observation, if mycophenolate mofetil and steroids were further applied. Therapy by the conventional alkylating agents (cyclophosphamide, chlorbutin proved to be less efficient both for the relief from the steroid dependence and persistent remission of the steroid resistant nephritic syndrome.Key words: nephritic syndrome, immunosuppressive therapy, alkylating agents, cyclosporine, mycophenolate mofetil, children.

  17. Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy.

    LENUS (Irish Health Repository)

    Marsh, E A

    2010-06-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

  18. Side Effects of Transplant Immunosuppressive Therapy in Post Renal Transplant Recipients, Mazandaran, Northern Iran

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    Abazar Akbarzadeh Pasha

    2017-04-01

    Full Text Available Background Post-kidney transplant survival relies on patient adherence to the intake of immunosuppressive medication. This study was performed to investigate complications associated with immunosuppressive therapy in renal transplantation. Methods This cross-sectional study was conducted on 188 transplanted patients in Shahid Beheshti hospital of Babol in 2013. Check list and demographic questionnaire for data collecting were used. Then the data using were analyzed in SPSS.18 software by using chi-square test. Results A total of 188 transplanted patients, 115 (61.2% was male and mean age was 12.9 ± 42.9 years. 181 (96.3% of the subjects had at least one complication. The most common complication in 142 cases (75.5% was “excessive hair growth” and after this complication “increased blood sugar” had higher frequency and 119 (63.3% had this complication. Severe form of gingival overgrowth in women was significantly that more than men (22 (30.1, 14 (12.2, P = 0.004, and the other side effect was not significant difference between men and women or different age groups (P > 0.05 Conclusions Finding show that nearly all transplanted recipients suffered from one complication which need to recognize, control and treatment. It suggested that period visiting for early diagnosis and education to patient was recommend.

  19. Comparative efficacy of alemtuzumab and established treatment in the management of multiple sclerosis

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    Babij R

    2015-05-01

    Full Text Available Rachel Babij, Jai S Perumal Department of Neurology, Weill Cornell Medical College, New York, NY, USA Abstract: Alemtuzumab is the newest disease-modifying therapy approved for the treatment of relapsing multiple sclerosis. Alemtuzumab is an anti-CD52 targeted antibody that causes lysis of T and B lymphocytes, monocytes, natural killer cells, macrophages, and dendritic cells. Following its administration, a prolonged T-cell lymphopenia results with emergence of a reconstituted immune system that differs in its composition from that pretreatment. In clinical trials, alemtuzumab has shown impressive efficacy with regard to clinical and radiological outcomes in relapsing multiple sclerosis, along with sustained long-term beneficial effects, and it is attractive for its once-yearly administration. Despite this, the occurrence of serious secondary autoimmune disorders, infections, and a potential risk of malignancy necessitates a careful evaluation of risks versus benefits for an individual patient prior to its use. The requirement of patient commitment to the intense mandatory monitoring program is also a factor to be considered when incorporating alemtuzumab into the treatment regimen. Keywords: alemtuzumab, multiple sclerosis, comparative efficacy

  20. Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study.

    Science.gov (United States)

    Yates, William B; Vajdic, Claire M; Na, Renhua; McCluskey, Peter J; Wakefield, Denis

    2015-02-01

    To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy. A single-center, retrospective cohort study. We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents. Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type. Risk of malignancy relative to the general population and within the cohort. During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed. Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy

  1. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

    Science.gov (United States)

    Kalincik, Tomas; Brown, J William L; Robertson, Neil; Willis, Mark; Scolding, Neil; Rice, Claire M; Wilkins, Alastair; Pearson, Owen; Ziemssen, Tjalf; Hutchinson, Michael; McGuigan, Christopher; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Alroughani, Raed; Pucci, Eugenio; Sola, Patrizia; Hupperts, Raymond; Lechner-Scott, Jeannette; Terzi, Murat; Van Pesch, Vincent; Rozsa, Csilla; Grand'Maison, François; Boz, Cavit; Granella, Franco; Slee, Mark; Spitaleri, Daniele; Olascoaga, Javier; Bergamaschi, Roberto; Verheul, Freek; Vucic, Steve; McCombe, Pamela; Hodgkinson, Suzanne; Sanchez-Menoyo, Jose Luis; Ampapa, Radek; Simo, Magdolna; Csepany, Tunde; Ramo, Cristina; Cristiano, Edgardo; Barnett, Michael; Butzkueven, Helmut; Coles, Alasdair

    2017-04-01

    Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], pmultiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly

  2. Autoimmune Hepatitis: Progress from Global Immunosuppression to Personalised Regulatory T Cell Therapy

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    Nwe Ni Than

    2016-01-01

    Full Text Available Autoimmune hepatitis (AIH is an immune mediated liver injury. The precise aetiology of AIH is still unknown but current evidence suggests both genetic and environmental factors are involved. Breakdown in peripheral self-tolerance, and impaired functions of FOXP3+ regulatory T cell along with effector cell resistance to suppression at the tissue level seem to play an important role in AIH immunopathogenesis. AIH is predominantly a T lymphocytes driven disease but B lymphocytes are also involved in the immunopathology. Innate immune cells are crucial in the initial onset of disease and their response is followed by adaptive T (Th1, Th17, and cytotoxic T cells and B cell responses evidenced by liver histology and peripheral blood serology. Standard treatment regimens involving steroid and immunosuppressive medications lead to global immune suppression requiring life-long therapy with many side effects. Biologic therapies have been attempted but duration of remission is short-lived. Future direction of diagnosis and treatment for AIH should be guided by “omics” and the immunology profile of the individual patient and clinicians should aim to deliver personalised medicine for their patients. Cell therapy such as infusion of autologous, antigen-specific, and liver-homing regulatory T cells to restore hepatic immune tolerance may soon be a potential future treatment for AIH patients.

  3. Hypoxia-driven immunosuppression: a new reason to use thermal therapy in the treatment of cancer?

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    Lee, Chen-Ting; Mace, Thomas; Repasky, Elizabeth A

    2010-01-01

    Hypoxia within the tumour microenvironment is correlated with poor treatment outcome after radiation and chemotherapy, and with decreased overall survival in cancer patients. Several molecular mechanisms by which hypoxia supports tumour growth and interferes with effective radiation and chemotherapies are now well established. However, several new lines of investigation are pointing to yet another ominous outcome of hypoxia in the tumour microenvironment: suppression of anti-tumour immune effector cells and enhancement of tumour escape from immune surveillance. This review summarises this important information, and highlights mechanistic data by which hypoxia incapacitates several different types of immune effector cells, enhances the activity of immunosuppressive cells and provides new avenues which help 'blind' immune cells to detect the presence of tumour cells. Finally, we discuss data which indicates that mild thermal therapy, through its physiologically regulated ability to alter vascular perfusion and oxygen tensions within the tumour microenvironment, as well as its ability to enhance the function of some of the same immune effector activities that are inhibited by hypoxia, could be used to rapidly and safely release the tight grip of hypoxia in the tumour microenvironment thereby reducing barriers to more effective immune-based therapies.

  4. The effect of conventional immunosuppressive therapy on cytokine serum levels in pemphigus vulgaris patients.

    Science.gov (United States)

    Mortazavi, Hossein; Esmaili, Nafiseh; Khezri, Somayeh; Khamesipour, Ali; Vasheghani Farahani, Iman; Daneshpazhooh, Maryam; Rezaei, Nima

    2014-06-01

    Pemphigus vulgaris is an autoimmune disease, in which the role of Th17 cytokines needs to be further explored. This study was performed to assess serum levels of three interleukins (IL) required for Th17 differentiation (IL-1β, IL-6 and IL-23) and two specific Th17 cytokines (IL-17 and IL-22) in a group of patients with pemphigus vulgaris, at baseline, 3 weeks and 6 months after treatment. Correlations between anti-desmogleins and cytokines with disease severity as well as the influence of therapy on the above factors were assessed. Forty-three first-admitted pemphigus vulgaris patients with the active disease entered the study, but only 31 completed the study. Forty-five healthy volunteers were recruited as a control group. The patients were treated with conventional immunosuppressive therapy (oral prednisolone and azathioprine). Cytokines and anti-desmogleins were measured, using enzyme-linked immunosorbent assay. General linear model was used to evaluate the changes over time. In patients at baseline, mean serum level of IL-6 was higher, while mean levels of IL-1β and IL-22 were lower than the controls. After 3 weeks of therapy, IL-1β and IL-6 levels showed a decreasing trend, whereas IL-22 showed an increasing trend. Mean anti-desmogleins 1 and 3 values decreased significantly during the time. Anti-desmoglein values were significantly correlated with disease severity. In conclusion, IL-1β and IL-6 could be involved in the pathogenesis of pemphigus vulgaris. The positive trend of IL-22 is a new finding and should be confirmed by further studies.

  5. The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study.

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    Emanuele D'Amico

    Full Text Available Immunosuppressive agents (ISA have been used in multiple sclerosis (MS for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS?We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use.Out of 6,447 MS patients, 2,034 (31.6% were treated with ISA, with Azathioprine being the most frequently used ISA overall. MS patients treated with ISA alone were more frequently affected by the progressive course (both primary and secondary of the disease (RRR 5.82, 95% CI 4.14-8.16, p<0.0001, had higher EDSS (RRR 3.69, 95% CI 2.61-5.21, p<0.0001, higher assignment age (RRR 1.04, 95% CI 1.03-1.06, p<0.0001 than patients treated with only disease modifying drugs (DMDs.Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population.

  6. Pneumocystis pneumonia complicating immunosuppressive therapy in Crohns disease: A preventable problem?

    Science.gov (United States)

    Omer, Omer; Cohen, Patrizia; Neong, Shuet Fong; Smith, Geoffrey V

    2016-07-01

    We report the case of a 76-year-old man who presented with moderate active Crohn's colitis that was refractory to high-dose corticosteroids, mesalazine and 6-mercaptopurine. He subsequently received a trial of infliximab with poor response and was diagnosed with cytomegalovirus (CMV) colitis, improving on antiviral therapy. Three weeks into treatment he developed acute respiratory distress with hypoxaemia and diffuse pulmonary interstitial infiltrates. This was confirmed as Pneumocystis jirovecii on bronchoalveolar lavage. He responded well to treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was subsequently discharged home. Despite the favourable outcome, our case raises the question of whether chemoprophylaxis against opportunistic infections in immunosuppressed patients with inflammatory bowel disease (IBD) is appropriate. There are currently no recommendations on providing chemoprophylaxis against CMV colitis and so we focus on pneumocystis pneumonia (PCP) where wide debate surrounds the use of prophylactic TMP-SMX in HIV-negative patients. Contrasting approaches to chemoprophylaxis against PCP in IBD likely relates to a lack of clear parameters for defining risk of PCP among patient groups. This must be addressed in order to develop universal guidelines that take into account patient-dependent risk factors. Awareness of the severity of PCP among HIV-negative individuals and the current consensus on PCP prophylaxis in IBD must be raised in order to minimise the risk of PCP and drive research in this controversial area.

  7. Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy

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    Foroutan N

    2013-10-01

    Full Text Available Naghmeh Foroutan,1 Hamid R Rasekh,1 Jamshid Salamzadeh,1 Hamid R Jamshidi,1 Mohsen Nafar2 1Department of Pharmacoeconomics and Pharmaceutical Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 2Department of Kidney Transplantation, Urinary Nephrology Research Center (UNRC, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Objectives: The aim of this study was to determine budget impact of conversion from cyclosporine (CsA to sirolimus (SRL in renal transplant therapy (RTT from the perspective of insurance organizations in Iran. Methods: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF, and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. Results: The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. Conclusion: To evaluate the financial consequence of adding mTOR inhibitors to the insurers’ formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with

  8. The effects of nucleoside analogue prophylactic treatment on HBV activation in HBcAb+ patients undergoing immunosuppressive therapy.

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    Liu, H-L; Zhao, Z; Yang, H; Liu, F-F; Liu, Q; Luo, Q; Yuan, Q; Chen, L-M; Zeng, A-Z

    2013-09-01

    We investigated the effects of prophylactic nucleoside analogue treatment on HBV activation in patients with antibodies against core antigen (HBcAb+) patients undergoing immunosuppressive therapy. Patients (113), who were HBcAb+, with various autoimmune diseases, undergoing immunosuppressive therapy, were divided into two groups. The control group, not treated with antivirals, and the prophylactic group, treated with antiviral drugs. The two groups were evaluated for changes in serum biochemical marker (alanine aminotransferase ALT), virological marker (HBV DNA) and for seroconversion. In the control group, the number of patients with an increase in ALT in patients with isolated HBcAb and HBcAb and antibodies against HBsAg (HBsAb +) were five (20.0%) and one (2.8%), respectively (P HBcAb+ subgroup and one case (2.8%) in HBsAb+/HBcAb+ subgroup (P HBcAb+ only population, six patients (24.0%) in the control group had an increase in HBV DNA compared with none in the antiviral prophylactic group (P HBcAb+ in the control group underwent an HBsAg seroconversion when receiving immunosuppressive therapy for 18 months, while none in the antiviral prophylactic group underwent reversion to HBsAg positivity (P = 0.4949). Under immunosuppressive condition, the risk of HBV activation was much higher in patients with HBcAb than in patients with both HBcAb and antibodies to HBsAb group. Antiviral prophylactic therapy could significantly reduce the risk of HBV reactivation. © 2013 John Wiley & Sons Ltd.

  9. Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

    Science.gov (United States)

    Constantiner, Melissa; Rosenthal-Asher, Deborah; Tedla, Fasika; Salifu, Moro; Cukor, Judith; Wyka, Katarzyna; Hartono, Choli; Serur, David; de Boccardo, Graciela; Cukor, Daniel

    2018-03-01

    Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

  10. Efficacy of interventions for adherence to the immunosuppressive therapy in kidney transplant recipients: a meta-analysis and systematic review.

    Science.gov (United States)

    Zhu, Yichen; Zhou, Yifan; Zhang, Lei; Zhang, Jian; Lin, Jun

    2017-10-01

    Immunosuppressive treatment regimens are complex and require ongoing self-management. Medication adherence can be difficult to achieve for several reasons. The current meta-analysis and systematic review investigated whether adherence interventions improved immunosuppressive treatment adherence in kidney transplant recipients. Medline, Cochrane, EMBASE, and Google Scholar were searched until October 17, 2016 using the following search terms: kidney transplantation, compliance, adherence, and immunosuppressive therapy. Randomized controlled trials and two-arm prospective, retrospective, and cohort studies were included. The primary outcomes were adherence rate and adherence score. Eight studies were included with a total for 546 patients. Among participants receiving intervention, the adherence rate was significantly higher than the control group (pooled OR=2.366, 95% CI 1.222 to 4.578, p=0.011). Participants in the intervention group had greater adherence scores than those in the control group (pooled standardized difference in means =1.706, 95% CI 0.346 to 3.065, p=0.014). Sensitivity analysis indicated that findings for adherence rate were robust. However, for adherence score, the significance of the association disappeared after removing one of the studies indicating the findings may have been overly influenced by this one study. Intervention programs designed to increase immunosuppressive adherence in patients with kidney transplant improve treatment adherence. Copyright © 2017 American Federation for Medical Research.

  11. Recognition of Immune Reconstitution Syndrome Necessary for Better Management of Patients with Severe Drug Eruptions and Those under Immunosuppressive Therapy

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    Tetsuo Shiohara

    2010-01-01

    Full Text Available The immune reconstitution syndrome (IRS is an increasingly recognized disease concept and is observed with a broad-spectrum of immunosuppressive therapy-related opportunistic infectious diseases and severe drug eruptions complicated by viral reactivations. Clinical illness consistent with IRS includes tuberculosis, herpes zoster, herpes simples, cytomegalovirus infections and sarcoidosis: thus, the manifestations of this syndrome and diverse and depend on the tissue burden of the preexisting infectious agents during the immunosuppressive state, the nature of the immune system being restored, and underlying diseases of the hosts. Although IRS has originally been reported to occur in the setting of HIV infection, it has become clear that the development of IRS can also be in HIV-negative hosts receiving immunosuppressive agents, such as prednisolone and tumor necrosis factor α inhibitors, upon their reduction and withdrawal. Drug-induced hypersensitivity syndrome, a life-threatening multiorgan system reaction, is another manifestation of the newly observed IRS. Clinical recognition of the IRS is especially important in improving the outcome for diseases with an otherwise life-threatening progenosis. Clinicians should be aware of the implications of IRS and recognize that relieving the symptoms and signs of immune recovery by anti-inflammatory therapies needs to be balanced with anti-microbial therapies aiming at reducing the amplitude and duration of tissue burden of preexisting microbes.

  12. Nanoparticles and direct immunosuppression

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    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  13. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  14. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China

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    Yu Xue

    2016-01-01

    Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL and more frequently immunosuppressants than the asymptomatic group (P 1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

  15. Efficacy and safety of immunosuppressive therapy in the treatment of seronegative hepatitis associated aplastic anemia

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    Chen HF

    2014-09-01

    Full Text Available Hai-Fei Chen,* Bin-Xian Xu, Hong-Shi Shen,* Zheng-Yang Li, Ling-Juan Jin, Jie-Qing Tang, Jing Wang, Jing-Jing Zhu, Long-Mei Qin, Qing-Ya Cui, Yong-Ya Ren, Tian-Qin Wu Department of hematology, 100th hospital of People’s Liberation Army, Suzhou, Jiangsu province, The People’s Republic of China *These authors have contributed equally to this paper Objective: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA (SNHAA and hepatitis B virus (HBV infection complicating AA (HBVAA, and thereby compare the efficacy of immunosuppressive therapy (IST.Methods: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes.Results: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60% of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00, a quicker response to IST (2.5 months versus 4.5 months, P=0.018, a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03, and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively. No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly

  16. Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies

    OpenAIRE

    Calabrese, L H; Zein, N N; Vassilopoulos, D

    2006-01-01

    Understanding of the natural history and basic biology of hepatitis B virus (HBV) has increased greatly in recent years. In view of this, the following are reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic disease population; (b) the risks of HBV reactivation in patients with rheumatic disease undergoing immunosuppression; and (c) potential strategies to manage these risks.

  17. Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels

    DEFF Research Database (Denmark)

    Kamara, David A; Smith, Colette; Ryom, Lene

    2016-01-01

    BACKGROUND: Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear....

  18. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    Science.gov (United States)

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-08-01

    End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations

  19. A chronic renal rejection model with a fully MHC-mismatched rat strain combination under immunosuppressive therapy.

    Science.gov (United States)

    Hanaoka, Kaori; Kawato, Yuka; Kubo, Kaori; Nakanishi, Tomonori; Maeda, Masashi; Nakamura, Koji; Hirose, Jun; Noto, Takahisa; Fukahori, Hidehiko; Fujikawa, Akihiko; Miyoshi, Sosuke; Takakura, Shoji; Morokata, Tatsuaki; Higashi, Yasuyuki

    2016-09-01

    The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes (MHCs) are critical discrepancies. Here, we established a rat model of chronic rejection using fully MHC-mismatched strains in which kidney disease progresses even under immunosuppressive therapy. LEW (RT1(l)) rats were used as donors and Brown Norway (BN, RT1(n)) rats as recipients. Intramuscular administration of 0.1mg/kg of tacrolimus was initiated on the day of transplantation. Post-transplantation, this dose was maintained until Day 9, suspended until Day 28 and then resumed from Day 29. Renal function, histopathology, and levels of donor-specific antibody (DSA) and several biomarkers of renal injury were assessed. On Day 91 post-transplantation, recipients received tacrolimus treatment with short-term suspension exhibited reduced renal function and changes in histology. Those were characteristics of chronic rejection including glomerulosclerosis, interstitial fibrosis, and tubular atrophy in human transplantation recipients. Urinary protein excretion increased in a linear fashion, and elevated levels of several biomarkers of renal injury and DSA were observed even under administration of an immunosuppressant. We established an allograft rejection model with impaired renal function and typical histopathological changes of chronic rejection in fully MHC-mismatched rats by controlling administration of an immunosuppressant. These findings suggest that this model more accurately reflects transplantation in a clinical setting than existing models and enables the evaluation of therapeutic agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Very late relapse of PTLD 10 yrs after allogeneic HSCT and nine yrs after stopping immunosuppressive therapy

    DEFF Research Database (Denmark)

    Helgestad, Jon; Rosthøj, Steen; Pedersen, Morten Høgild

    2014-01-01

    the fever settled, the PET scan normalized, and the M-component disappeared. Without any ongoing immunosuppressive therapy, PTLD relapsed nine yr later with large intra-abdominal lymph node masses causing ureteric obstruction with bilateral hydronephrosis. Pathological features were identical to the primary...... retroperitoneal tumor occurred one yr after transplantation; a residual tumor infiltrating spleen and colon was resected one yr later. Due to continual pathological signals in liver and lungs, persistent fever, and an M-component in peripheral blood, a new course of four rituximab doses was given, after which...

  1. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998).

    Science.gov (United States)

    Loughran, T P; Zickl, L; Olson, T L; Wang, V; Zhang, D; Rajala, H L M; Hasanali, Z; Bennett, J M; Lazarus, H M; Litzow, M R; Evens, A M; Mustjoki, S; Tallman, M S

    2015-04-01

    Failure to undergo activation-induced cell death due to global dysregulation of apoptosis is the pathogenic hallmark of large granular lymphocyte (LGL) leukemia. Consequently, immunosuppressive agents are rational choices for treatment. This first prospective trial in LGL leukemia was a multicenter, phase 2 clinical trial evaluating methotrexate (MTX) at 10 mg/m(2) orally weekly as initial therapy (step 1). Patients failing MTX were eligible for treatment with cyclophosphamide at 100 mg orally daily (step 2). The overall response in step 1 was 38% with 95% confidence interval (CI): 26 and 53%. The overall response in step 2 was 64% with 95% CI: 35 and 87%. The median overall survival for patients with anemia was 69 months with a 95% CI lower bound of 46 months and an upper bound not yet reached. The median overall survival for patients with neutropenia has not been reached 13 years from study activation. Serum biomarker studies confirmed the inflammatory milieu of LGL but were not a priori predictive of response. We identify a gene expression signature that correlates with response and may be STAT3 mutation driven. Immunosuppressive therapies have efficacy in LGL leukemia. Gene signature and mutational profiling may be an effective tool in determining whether MTX is an appropriate therapy.

  2. EFFICACY OF THE IMMUNOSUPPRESSIVE THERAPY AGAINST THE NEPHROTIC SYNDROME AMONG CHILDREN

    OpenAIRE

    A.G. Timofeeva; T.V. Sergeeva; T.V. Margieva; T.S. Voznesenskaya; O.V. Komarova; A.N. Tsygin

    2007-01-01

    The researchers evaluated the efficacy of different immunosuppressive medications in case of steroid dependent and steroid resistant variants of the nephrtic syndrome among children: traditional alkylating agents (cyclophosphamide, chlorbutin), cyclosporine and mycophenolate mofetil. Cyclosporine proved to be most efficient in treatment against steroid dependent nephritic syndrome, as the researchers were more often able to cancel the steroids, while the recurrence of the nephritic syndrome d...

  3. Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cristina Costa

    2012-03-01

    Full Text Available Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN, possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens: in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0% and 12 (2.0% specimens from 40 (11.0% and 11 (10.4% patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2% and 58 (9.8% specimens from 67 (18.5% and 27 (25.5% patients, being the difference of incidence highly significant (p <0.0001 for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation.

  4. Post-transplant aspergillosis and the role of combined neurosurgical and antifungal therapies under belatacept immunosuppression

    DEFF Research Database (Denmark)

    Ekkehard, Kasper; Bartek, Jiri; Johnson, Jesper Scott

    2011-01-01

    Opportunistic CNS-infection represent a major threat to patients after organ transplantation due to the need for ongoing immunosuppression and belatacept is a novel CTL4A inhibitor, which is increasingly used for patients following cadaveric kidney transplantation. Among the CNS infections...... into our institution in June 2007 with speech difficulties and gait instability 1.5 years after cadaveric kidney transplantation. On imaging, both a mediastinal and left frontal mass were found. Radiographically guided sampling of the mediastinal mass and a stereotactic biopsy of the left frontal brain...

  5. From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Raghavan Chinnadurai

    2013-01-01

    Full Text Available The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS, linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.

  6. From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

    Science.gov (United States)

    Galipeau, Jacques; Nooka, Ajay K.

    2013-01-01

    The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs. PMID:24350294

  7. Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: Report of two cases

    Directory of Open Access Journals (Sweden)

    Reddy I

    2005-01-01

    Full Text Available Disseminated strongyloidiasis is a rare manifestation in patients on immunosuppressive drugs. We report two cases of fatal disseminated Strongyloides stercoralis infestation. The first was in a patient of pemphigus vulgaris who developed an exacerbation of symptoms, one year after diagnosis and was given intravenous dexamethasone and azathioprine and in the third week of hospitalization developed features of septicemia, respiratory failure and petechial hemorrhages which were proven to be due to disseminated strongyloidiasis. The second patient was diagnosed to have stage IV diffuse large cell type of non-Hodgkin lymphoma and after the second cycle of chemotherapy, developed generalized symptoms of septicemia, respiratory failure, purpuric macules and patches. This was also proven to be disseminated strongyloidiasis.

  8. Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help?

    Science.gov (United States)

    Nerini, Erika; Bruno, Fulvio; Citterio, Franco; Schena, Francesco P

    2016-10-01

    End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance.

  9. A case of acute fulminant multiple sclerosis treated with alemtuzumab.

    Science.gov (United States)

    Gobbin, F; Marangi, A; Orlandi, R; Richelli, S; Turatti, M; Calabrese, M; Forgione, A; Alessandrini, F; Benedetti, M D; Monaco, S; Gajofatto, A

    2017-10-01

    We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evaluation of subgingival bacterial plaque changes and effects on periodontal tissues in patients with renal transplants under immunosuppressive therapy.

    Science.gov (United States)

    Saraiva, Luciana; Lotufo, Roberto F M; Pustiglioni, Alessandro N; Silva, Helio T; Imbronito, Ana Vitoria

    2006-04-01

    The purpose of this study was to identify the presence of periodontal microrganisms in 35 renal transplant patients before the transplant procedure. At each time point, clinical parameters were recorded and subgingival plaque samples were collected from 4 different sites at days 30 and 90 after surgery. Samples were plated onto selective and nonselective media to determine total colony counts and the presence of putative periodontal pathogens. After transplant surgery, patients received immunosuppressive therapy. Statistical analysis of the microbiologic data showed significant changes between time points. An increase in total counts of microrganisms was observed on day 90 after surgery. As a side effect of cyclosporine, 14 patients developed gingival overgrowth. Beta-hemolytic Streptococcus was more frequently detected in patients who did not present gingival overgrowth 90 days after surgery. Quantitative and qualitative changes of the subgingival microflora can occur 90 days after transplant surgery, while patients are still under immunosupressive drugs.

  11. Impact of Single Nucleotide Polymorphisms (SNPs on Immunosuppressive Therapy in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Jesus Ruiz

    2015-08-01

    Full Text Available Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA, during the first six months after lung transplantation (51 patients. The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc. The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC. In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%. Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.

  12. An observational study of alemtuzumab following fingolimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Willis, Mark; Pearson, Owen; Illes, Zsolt

    2017-01-01

    OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod then a...

  13. Alemtuzumab-induced elimination of HIV-1-infected immune cells.

    Science.gov (United States)

    Ruxrungtham, Kiat; Sirivichayakul, Sunee; Buranapraditkun, Supranee; Krause, Werner

    2016-01-01

    Currently, there is no drug known that is able to eradicate either HIV or HIV-infected host cells. The effectiveness of all available treatments is based on the prevention of viral replication. We investigated whether the monoclonal, CD52 receptor-targeting antibody, alemtuzumab, which is currently approved for the treatment of multiple sclerosis, is able to eliminate HIV-infected immune cells. In blood samples from healthy donors and from HIV-1-infected subjects who were either treatment-naïve or resistant to HAART, we studied whether the CD52 expression on T cells and their subsets (CD3, CD4, CD8), B cells (CD19), dendritic cells (CD123) and monocytes (CD11c) is retained in HIV-1 infection and whether alemtuzumab is able to eradicate infected cells, using four-colour flow cytometry. We found that CD52 expression on immune cells is retained in HIV-1 infection regardless of CD4 cell count, viral load and treatment status, and is amenable to alemtuzumab-induced depletion. For the first time it could be shown in vitro that HIV-1-infected immune cells can be eliminated by using the monoclonal antibody alemtuzumab.

  14. Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children.

    Science.gov (United States)

    Yagasaki, Hiroshi; Shichino, Hiroyuki; Ohara, Akira; Kobayashi, Ryoji; Yabe, Hiromasa; Ohga, Shouichi; Hamamoto, Kazuko; Ohtsuka, Yoshitoshi; Shimada, Hiroyuki; Inoue, Masami; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kojima, Seiji

    2014-05-01

    Patients with severe aplastic anemia (SAA) and an absolute neutrophil count (ANC) of 0 typically have fatal outcomes. We defined fulminant AA (FAA) as ANC = 0 for at least 2 weeks prior to and after immunosuppressive therapy (IST). We analyzed the outcomes of 35 children with FAA among 288 children who enrolled in a prospective study for AA (AA-97 study). AA was classified as FAA (n = 35), very SAA (vSAA; n = 129), or SAA (n = 124). All of the children received the IST with horse anti-thymocyte globulin (ATG) and cyclosporine (CsA). A significantly lower response rate at 6 months was seen in children with FAA when compared to those with vSAA or SAA (40.0, 63.6, and 63.7 %, respectively; p = 0.027). Of 20 nonresponder patients in the FAA group, 11 were rescued by alternative donor transplantation, and 5 patients showed a late response after 6 months. Consequently, no significant difference was noted in overall survival when comparing the FAA, vSAA, and SAA groups (88.5, 95.8, and 96.8 %). These findings indicate that IST with ATG and CsA is justified as a first-line treatment for children with FAA who lack a human leukocyte antigen-matched sibling donor.

  15. [The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy].

    Science.gov (United States)

    Sun, Ying-xin; Zhu, Ming-qing; He, Guang-sheng; Wang, Xiu-li; Fang, Bao-zhi; Lu, Cong; Liu, Zhen-zhen; Wu, Qian; Yang, Yong; Wu, De-pei; Sun, Ai-ning

    2013-07-01

    To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA). A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyte globulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months. Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values clone was positive or negative. PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurred before or after IST does not affect the therapeutic efficacy.

  16. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  17. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients.

    Science.gov (United States)

    Muduma, Gorden; Shupo, Francis C; Dam, Sophie; Hawken, Natalia A; Aballéa, Samuel; Odeyemi, Isaac; Toumi, Mondher

    2016-01-01

    Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients' non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients' HRQoL because of their side effects and the complex chronic medication regimen they represent. To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients' adherence to IT. Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants' responses. Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the

  18. Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

    Directory of Open Access Journals (Sweden)

    Michaud L

    2016-12-01

    Full Text Available Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20 might have lower medication adherence than noncomplex patients (INTERMED≤20. Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20. Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11 and noncomplex patients (N=21 were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value. Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly

  19. Cyclosporine A-loaded and stem cell-seeded electrospun nanofibers for cell-based therapy and local immunosuppression

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Chudíčková, Milada; Trošan, Peter; Svobodová, Eliška; Krulová, Magdalena; Kubinová, Šárka; Syková, Eva; Širc, Jakub; Michálek, Jiří; Juklíčková, M.; Munzarová, M.; Zajícová, Alena

    2011-01-01

    Roč. 156, č. 3 (2011), s. 406-412 ISSN 0168-3659 R&D Projects: GA AV ČR KAN200520804; GA ČR GAP304/11/0653; GA ČR(CZ) GAP301/11/1568; GA ČR GD310/08/H077; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40500505; CEZ:AV0Z50520514 Keywords : nanofibers * immunosuppression * cell transfer Subject RIV: EC - Immunology Impact factor: 5.732, year: 2011

  20. Alemtuzumab: a review of efficacy and risks in the treatment of relapsing remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Guarnera C

    2017-07-01

    Full Text Available Cristina Guarnera, Placido Bramanti, Emanuela Mazzon Experimental Neurology Laboratory, IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, Messina, Italy Abstract: Alemtuzumab is a selective humanized monoclonal antibody directed against the CD52 antigen, and has been found to be a powerful treatment for relapsing remitting multiple sclerosis. Alemtuzumab demonstrated high efficacy in several clinical studies. The risk of relapse and sustained accumulation of disability showed significant reduction in the Phase II CAMMS223 and the Phase III clinical trials CARE MS I and CARE MS II. The data presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis confirmed these results. After completion of a 1-year treatment cycle, alemtuzumab showed a sustained effect. Although the efficacy of alemtuzumab has been widely proven, several severe adverse effects have been reported with its use. Infusion-associated reactions, increased risk of infections, and secondary autoimmunity have been associated with alemtuzumab. Autoimmune disease – mainly of the thyroid – has been reported. Immune thrombocytopenic purpura and autoimmune nephropathies have been observed less frequently. These adverse effects, given the short period of alemtuzumab marketing for relapsing remitting multiple sclerosis, require strict monitoring. Keywords: effectiveness, clinical studies, follow-up, adverse events

  1. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    Full Text Available The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined.We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group, and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group.A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05. Flagellar motor switch protein (fliNY and type IV pilus assembly protein pilM (pilM were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity.Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

  2. Alemtuzumab in the treatment of multiple sclerosis: patient selection and special considerations

    Directory of Open Access Journals (Sweden)

    Dörr J

    2016-10-01

    Full Text Available Jan Dörr,1,2 Karl Baum1 1Multiple Sclerosis Center, Neurology Department, Klinik Hennigsdorf, Hennigsdorf, 2NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: Multiple sclerosis (MS is among the most common chronic inflammatory diseases of the central nervous system. Although not curable, the constantly increasing armamentarium of disease-modifying drugs now allows control of disease activity in many patients. The humanized monoclonal antibody alemtuzumab is a powerful drug licensed for the treatment of MS. Upon binding to the CD52 surface protein on CD4+ and CD8+ T cells, B cells, and monocytes, circulating CD52+ cells are eliminated via antibody- and complement-mediated lysis, and a less autoreactive adaptive immune system is reconstituted. The efficacy of alemtuzumab in terms of both clinical and magnetic resonance imaging outcomes has been demonstrated in several phase II/III trials including long-term extensions and follow-up studies. Treatment response to alemtuzumab is strongest as long as active inflammation is the predominant pathophysiological feature, and it is becoming less efficacious in neurodegeneration-dominated later stages of the disease. Thus, the optimal placement of alemtuzumab within treatment algorithms of MS is crucial. The impressive efficacy of alemtuzumab is counteracted by a less favorable safety profile. Besides usually manageable infusion-associated side effects, development of secondary autoimmunity in almost half of treated patients is the most disconcerting risk of alemtuzumab. The high frequency, the delayed occurrence, and the potentially severe course of secondary autoimmune diseases require awareness and a close long-term monitoring of patients treated with alemtuzumab. Biomarkers that would allow prediction of treatment response to alemtuzumab on the one hand and identification of patients at risk for the development of secondary autoimmune diseases on

  3. Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

    Science.gov (United States)

    Gorevski, Elizabeth; Succop, Paul; Sachdeva, Jyoti; Cavanaugh, Teresa M; Volek, Paul; Heaton, Pamela; Chisholm-Burns, Marie; Martin-Boone, Jill E

    2013-01-01

    To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients' adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited "low openness" scores were 91% more likely to be nonadherent. Kidney transplant patients' physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients' adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence.

  4. Development and Internal Validation of a Prediction Model to Estimate the Probability of Needing Aggressive Immunosuppressive Therapy With Cytostatics in de Novo Lupus Nephritis Patients.

    Science.gov (United States)

    Restrepo-Escobar, Mauricio; Granda-Carvajal, Paula Andrea; Jaimes, Fabián

    2017-07-18

    To develop a multivariable clinical prediction model for the requirement of aggressive immunosuppression with cytostatics, based on simple clinical record data and lab tests. The model is defined in accordance with the result of the kidney biopsies. Retrospective study conducted with data from patients 16 years and older, with SLE and nephritis with less than 6 months of evolution. An initial bivariate analysis was conducted to select the variables to be included in a multiple logistic regression model. Goodness of fit was evaluated using a Hosmer-Lemeshow test (H-L) and the discrimination capacity of the model by means of the area under the ROC (AUC) curve. Data from 242 patients was gathered; of these, 18.2% (n=44) did not need an addition of cytostatics according to the findings of their kidney biopsies. The variables included in the final model were 24-h proteinuria, diastolic blood pressure, creatinine, C3 complement and the interaction of hematuria with leukocyturia in urinary sediment. The model showed excellent discrimination (AUC=0.929; 95% CI=0.894-0.963) and adequate calibration (H-L, P=.959). In recent-onset LN patients, the decision to use or not to use intensive immunosuppressive therapy could be performed based on our prediction model as an alternative to kidney biopsies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Muduma G

    2016-01-01

    Full Text Available Gorden Muduma,1 Francis C Shupo,2 Sophie Dam,3 Natalia A Hawken,3 Samuel Aballéa,3 Isaac Odeyemi,1 Mondher Toumi4 1Astellas Pharma Europe Ltd, Chertsey, 2Creativ-Ceutical Ltd, London, UK; 3Creativ-Ceutical Ltd, Paris, 4Public Health (EA 3279, Faculty of Medicine, Aix-Marseille University, Marseille, France Background: Renal transplantation (RT is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients’ non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients’ HRQoL because of their side effects and the complex chronic medication regimen they represent. Purpose: To elicit key concepts related to adherence to immunosuppressant therapy (IT and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients’ adherence to IT. Materials and methods: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants’ responses. Results: Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember

  6. Comparison between spousal donor transplantation treated with anti-thymocyte globulin induction therapy and, living related donor transplantation treated with standard immunosuppression

    Directory of Open Access Journals (Sweden)

    Erkan Demir

    2014-01-01

    Full Text Available The worldwide shortage of organs available for transplantation has led to the use of living-unrelated kidney donors. In this context, spouses represent an important source of organ donors. We compared the allograft outcomes of spousal donor transplantation (SDT with anti-thymocyte globulin (ATG induction therapy and living related donor transplantation (LRDT with triple immonosuppression and basiliximab, in addition. Among the 335 living and deceased donor kidney transplantations performed between April 2001 and June 2010, there were 274 living donor kidney transplantations including 34 SDT and 240 LRDT. The minimum follow-up period was 36 months. All recipients of SDT received ATG (1.5 mg/kg induction therapy, which was stopped five to seven days after surgery. Maintenance immunosuppression included tacrolimus (TAC, mycophenolate mofetil (MMF and prednisolone. LRDT recipients received triple immunosuppressive protocol consisting of cyclosporine or TAC, MMF and prednisolone, in addition to basiliximab. There was a significant difference between the two groups in recipient age, while pre-operative duration on dialysis, recipient sex and donor age and sex were not significantly different. There was also a significant difference between the two groups in the number of human leukocyte antigen (HLA mismatches. The 1-, 3- and 5-year graft survival rates of SDT were 94.1%, 88.2% and 79.4%, respectively, and the frequency of acute rejection episodes was 5.8% (two cases. The 1-, 3- and 5-year graft survival rates of LRDT were 95.8%, 91.6% and 83.3%, respectively, with the frequency of acute rejection being 16.2%. The graft survival rates of SDT were as good as LRDT, while the acute rejection rates in SDT were lower than in LRDT, although the difference was not statistically different (P = 0.13.

  7. Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment - an hypothesis

    DEFF Research Database (Denmark)

    Vojdeman, Fie Juhl; Jurlander, Jesper; Van't Veer, Mars

    2013-01-01

    ABSTRACT In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in m...

  8. Immunosuppression – tough ally in torrid time

    Directory of Open Access Journals (Sweden)

    Elżbieta Ograczyk

    2015-12-01

    Full Text Available Immunosuppression is a condition characterized by weakened or inhibited immune response. It occurred both in humoral and cellular response. This is related to the variable levels of deficiency for each antibody class (IgG, IgM, IgA and a decrease in the number and function of immune cells, mainly T cells which results in the inhibition of cytokine production, signaling transduction and clonal expansion. Immunosuppressive therapy is used in many fields of medicine, such as transplantology, oncology, autoimmune disorders. Immunosuppression can be induced in several ways, by the surgical resection of the organs of the immune system, physical methods using X-rays or chemical methods using pharmacological agents. The most common way to induce immunosuppression is the administration of immunosuppressive drugs, amongst others: glucocorticoids, cytostatic drugs, immunophilin-binding agents, monoclonal antibodies. Unfortunately, the desired therapeutic effects of immunosuppression may be accompanied by a number of side effects associated with both impaired immunity (susceptibility to infections, including those caused by opportunistic microorganisms, toxic effects on the tissues (nephrotoxicity, neurotoxicity, or with a direct impact on the processes of malignancy. This harmful influence can be limited by the modification of the existing drugs, looking for new ones or developing new methods for the controlled kinetics of releasing the immunosuppressive pharmaceuticals. The personalization of immunosuppressant treatment according to genetic/genomic characteristics of individual patient represents the quite innovative look into the issue of immunosuppression.

  9. Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

    Directory of Open Access Journals (Sweden)

    Gorevski E

    2013-04-01

    Full Text Available Elizabeth Gorevski,1 Paul Succop,1 Jyoti Sachdeva,1 Teresa M Cavanaugh,1 Paul Volek,1 Pamela Heaton,1 Marie Chisholm-Burns,2 Jill E Martin-Boone1 1University of Cincinnati, Cincinnati, OH, USA, 2University of Tennessee College of Pharmacy, Memphis, TN, USA Objectives: To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. Methods: A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients’ adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. Results: A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited “low openness” scores were 91% more likely to be nonadherent. Kidney transplant patients’ physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. Conclusion: The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence. Keywords: adherence, transplant, liver, kidney

  10. Risk of malignancy in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis under immunosuppressive therapy: a single-center experience.

    Science.gov (United States)

    Fantò, Marta; Peragallo, Mario Stefano; Pietrosanti, Mario; Di Rosa, Roberta; Picchianti Diamanti, Andrea; Salemi, Simonetta; D'Amelio, Raffaele

    2016-02-01

    Systemic inflammatory rheumatic diseases are associated with an increased risk of malignancy, in particular of lymphoproliferative disorders. Chronic inflammation, due to the disease itself, generates a microenvironment able to promote cancer development, but it is still controversial whether immunosuppressive therapy may contribute to carcinogenesis. The aim of the study was to evaluate the risk of malignancy in 399 patients affected by rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis, all treated with either tumor necrosis factor α-inhibitors plus disease-modifying anti-rheumatic drugs (DMARDs) or DMARDs alone. The risk of malignancy in this cohort of patients, observed in the period between 2005 and 2011 at S. Andrea Hospital-Sapienza University of Rome, was compared with that of the general Italian population, matched for age, sex, and area of residence. Fourteen (3.5%) malignancies, five of which were hematologic, have been observed. The overall cancer risk was not significantly increased in comparison to the general population, whereas the risk of hematologic malignancies appeared significantly higher in RA patients (SIR 4.94, 95% CI 1.35-12.64), particularly in female gender (SIR 6.9, 0.95% CI 1.88-17.66). No significant association between therapy and malignancy was demonstrated in RA patients.

  11. Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.

    Science.gov (United States)

    Jeong, Dae Chul; Chung, Nack Gyun; Cho, Bin; Zou, Yao; Ruan, Min; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ohara, Akira; Kosaka, Yoshiyuki; Yang, Wenyu; Kim, Hack Ki; Zhu, Xiaofan; Kojima, Seiji

    2014-04-01

    Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 - 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first-line therapy if horse antithymocyte globulin is not available.

  12. Markedly High Plasma Thrombopoietin (TPO) Level is a Predictor of Poor Response to Immunosuppressive Therapy in Children With Acquired Severe Aplastic Anemia.

    Science.gov (United States)

    Elmahdi, Shaimaa; Muramatsu, Hideki; Narita, Atsushi; Ismael, Olfat; Hama, Asahito; Nishio, Nobuhiru; Okuno, Yusuke; Xu, Yinyan; Wang, Xinan; Takahashi, Yoshiyuki; Kojima, Seiji

    2016-04-01

    Immunosuppressive therapy (IST) is commonly used for patients with acquired severe aplastic anemia (SAA). Because the clinical response rate and therapeutic outcome for individual patients to IST varies, an in vitro test that identifies potential responders would be desirable. We evaluated the relationship between thrombopoietin (TPO) levels at the time of diagnosis and the response to IST at 6 months in 85 children (median age, 9.0 years; range, 1.0-15.5 years) with acquired SAA using enzyme-linked immunosorbent assay. Thirty-one age-matched healthy individuals were used as controls. All patients received antithymocyte globulin and cyclosporine. Overall, 39 patients (45.9%) responded to IST at 6 months. TPO plasma levels were significantly higher in nonresponders than in responders (1,555.8 vs. 1,284.7 pg/ml, respectively; P = 0.031). Multivariate analysis identified the TPO levels of >1,796.7 pg/ml (TPO-high group, 20 patients; odds ratio (OR), 8.285; 95% confidence interval (CI), 2.114-32.904; P = 0.002) as independent poor predictors of IST response at 6 months. Moreover, the TPO-high group was associated with lower 5-year failure-free survival rates (30% vs. 68%, P = 0.012) compared with the TPO-low group. The measurement of TPO levels at diagnosis is useful for predicting the response to IST in children with SAA and may help in decision making. © 2015 Wiley Periodicals, Inc.

  13. Low incidence of lymphoproliferative disease post kidney transplantation with prevalent use of alemtuzumab

    Directory of Open Access Journals (Sweden)

    John Fredy Nieto-Ríos

    2014-01-01

    Full Text Available Introduction: It is well known that the incidence of malignancy is significantly higher in transplanted patients than in general population. The incidence of lymphoproliferative disease post-transplantation (PTLD is approximately of 1% to 2% in kidney transplantation recipients. Objective: The main objective of this study was to evaluate the PTLD incidence when monitoring kidney transplanted patients between the years 2005 and 2010. Methods: Kidney transplanted patients’ data was retrospectively taken between the years 2005 to 2010 in order to determine the number of PTLD cases according to the inductor scheme used. Results: 425 patients were transplanted between 2005 and 2010. They received alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% and thymoglobulin 2.4%. The 7% did not receive antibody induction. During this period 2 cases of PTLD ocurred: One with multiple myeloma and the other with lymphoma. One of them had been treated with alemtuzumab and the other with thymoglobulin. Conclusions: The PTLD incidence in our group, where alemtuzumab was used predominantly as inductor, was very low; this might suggest that alemtuzumab is a medication that does not increase the risk of this kind of neoplasia.

  14. Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands.

    NARCIS (Netherlands)

    Laros, B.A.P. van; Huisman, C.A.; Wijermans, P.W.; Schipperus, M.R.

    2007-01-01

    BACKGROUND: Alemtuzumab (MabCampath) is a monoclonal antibody against CD52, indicated as third-line treatment of chronic lymphocytic leukaemia (CLL). As most important side effect opportunistic infections are mentioned. It is, however, unknown whether these complications often lead to problems in

  15. Lack of evidence of viral reactivation in HBsAg-negative HBcAb-positive and HCV patients undergoing immunosuppressive therapy for psoriasis.

    Science.gov (United States)

    Morisco, Filomena; Guarino, Maria; La Bella, Serena; Di Costanzo, Luisa; Caporaso, Nicola; Ayala, Fabio; Balato, Nicola

    2014-12-19

    HBV and HCV reactivation have been widely reported in patients undergoing immunosuppressive therapy (IT); however, few data are available on the risk of reactivation in patients with psoriasis receiving IT. The aim of our study was to assess the prevalence of HBV and HCV infection in patients with psoriasis and to evaluate the effects of IT during the course of the infection. The study included psoriatic patients who attended an Italian tertiary referral hospital from 2009 to 2012. A total of 224 patients were enrolled. We evaluated: HBV and HCV markers, type of IT and the occurrence of viral reactivation. The observational period ranged from the beginning of IT to the last visit, with a mean follow-up period of 54 months. Two hundred and twenty patients (135 males and 89 females; mean age 59 years; range 18-86 years) with psoriasis, with or without psoriatic arthritis, receiving conventional IT and/or biological drugs were tested for markers of infection. We identified 23/224 patients (10.2%) with isolated positivity for HBcAb positivity, 36/224 (16%) with positivity for HBsAb/HBcAb, and 15/224 (6.6%) with positivity for HCV-Ab. No patient was HBsAg positive, none of them underwent pre-emptive therapy with lamivudine or other antiviral drugs and no one showed episodes of viral reactivation. The prevalence of HBsAg in patients with psoriasis is lower than that observed in the general population. The prevalence of isolated positivity for HBcAb and of combined positivity for HBcAb and HBsAb is 10.2% and 16%, respectively. The prevalence of HCV infection (HCV-RNA+) is 4%. In patients with psoriasis and HCV-Ab or HBcAb positivity, the IT seems to be safe, regardless of the type of drugs.

  16. Alemtuzumab in Multiple Sclerosis: Lessons from Social Media in Enhancing Patient Care.

    Science.gov (United States)

    Rath, Louise; Vijiaratnam, Nirosen; Skibina, Olga

    2017-01-01

    Alemtuzumab is a monoclonal antibody that has been approved for the treatment of relapsing-remitting multiple sclerosis (MS). Alemtuzumab is associated with infusion reactions and potential autoimmune complications. Patient education and understanding are crucial to favorable outcomes. Our objective was to observe communication on a peer-to-peer Facebook group for content, accuracy of posts, and number of "likes" per post and to compare shared themes to current approved prescribing information and educational modules. We identified a Facebook group specific to alemtuzumab in MS. A 14-day window was observed. Posts were classified as "sharing" or "seeking information." Content analysis was used for information-seeking posts. Accuracy of replies was compared with product prescribing information. We reviewed 458 posts. Members contemplating receiving or currently receiving alemtuzumab primarily used Facebook for information gathering (54.6%), followed by seeking emotional support and sharing personal experiences (45.4%). Most shared experiences (83.6%) were positive. Themes for information were predominantly consistent with standard protocols. Complications discussed included infection (15.50%), bone pain (11.80%), immune thrombocytopenia (8.07%), and fatigue (7.46%). Accuracy of replies was consistent with product information except for immune thrombocytopenia. Some patients with MS look to online groups for discussion, peer support, and information. Although written guidelines on the studied home page reinforce that online discussion "does not replace medical advice," inaccurate information does occur. Health-care providers' reviews of these online sites allow insight into the real-world experiences of patients receiving alemtuzumab, with potential for modification of educational approaches by health-care professionals.

  17. Selective immunosuppression by radiation

    International Nuclear Information System (INIS)

    Chanana, A.D.; Cronkite, E.P.; Joel, D.D.

    1976-01-01

    The historical aspects of selective irradiation of lymphocytes are reviewed as well as the problems concerned with dosimetry and the radiosensitivity of circulating blood elements other than lymphocytes. The possibilities of perturbations in steady-state lymphocytopoiesis which might be triggered by products of radiation-induced cell death are presented; however, the parameters investigated thus far, such as the degree of lymphocytopenia, thoracic duct lymphocyte output, and cell-cycle times of thoracic duct lymphocytes, have failed to reveal any such perturbations. Studies in adrenalectomized calves have failed to confirm the notion that lymphocytopenia after extracorporeal irradiation of blood and lymph might primarily be accounted for by stress-induced corticosteroid hormonal activity. Of the various techniques, only local-graft irradiation and extracorporeal irradiation of blood (ECIB) have found clinical application. The results obtained are encouraging and indicate a need for additional, well-controlled clinical trials, especially concerning the role of ECIB as an adjunct to standard immunosuppressive therapy. The experimental results with extracorporeal irradiation of lymph have also established the potential of this technique for clinical application. There is an urgent need for studying the influence of irradiation on various subpopulations of lymphocytes with regard to their functional capabilities and in particular with regard to their reproductive potential. Possible influence of selective blood irradiation on circulating stem cells in blood needs to be evaluated

  18. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy.

    Science.gov (United States)

    van Doesum, Willem B; Gard, Lilli; Bemelman, Frederike J; de Fijter, Johan W; Homan van der Heide, Jaap J; Niesters, Hubert G; van Son, Willem J; Stegeman, Coen A; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F

    2017-06-01

    It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy (BKVAN). From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) (P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group (P=.03). Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Future direction of immunosuppression in lung transplantation.

    Science.gov (United States)

    Afshar, Kamyar

    2014-12-01

    Immunosuppression regimens have helped improve rejection episodes following lung transplantation, but long-term outcomes are still not comparable with cardiac, hepatic, or renal transplantation. This review summarizes the immunobiology that contributes to rejection events and future opportunities in outcomes on the basis of providing optimized delivery of the immunosuppression based on immune-monitoring techniques, taking into account individual patient pharmacokinetics and phenotypic variance. Drug toxicities, narrow therapeutic drug monitoring windows, and current immunoassays currently do not assist in detecting the global degree of immunosuppression. The currently available randomized control trials for induction therapy or maintenance therapies do not provide additional benefits compared with previously reported retrospective trials. To push beyond the current barriers, transplant teams are focusing on the role of pharmacokinetics, assessing phenotypic variable to potentially modify to quadruple therapy and using extracorporeal photopheresis. Conventional practice for the choices of immunosuppression is being evaluated on the basis of randomized control trials as opposed to retrospective studies or single-center trials. The future direction of immunosuppression will be continued by dynamic processes taking into consideration measures to improve tolerance, reducing treatment burden, and providing the best level of evidence while accounting for rejection, infections, renal function, and other comorbidities.

  20. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    Science.gov (United States)

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. © 2014 Wiley Periodicals, Inc.

  1. Management of HBV Infection During Immunosuppressive Treatment

    OpenAIRE

    Marzano, Alfredo

    2009-01-01

    The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), b) the treatment with antivirals (therapy) of active carriers, c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if...

  2. Dogs, zoonoses and immunosuppression.

    Science.gov (United States)

    Robinson, R A; Pugh, R N

    2002-06-01

    Dogs are the source of a wide range of zoonotic infections that pose a significant threat to human health. This is particularly the case for immunocompromised people, although there are few robust studies that determine immunosuppression as a risk factor for transmission of zoonoses from dogs to humans. An increasing proportion of human society is immunodeficient, principally through the advent of HIV infection and through more people, particularly the expanding elderly group, being subjected to immunosuppressive agents. This is happening at a time when more such people are capitalizing on the acknowledged benefits of dog ownership, making for a potentially dangerous mix. Enteric pathogens (for example, Salmonella, Campylobacter and Cryptosporidium species, that may be canine derived) are a frequent risk to the health of immunocompromised persons. Veterinarians and physicians can be criticised for not communicating with each other, and for not providing adequate risk assessment to pet owners. There is scope for voluntary groups to provide information and support for the immunosuppressed who wish to keep their dogs. Key recommendations are to maintain a clean personal environment and intact mucocutaneous barriers. Public health professionals could help rectify the current communications gap between veterinary and medical staff and so facilitate in the appropriate management of dog-owning immunocompromised people.

  3. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia.

    Science.gov (United States)

    Parikh, Sameer A; Keating, Michael J; O'Brien, Susan; Wang, Xuemei; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Estrov, Zeev; Badoux, Xavier; Lerner, Susan; Wierda, William G

    2011-08-25

    Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation.

  4. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy

    NARCIS (Netherlands)

    van Doesum, Willem B.; Gard, Lilli; Bemelman, Frederike J.; de Fijter, Johan W.; van der Heide, Jaap J. Homan; Niesters, Hubert G.; van Son, Willem J.; Stegeman, Coen A.; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F.

    Background: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). Methods: A prospective, multicenter, open-label

  5. Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy

    NARCIS (Netherlands)

    van Doesum, Willem B.; Gard, Lilli; Bemelman, Frederike J.; de Fijter, Johan W.; Homan van der Heide, Jaap J.; Niesters, Hubert G.; van Son, Willem J.; Stegeman, Coen A.; Groen, Henk; Riezebos-Brilman, Annelies; Sanders, Jan Stephan F.

    2017-01-01

    Background: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). Methods: A prospective, multicenter, open-label

  6. Need for optimized immunosuppression in elderly kidney transplant recipients.

    Science.gov (United States)

    Lehner, L J; Staeck, Oliver; Halleck, Fabian; Liefeldt, Lutz; Bamoulid, Jamal; Budde, K

    2015-10-01

    The proportion of elderly kidney transplant candidates is increasing worldwide due to higher number of patients with end-stage renal disease in aging societies. Accordingly, organ allocation policies in this population were adjusted in several countries. The European Senior Program is the most prominent example, where elderly patients (≥65years) receive elderly (≥65years) donor organs with acceptable results. Because of age-dependent changes in the immune response and higher susceptibility to immunosuppressant side effects, outcomes in elderly patients are different compared to younger kidney transplant recipients. However, elderly patients do reject, especially poorly matched elderly donor organs. This warrants tailored immunosuppressive regimes with regard to the age-related changes of the immune system. Rejection therapies may have detrimental side effects in the seniors and are frequently leading to over-immunosuppression (malignancy and infections) in long-term therapy. It is hypothesized that after initial graft adaptation elderly patients may benefit from less immunosuppression in order to lower cancer risk and reduce infection rates and cardiovascular comorbidities. Current evidence on recommended standard immunosuppressive therapy was mainly derived from trials, where elderly patients were excluded or only a minority. In order to improve immunosuppressive therapy in elderly transplant recipients, current immunosuppressive regimes have to be re-investigated in this growing population. Up to date, only a few well-designed prospective studies were performed in elderly populations and demonstrate the need for effective immunosuppression in the first months after transplantation. It is evident that novel treatment strategies and adequately powered prospective clinical trials are needed to establish time-adapted immunosuppressive regimens according to the needs of this vulnerable group of kidney transplant recipients. Copyright © 2015 Elsevier Inc. All

  7. Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation - A systematic review of randomized trials, observational studies and case reports.

    Science.gov (United States)

    Croce, Evelina; Hatz, Christoph; Jonker, Emile F; Visser, L G; Jaeger, Veronika K; Bühler, Silja

    2017-03-01

    Live vaccines are generally contraindicated on immunosuppressive therapy due to safety concerns. However, data are limited to corroborate this practice. To estimate the safety of live vaccinations in patients with immune-mediated inflammatory diseases (IMID) or solid organ transplantation (SOT) on immunosuppressive treatment and in patients after bone-marrow transplantation (BMT). A search was conducted in electronic databases (Cochrane, Pubmed, Embase) and additional literature was identified by targeted searches. Randomized trials, observational studies and case reports. Patients with IMID or SOT on immunosuppressive treatment and BMT patients vaccinations: mumps, measles, rubella (MMR), yellow fever (YF), varicella vaccine (VV), herpes zoster (HZ), oral typhoid, oral polio, rotavirus, Bacillus Calmette-Guérin (BCG), smallpox. One author performed the data extraction using predefined data fields. It was cross-checked by two other authors. 7305 articles were identified and 64 articles were included: 40 on IMID, 16 on SOT and 8 on BMT patients. In most studies, the administration of live vaccines was safe. However, some serious vaccine-related adverse events occurred. 32 participants developed an infection with the vaccine strain; in most cases the infection was mild. However, in two patients fatal infections were reported: a patient with RA/SLE overlap who started MTX/dexamethasone treatment four days after the YFV developed a yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and died. The particular vaccine lot was found to be associated with a more than 20 times risk of YEL-AVD. One infant whose mother was under infliximab treatment during pregnancy received the BCG vaccine at the age of three months and developed disseminated BCG infection and died. An immunogenicity assessment was performed in 43 studies. In most cases the patients developed satisfactory seroprotection rates. In the IMID group, YFV and VV demonstrated high seroconversion rates

  8. In vivo T-cell depletion using alemtuzumab in family and unrelated donor transplantation for pediatric non-malignant disease achieves engraftment with low incidence of graft vs. host disease.

    Science.gov (United States)

    Saif, M A; Borrill, R; Bigger, B W; Lee, H; Logan, A; Poulton, K; Hughes, S; Turner, A J; Bonney, D K; Wynn, R F

    2015-03-01

    In vivo T-cell depletion, using alemtuzumab therapy prior to SCT, can reduce the incidence of GVHD. This treatment has a potential to delay immune reconstitution resulting in increased morbidity due to viral illnesses. We retrospectively analyzed data on all pediatric patients with non-malignant disorders who received alemtuzumab-based conditioning regimens in our center over the last 10 yr (n = 91). Our data show an OS of 91.2%. The incidence of acute (grade 2-4) GVHD was 18.7% and that of chronic GVHD 5.5%. Viremia due to adenovirus, EBV and CMV was seen in 19.8%, 64.8% and 39.6% patients, respectively, with only two deaths attributed to viral infection (adenovirus). Chimerism level at three month was predictive of graft outcome. Nine patients, who had graft failure after first SCT, were salvaged with a second SCT using RIC and same donor (if available). Based on these results, we conclude that the use of in vivo T-cell depletion is safe, achieves good chimerism and does not lead to increased morbidity and mortality due to viral infections. It is associated with a reduced incidence of chronic GVHD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Immunosuppressive microenvironment in neuroblastoma

    Directory of Open Access Journals (Sweden)

    Vito ePistoia

    2013-06-01

    Full Text Available According to the cancer immunoediting model, the interplay between tumor cells and the host immune system is crucial for the control of tumor growth. NB is a pediatric tumor that presents with metastatic disease at diagnosis in about 50% of the cases, the majority of which have poor prognosis. In this Review article, immune escape pathways adopted by human neuroblastoma (NB cells are reviewed. These include intrinsic defects of tumor cells such impaired expression of the HLA class I related antigen processing machinery and functional alterations of the tumor microenvironment induced by NB cell-derived immunosuppressive molecules as MICA and HLA-G. Finally, examples of therapeutic interventions targeting the tumor microenvironment are discussed to emphasize the concept that successful cancer treatment may be achieved using this strategy.

  10. Haploidentical bone marrow transplants for haematological malignancies using non-myeloablative conditioning therapy and post-transplant immunosuppression with cyclophosphamide: results from a single Australian centre.

    Science.gov (United States)

    Bilmon, I A; Kwan, J; Gottlieb, D; Kerridge, I; McGurgan, M; Huang, G; George, B; Hertzberg, M; Bradstock, K F

    2013-02-01

    To demonstrate safety and efficacy of haploidentical bone marrow transplantation with non-myeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma. Human leukocyte antigen haploidentical bone marrow transplantation is a treatment option in patients with haematological malignancies who have no available human leukocyte antigen-matched donor but is limited by conditioning regimen toxicity, graft failure, relapse and graft-versus-host disease (GvHD). Twelve patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype-matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine and low-dose total body irradiation. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome. All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of nine assessable patients had complete donor chimerism. Four patients had grades II-III GvHD, and none had grade IV GvHD. Four patients developed limited stage chronic GvHD. Five patients with acute myeloid leukaemia relapsed. Two patients died of nonrelapse causes, both from other malignancies, and five patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163). This regimen is feasible and well tolerated in older patients with high-risk leukaemia or lymphoma, with minimal short-term toxicity and low rates of GvHD. The proportion of disease-free survivors indicates a graft-versus-malignancy effect is present in survivors. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  11. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Garred, Peter

    2013-01-01

    A markedly increased risk of cervical cancer is known in women immunosuppressed due to AIDS or therapy following organ transplantation. The aim of this review is to determine the association between other conditions affecting the immune system and the risk of cervical cancer. Patients with end......-stage renal disease seem to be at an increased risk of cervical cancer. A higher risk of cervical precancerous lesions was found in patients with some autoimmune diseases; particularly if treated with immunosuppressants. Among behavioral factors weakening the immune system, smoking appeared to strongly...... increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent...

  12. Review papers immunosuppressive treatment

    Directory of Open Access Journals (Sweden)

    Anna Kryś

    2014-03-01

    Full Text Available Sebaceous carcinoma (sebaceous gland carcinoma – SC is a very aggressive malignant skin tumor that arises from the epithelium of sebaceous glands. Sun exposure and long-term immunosuppression, mainly in organ transplant recipients, are the most common risk factors. The tumor was first well described by Allaire in 1891. Sebaceous carcinoma is rare and accounts for less than 1% of all cutaneous malignancies and from 1% to 5.5% of all eyelid malignancies. The most common localization is the eyelids, where it derives from the Meibomian and Zeiss glands. Most cases occur in woman between 60 and 80 years of age, but the tumor can be seen at any age, even in childhood. It appears mostly as a small, slowly growing, painless and firm mass, sometimes as a small yellowish plaque or ulceration. SC has a tendency for local recurrence and distant metastases. The local recurrence rate ranges from 9 to 36% and tends to appear within the first 5 years from diagnosis. The most effective method of treatment is surgical excision (Mohs’ microsurgical excision if it is possible. The rate of metastases is about 14-25%. The sites of metastases are usually lymph nodes, liver, lungs, bones, and brain. The mortality rate is about 22% but it increases to 50% at 5 years in patients with metastatic disease.

  13. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K

    2000-01-01

    Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV...... seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-alpha in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART....

  14. Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

    Science.gov (United States)

    Zent, Clive S.; Taylor, Ronald P.; Lindorfer, Margaret A.; Beum, Paul V.; LaPlant, Betsy; Wu, Wenting; Call, Timothy G.; Bowen, Deborah A.; Conte, Michael J.; Frederick, Lori A.; Link, Brian K.; Blackwell, Sue E.; Veeramani, Suresh; Baig, Nisar A.; Viswanatha, David S.; Weiner, George J.; Witzig, Thomas E.

    2014-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a phase II trial testing the efficacy and tolerability of a short duration regimen combining pentostatin, alemtuzumab, and low dose high frequency rituximab (PAR) designed to decrease the risk of treatment associated infections and limit loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n=36) or previously untreated with 17p13 deletion (17p13-)(n=3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional and eight patients had purine analogue refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy with only five (13%) patients having treatment limiting toxicity, and no treatment related deaths. Twenty-two (56%) patients responded to treatment with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression free survival was 7.2 months, time to next treatment 9.1 months, and overall survival 34.1 months. The majority of deaths (82%) were caused by progressive disease including transformed diffuse large B cell lymphoma (n=6). Correlative studies showed that low dose rituximab activates complement and NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR is a tolerable and effective therapy for CLL and that low dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  15. Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

    Science.gov (United States)

    Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

    2017-01-01

    This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67 + ) CD8 + T cells was increased at week 4, with further increase in both the CD4 + and CD8 + subsets (p cells increased at week 4 as the frequency of effector memory cells increased in the CD8 + subset (p cells decreased in both the CD8 + and CD4 + subsets (p regulatory T cells was reduced (p T cells decreased, and effector memory T cells increased (p T cells increased at 30-week follow-up (p T cells, including increased proliferative activity and cytotoxic potential.

  16. Vaccinations in children on immunosuppressive medications for renal disease.

    Science.gov (United States)

    Banerjee, Sushmita; Dissanayake, Pathum Vindana; Abeyagunawardena, Asiri Samantha

    2016-09-01

    Renal diseases are often treated with immunosuppressive medications, placing patients at risk of infections, some of which are vaccine-preventable. However, in such patients vaccinations may be delayed or disregarded due to complications of the underlying disease process and challenges in its management. The decision to administer vaccines to immunosuppressed children is a risk-benefit balance as such children may have a qualitatively diminished immunological response or develop diseases caused by the vaccine pathogen. Vaccination may cause a flare-up of disease activity or provocation of graft rejection in renal transplant recipients. Moreover, it cannot be assumed that a given antibody level provides the same protection in immunosupressed children as in healthy ones. We have evaluated the safety and efficacy of licensed vaccines in children on immunosuppressive therapy and in renal transplant recipients. The limited evidence available suggests that vaccines are most effective if given early, ideally before the requirement for immunosuppressive therapy, which may require administration of accelerated vaccine courses. Once treatment with immunosuppressive drugs is started, inactivated vaccines are usually considered to be safe when the disease is quiescent, but supplemental doses may be required. In the majority of cases, live vaccines are to be avoided. All vaccines are generally contraindicated within 3-6 months of a renal transplant.

  17. Influenza and Pneumococcal Vaccination Uptake in Patients with Rheumatoid Arthritis Treated with Immunosuppressive Therapy in the UK: A Retrospective Cohort Study Using Data from the Clinical Practice Research Datalink

    Science.gov (United States)

    Winthrop, Kevin L.; Pye, Stephen R.; Brown, Benjamin; Dixon, William G.

    2016-01-01

    Introduction Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK. The aims of this study were to describe the uptake of influenza and pneumococcal vaccinations in patients with RA in the UK, to compare the characteristics of those vaccinated to those not vaccinated and to compare vaccination rates across regions of the UK. Methods A retrospective cohort study of adults diagnosed with incident RA and treated with non-biologic immunosuppressive therapy, using data from a large primary care database. For the influenza vaccination, patients were considered unvaccinated on 1st September each year and upon vaccination their status changed to vaccinated. For pneumococcal vaccination, patients were considered vaccinated after their first vaccination until the end of follow-up. Patients were stratified by age 65 at the start of follow-up, given differences in vaccination guidelines for the general population. Results Overall (N = 15,724), 80% patients received at least one influenza vaccination, and 50% patients received a pneumococcal vaccination, during follow-up (mean 5.3 years). Of those aged below 65 years (N = 9,969), 73% patients had received at least one influenza vaccination, and 43% patients received at least one pneumococcal vaccination. Of those aged over 65 years (N = 5,755), 91% patients received at least one influenza vaccination, and 61% patients had received at least one pneumococcal vaccination. Those vaccinated were older, had more comorbidity and visited the GP more often. Regional differences in vaccination rates were seen with the highest rates in Northern Ireland, and the lowest rates in London. Conclusions One in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over five years of follow-up. There remains significant scope to improve

  18. Incidence and management of leukopenia/neutropenia in 233 kidney transplant patients following single dose alemtuzumab induction.

    Science.gov (United States)

    Smith, A; Couvillion, R; Zhang, R; Killackey, M; Buell, J; Lee, B; Saggi, B H; Paramesh, A S

    2014-12-01

    The purpose of this study was to determine the incidence and management strategies for post-transplant leukopenia/neutropenia in kidney recipients receiving alemtuzumab induction during the first year following transplantation. We prospectively identified 233 adult patients who underwent kidney transplantation with alemtuzumab induction at a single institution. The incidence and severity of leukopenia (white blood cell count [WBC] ≤2500/mm(3)) and neutropenia (absolute neutrophil count [ANC] ≤500/mm(3)) were evaluated at 1, 3, 6, and 12 months post-transplantation. We determined any association with cytomegalovirus (CMV) infection, graft rejection, and infections requiring hospitalization. We also reviewed interventions performed, including medication adjustments, treatment with granulocyte stimulating factor, and hospitalization. The combined incidence of either leukopenia or neutropenia was 47.5% (n = 114/233) with an average WBC nadir of 1700 ± 50/mm(3) at 131.0 ± 8.5 days and an average ANC nadir of 1500 ± 100/mm(3) at 130.4 ± 9.6 days. No significant difference in graft rejection, CMV infection, or infections requiring hospitalization was found in the leukopenia/neutropenia group vs the normal WBC group (P = .3). The most common intervention performed for leukopenia/neutropenia group was prophylactic medication adjustment. Six patients (5.2%) required a change in >1 medication. The majority of these patients also required granulocyte stimulating factor (61.5%; 32/52), with an average of 2.5 doses given. A total of 25 patients (21.9%) required hospitalization due to leukopenia/neutropenia with an average length of stay of 6 days. Kidney transplant patients receiving alemtuzumab induction required significant interventions due to leukopenia/neutropenia in the first year post-transplantation. These results suggest the need for additional studies aimed at defining the optimum management strategies of leukopenia/neutropenia in this population

  19. Immunosuppressive Therapy-Related Kaposi Sarcoma

    Science.gov (United States)

    ... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

  20. Immunosuppressive medication adherence in kidney transplant patients.

    Science.gov (United States)

    Lalić, Jelena; Veličković-Radovanović, Radmila; Mitić, Branka; Paunović, Goran; Cvetković, Tatjana

    2014-01-01

    To assess the degree of immunosuppressive medication adherence in kidney transplant patients (KTPs) and to determine if there is a difference in the rate of adherence to tacrolimus (Tac), cyclosporine (CsA) and sirolimus (Sir). From a total of 63 KTPs treated at the Clinic of Nephrology, Clinical Centre Niš, Serbia, 60 participated in the study by responding to questionnaires. They were divided into the adherence group (n = 43) and the nonadherence group (n = 17) according to their degree of adherence which was measured using a validated survey form, the simplified medication adherence questionnaire. The KTP adherence to the different immunosuppressive regimens (Tac, CsA and Sir) was compared. Statistical analysis was performed using the Student t test. Adherence was observed in 43 (71.7%) patients, and only 17 (28.3%) did not follow the prescribed therapy. The estimated glomerular filtration rate was significantly lower in the nonadherence group (38.52 ± 18.22 ml/min) than in the adherence group (52.43 ± 16.91 ml/min, p adherers and the nonadherers (6.30 ± 2.06 vs. 5.0 ± 1.52 ng/ml, p adherence. Nonadherence was associated with worse graft function and a lower Tac level. Knowledge about the degree of adherence could help the early identification of nonadherent patients and the development of strategies to improve this. © 2014 S. Karger AG, Basel

  1. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Holland, G.N.; O' Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-06-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

  2. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    International Nuclear Information System (INIS)

    Holland, G.N.; O'Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-01-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease

  3. Noninvasive ventilation in immunosuppressed patients.

    Science.gov (United States)

    Namendys-Silva, Silvio A; Hernández-Garay, Marisol; Herrera-Gómez, Angel

    2010-03-01

    In immunosuppressed patients (ISP) with acute respiratory failure (ARF), invasive mechanical ventilation (IMV) is associated with high mortality rate. Noninvasive ventilation (NIV) is a type of mechanical ventilation that does not require an artificial airway. It has seen increasing use in critically ill patients to avoid endotracheal intubation. Acute respiratory failure due to pulmonary infections is an important cause of illness in ISP and their treatment. Immunosuppressive treatments have showed an increase not only in the survival but also in the susceptibility to infection. Several authors have underlined the worst prognosis for neutropenic patients with ARF requiring endotracheal intubation and IMV. The NIV seems to be an interesting alternative in ISP because of the lower risk of complications; it prevents endotracheal intubation and its associated complications with survival benefits in this population.

  4. Immunosuppression: Have We Learnt Anything?

    Science.gov (United States)

    Hachem, Ramsey R

    2018-04-01

    Outcomes after lung transplantation remain disappointing because there is a high incidence of chronic lung allograft dysfunction (CLAD), which typically follows a progressive clinical course and often results in allograft failure and death. Chronic rejection is considered the predominant cause of CLAD. Thus, optimal immunosuppression has been viewed as having the potential to prevent CLAD and improve survival after lung transplantation. Numerous clinical trials have been conducted investigating the efficacy and safety of various immunosuppressive agents. Many studies have been small and single-center clinical trials but some have been international and multicenter trials enrolling more than 300 patients. This review focuses on clinical trials of immunosuppression conducted in lung transplantation and points out strengths and limitations of the various studies. Ultimately, the findings of these clinical trials explain the current state of practice in lung transplantation and identify gaps in knowledge that require additional study. Finally, there is an ongoing need for carefully designed and conducted clinical trials to improve clinical practice and outcomes after lung transplantation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Heart transplant survival in non-human primates : T cell-directed immunosuppressive therapy and regulatory T cells for promotion of heart transplant survival in non-human primates

    NARCIS (Netherlands)

    E.M. Dons (Eefje)

    2013-01-01

    textabstractHeart transplantation significantly enhances the life expectancy of adult patients suffering heart failure, and infants born with malformations of their heart. However, there are many hurdles such as rejection of the transplanted organ, or side effects of the immunosuppressive drugs,

  6. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth

    Directory of Open Access Journals (Sweden)

    Han Zhipeng

    2012-03-01

    Full Text Available Abstract Mesenchymal stem cells (MSCs have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance.

  7. Rationale, design, and methods of a non-interventional study to establish safety, effectiveness, quality of life, cognition, health-related and work capacity data on Alemtuzumab in multiple sclerosis patients in Germany (TREAT-MS)

    OpenAIRE

    Ziemssen, Tjalf; Engelmann, Ulrich; Jahn, Sigbert; Leptich, Alexandra; Kern, Raimar; Hassoun, Lina; Thomas, Katja

    2016-01-01

    Background Alemtuzumab, a humanized monoclonal antibody directed against the cell surface glycoprotein CD52, is licensed in Europe since October 2013 as treatment for adult patients with active relapsing-remitting multiple sclerosis (RRMS). In three randomized, rater-blinded active comparator clinical trials studies, alemtuzumab administered in two annual courses, had superior efficacy as compared to subcutaneous interferon beta-1a, and durable efficacy over 5?years in an extension study with...

  8. Clinical pharmacogenetics of immunosuppressive drugs in organ transplantation.

    Science.gov (United States)

    Szekeres, Thomas; Haushofer, Alexander

    2005-03-01

    Organ transplantation has become an important additional option for patients with organ failure. Immunosuppressive drugs showing a very narrow therapeutic window have to be administered. Different transporters and metabolic pathways are responsible for absorption and metabolism of these drugs; for instance, the P-glycoprotein (P-gp) pump regulates the absorption of a drug, and its metabolism is catalyzed by cytochrome P450s (CYPs). As the phenotypes of P-gp or the CYPs are predetermined by their genotypes, genetic testing prior to drug therapy may help to predict the drug doses required. This review describes polymorphisms of the genes coding for P-gp and CYPs, and focuses on the compounds cyclosporin and tacrolimus. It is hoped that this information might help to judge the value of pharmacogenetic testing prior to immunosuppressive therapy in solid organ transplantation.

  9. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient].

    Science.gov (United States)

    Riveiro-Barciela, Mar; Buti, María

    2015-01-01

    Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  10. South American Heart Transplantation Registry of patients receiving everolimus in their immunosuppressive regimens.

    Science.gov (United States)

    Bortman, G V; Ceruti, B; Ahualli, L; Colque, R; Amuchástegui, M; Sgrosso, J L; Muñoz, J; Vulcano, N; Burgos, C; Diez, F; Rodriguez, M C; Perrone, S V

    2010-01-01

    The increasing number of heart transplant recipients receiving immunosuppression with mammalian target of rapamycin inhibitors prompted the implementation of a South American Transplant Physicians Group to register these patients in a database. Everolimus (EVL) is a signal proliferation inhibition that reduces graft vascular disease when used de novo. Recently, its administration has expanded to subjects with resistant rejection or with side effects due to other immunosuppressive drugs (calcineurin inhibitors and/or steroids), allowing for better regulation of the immunosuppressive regimen. Herein we have shown the data collected from patients receiving EVL in ten South American Heart Transplant Centers. We have concluded that the administration of EVL is a useful adjunctive therapy that allows the reduction or suspension of other immunosuppressive drugs that caused unwanted side effects, without a loss of immunosuppressive efficacy, with manageable side effects, and constituting a valuable therapeutic option.

  11. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

    Science.gov (United States)

    Guenova, Emmanuella; Lichte, Verena; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

    2009-08-01

    Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.

  12. Awareness of memory impairment increases the adherence to immunosuppressants in kidney transplant recipients.

    Science.gov (United States)

    Cheng, C-Y; Lin, B Y-J; Chang, K-H; Shu, K-H; Wu, M-J

    2012-04-01

    Nonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients. All data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients. In summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Immunosuppressant prescription pattern and trend in kidney transplantation: A multicenter study in Korea.

    Directory of Open Access Journals (Sweden)

    Ji-Yeun Chang

    Full Text Available The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear.We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy.Most patients (n = 621, 97.6% received induction therapy often comprising basiliximab (n = 542, 85.2%. The triple therapy including calcineurin inhibitor, mycophenolic acid, and steroids was the major initial maintenance immunosuppression (n = 518, 81.4%, but its proportion decreased by 14% (81.4% to 67.5% after 1 year. Almost 40% of patients changed immunosuppressive regimen during the 1-year follow-up, most often at an early period (60.2% within the first 4 months. The primary reason for the change was gastrointestinal discomfort (n = 113, 29.8%, followed by infection (112, 29.6%. The most common changing pattern was mycophenolic acid withdrawal (n = 155, 39.1%.The initial immunosuppressive regimen is prone to change within the first year of kidney transplantation. Further studies are needed to evaluate the benefits and risks in patients who changed immunosuppressants.

  14. Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL

    DEFF Research Database (Denmark)

    Geisler, Christian H; van T' Veer, Mars B; Jurlander, Jesper

    2014-01-01

    heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133......). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035...

  15. Immunosuppressive sesquiterpenes from Buddleja daviddi.

    Science.gov (United States)

    Zhang, Wen; Yao, Zhi; Zhang, Yan Wen; Zhang, Xing Xiang; Takaishi, Yoshihisa; Duan, Hong Quan

    2010-11-01

    Six new sesquiterpenes, 2,6(12),10-humulatrien-7β-ol-1-one (1), 2 α-acetoxy-5α-methoxy-enantio-caryophylla-8(15)-en-3-one (2), 2α-acetoxy-5α-hydroxy-enantio-caryophylla-8(15)-en-3-one (3), 2α-acetoxy-4β,5α-hydroxy-enantio-caryophylla-8(15)-en-3-one ( 4), 2α-acetoxy-4β,5β-hydroxy-enantio-caryophylla-8(15)-en-3-one (5), 2β-acetoxy-4-caryophyllen-8β-ol-3-one (6), and nineteen known compounds were isolated from the ethanol extract of Buddleja daviddi. The structures were elucidated by spectroscopic methods. Compounds 8-11, 14, 16, 17, and 20 showed significant immunosuppressive activities, and 8-11 and 14 were cytotoxic on HeLa and L929 cell lines. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis.

    Science.gov (United States)

    Cui, Xin; Morales, Renee-Tyler Tan; Qian, Weiyi; Wang, Haoyu; Gagner, Jean-Pierre; Dolgalev, Igor; Placantonakis, Dimitris; Zagzag, David; Cimmino, Luisa; Snuderl, Matija; Lam, Raymond H W; Chen, Weiqiang

    2018-04-01

    altered ECM. Hence, we provide an interactive and controllable GBM tumor microenvironment and highlight the importance of macrophage-associated immunosuppression in GBM angiogenesis, paving a new direction of screening novel anti-angiogenic therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Immunomodulator, immunosuppression of radiation and immune reconstruction

    International Nuclear Information System (INIS)

    Mao Jianping; Fang Jing; Zhou Ying; Cui Yufang; Jiang Zhujun; Du Li; Ma Qiong

    2010-01-01

    There is a refined and complicated regulatory network between immune cells, and between immune cells and secretory factors. The immune system is kept in a homeostasis and equilibrium by positive activation and negative inhibition. In recent years, the mechanisms of immunosuppression in depth for successful allograft transplantation were studied, and many immunosuppressants and immunosuppressive drugs have been developed for clinical use. Most of them are targeting T cell receptors and three kinds of singnal pathways. The receptors of the immunosuppression were either found highly expressed in immune cells after irradiation. To relieve the suppression by regulating the receptors could help the immune reconstruction out of radiation damage. Many new immunoenhancers have been discovered to improve the immune system function for radiation by Toll-like receptors. The search for new immunoenhancers and agents for relieving immunosuppression is of great importance to immune construction for radiation sickness. (authors)

  18. Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Galvao, M.M.; Ianhez, L.E.; Sabbaga, E. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

    1982-02-01

    The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic /sup 131/I as a pre-transplantation immunosuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunosuppressive therapy. Significant differences were observed between the two groups regarding such factors as incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunosuppressive action, its administration being advised for receptors of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel.

  19. Experimental paracoccidioidomycosis in immunosuppressed mice

    Energy Technology Data Exchange (ETDEWEB)

    Kerr, I.B.; Costa, S.C.G.; Alencar, A. (Instituto de Radioterapia Osvaldo Cruz, Sao Paulo (Brazil))

    1982-09-01

    Mice were immunosuppressed by means of whole-body irradiation or cyclophosphamide, in order to investigate the influence on the initial phase of infection induced by a strain of the fungus, Paracoccidioides brasiliensis, in the yeast phase and inoculated intraperitoneally. A group of mice was irradiated with 600 rad (cobalt ..gamma..-irradiation) 24 h before infection. Two groups were treated with cyclophosphamide (200 mg/kg intravenously), one two days before, and the other, one day after infection. A control group received the fungus, but no radiation of cyclophosphamide. All animals developed lesions at the site of inoculation. Metastatic lesions were observed in 100% of the animals in the irradiated group, 67% in each of the cyclophosphamide-treated groups and 33% in the control group. These lesions were found both in the liver and lungs, being more numerous in the irradiated group, followed by the cyclophosphamide-treated group in which the drug was given after the infection; they were slight in both viscera in the other cyclophosphamide-treated group and also slight in the liver and absent in the lungs of the controls.

  20. Experimental paracoccidioidomycosis in immunosuppressed mice

    International Nuclear Information System (INIS)

    Kerr, I.B.; Costa, S.C.G.; Alencar, A.

    1982-01-01

    Mice were immunosuppressed by means of whole-body irradiation or cyclophosphamide, in order to investigate the influence on the initial phase of infection induced by a strain of the fungus, Paracoccidioides brasiliensis, in the yeast phase and inoculated intraperitoneally. A group of mice was irradiated with 600 rad (cobalt γ-irradiation) 24 h before infection. Two groups were treated with cyclophosphamide (200 mg/kg intravenously), one two days before, and the other, one day after infection. A control group received the fungus, but no radiation of cyclophosphamide. All animals developed lesions at the site of inoculation. Metastatic lesions were observed in 100% of the animals in the irradiated group, 67% in each of the cyclophosphamide-treated groups and 33% in the control group. These lesions were found both in the liver and lungs, being more numerous in the irradiated group, followed by the cyclophosphamide-treated group in which the drug was given after the infection; they were slight in both viscera in the other cyclophosphamide-treated group and also slight in the liver and absent in the lungs of the controls. (Auth.)

  1. A rationale for age-adapted immunosuppression in organ transplantation

    Science.gov (United States)

    Krenzien, Felix; ElKhal, Abdallah; Quante, Markus; Biefer, Hector Rodriguez Cetina; Hirofumi, Uehara; Gabardi, Steven; Tullius, Stefan G.

    2015-01-01

    Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older >50 years and organs from elderly donors are more frequently utilized. Nevertheless, the benefit of transplantation in older patients is well recognized whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants. Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients while the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus following transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors and mTOR inhibitors. This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly. PMID:26244716

  2. Pneumonia in immunosuppressed patients; Pneumonien bei immunsupprimierten Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Solyanik, O.; Gaass, T.; Hellbach, K. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Dinkel, J. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Comprehensive Pneumology Center Munich (CPC-M), Muenchen (Germany)

    2017-01-15

    Pulmonary infections are a common complication in immunosuppressed patients with a frequently fatal prognosis despite modern prophylactic therapy. An early and correct diagnosis is important for initiation of the appropriate therapy. Chest radiography is the preferred initial imaging examination but is not accurate enough for the detection of pulmonary infections in immunosuppressed patients. Pneumonia is caused by a broad spectrum of pathogens in immunocompromised patients. In addition to imaging, the clinical history and epidemiology also play an important role in the diagnostics. Using epidemiological and anamnestic information, computed tomography (CT) shows a significantly better sensitivity and specificity particularly for the diagnosis of atypical forms of pneumonia. Due to the exact imaging of the different infiltration patterns CT provides an increased sensitivity with respect to the etiological classification of pulmonary infections. This article reviews in particular the radiological findings of commonly occurring pulmonary infections in immunosuppressed patients. (orig.) [German] Pneumonien bei immunsupprimierten Patienten sind haeufige Komplikationen, die trotzt moderner Prophylaxe toedlich verlaufen koennen. Eine korrekte Diagnose ist daher von entscheidender Bedeutung, um die richtige Therapie einleiten zu koennen. Die Roentgenthoraxaufnahme ist selten spezifisch genug fuer die genaue Einordnung atypischer Pneumonien in Folge einer Immunsuppression. Pneumonien unter Immunsuppression werden durch ein sehr breites Erregerspektrum verursacht. Eine wichtige Rolle bei der Diagnosefindung spielen neben der Bildgebung auch die klinische Anamnese und Epidemiologie. Mithilfe der klinischen Anamnese und Epidemiologie bietet die Computertomographie (CT) bei immunsupprimierten Patienten zum einen eine erhoehte Sensitivitaet bei der Detektion insbesondere atypischer Pneumonien. Zum anderen weist die CT durch die exakte Abbildung unterschiedlicher Infiltratmuster

  3. The impact of immunosuppression on erythema migrans. A retrospective study of clinical presentation, response to treatment and production of Borrelia antibodies in 33 patients.

    Science.gov (United States)

    Fürst, B; Glatz, M; Kerl, H; Müllegger, R R

    2006-07-01

    Little is known about the potential influence of immunosuppression on erythema migrans, the hallmark of early Lyme borreliosis. We performed a retrospective study to assess the impact of immunosuppression on erythema migrans in 33 patients with a malignant or autoimmune disease, chronic infection, or immunosuppressive therapy for organ transplantation. Only patients with active disease status and/or current immunosuppressive therapy were included. Pre-treatment clinical parameters, such as presentation of the skin lesion and presence of extracutaneous signs and symptoms, the disease course during a median follow-up of 9 months after therapy and serum anti-Borrelia burgdorferi antibodies before therapy and by the end of follow-up in the 33 immunosuppressed patients were statistically compared with 75 otherwise healthy patients with erythema migrans. The 75 control patients were matched for sex, age and antibiotic therapy. With the exception of the site of erythema migrans lesions, which were found more often on the trunk than on the legs in the immunosuppressed patients (vice versa in immunocompetent patients), we found no significant differences for all investigated parameters between the two groups. It appears that immunosuppression does not influence clinical presentation, response to therapy, or production of anti-B. burgdorferi antibodies of patients with erythema migrans. It is thus not necessary to treat immunosuppressed patients with erythema migrans differently from immunocompetent patients.

  4. Menopause in women with chronic immunosuppressive treatment ? how to help those patients

    OpenAIRE

    Cyganek, Anna; Pietrzak, Bronis?awa; Wielgo?, Miros?aw; Grzechoci?ska, Barbara

    2016-01-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General ...

  5. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Clinical Trial of FK 506 Immunosuppression in Adult Cardiac Transplantation

    Science.gov (United States)

    Armitage, John M.; Kormos, Robert L.; Morita, Shigeki; Fung, John; Marrone, Gary C.; Hardesty, Robert L.; Griffith, Bartley P.; Starzl, Thomas E.

    2010-01-01

    The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient. PMID:1379032

  7. Bacterial Meningitis in Patients using Immunosuppressive Medication: a Population-based Prospective Nationwide Study.

    Science.gov (United States)

    van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2017-06-01

    We studied occurrence, presentation, disease course, effect of adjunctive dexamethasone, and prognosis of bacterial meningitis in patients using immunosuppressive medication. Patients were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 1, 2006 through October 31, 2014. Eighty-seven of 1447 episodes (6 %) of bacterial meningitis occurred in patients using immunosuppressive medication, and consisted of corticosteroids in 82 %. Patients with bacterial meningitis using immunosuppressive medication were less likely to present with headache (P = 0.02) or neck stiffness (P = 0.005), as compared those not on immunosuppressive medication. In 46 % of episodes CSF leukocyte count was below 1000/mm 3 . CSF cultures revealed S. pneumoniae in 41 % and L. monocytogenes in 40 % of episodes. Outcome was unfavorable in 39 of 87 episodes (45 %) and death occurred in 22 of 87 episodes (25 %). Adjunctive dexamethasone was administered in 52 of 87 (60 %) episodes, and mortality tended to be lower in those on adjunctive dexamethasone therapy as compared to those without dexamethasone therapy (10 of 52 [19 %] vs 12 of 35 [34 %], P = 0.14). We conclude that bacterial meningitis in patients using immunosuppressive medication is likely to present with atypical clinical and laboratory features, and is often caused by atypical bacteria, mainly L. monocytogenes. Adjunctive dexamethasone is widely prescribed in these patients and was not associated with harm in this study.

  8. A comparison of traditional versus contemporary immunosuppressive regimens in pediatric heart recipients.

    Science.gov (United States)

    Marshall, Clement D; Richmond, Marc E; Singh, Rakesh K; Gilmore, Lisa; Beddows, Kim; Chen, Jonathan M; Addonizio, Linda J

    2013-07-01

    To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction). We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups. The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15). A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival. Copyright © 2013 Mosby, Inc. All rights reserved.

  9. Immunosuppressants in Oral Medicine: A Review

    Directory of Open Access Journals (Sweden)

    Aravinda Konidena

    2017-01-01

    Full Text Available Immunologically mediated mucocutaneous diseases constitute a large group of oral mucosal disorders that compromise the quality of life of patients due to their chronicity. The treatment of these disorders should not only be directed to bring relief from symptoms but also towards treating the underlying immune dysregulation, prevent recurrences, and preserve organ integrity and function. These disorders are largely treated by immunosuppressants. Challenge in treating these disorders lies in existing comorbidities, frequent relapses or short disease-free intervals, and long-term use of medication and their complications. This review focusses on newer immunosuppressants and their role in oral mucosal disorders.

  10. Cutaneous toxoplasmosis in an immunosuppressed dog

    Directory of Open Access Journals (Sweden)

    T.S. Oliveira

    2014-06-01

    Full Text Available A seven-year-old female spayed Schnauzer was presented with cutaneous ulcerated nodular lesions shortly after the beginning of an immunosuppressive treatment for immune-mediated hemolytic disease. Cytology was performed and a great number of neutrophils and banana-shaped organisms were observed. Biopsy showed a neutrophilic and histiocytic dermatitis and panniculitis with myriads of intralesional bradyzoites cysts and tachyzoites. PCR analysis was positive for Toxoplasma gondii and negative for Neospora caninum. Immunohistochemistry confirmed intralesional T. gondii antigens. This study reports a rare case of cutaneous toxoplasmosis in an immunosuppressed dog.

  11. Factors that determine self-reported immunosuppressant adherence in kidney transplant recipients: a correlational study.

    Science.gov (United States)

    Weng, Li-Chueh; Yang, Ya-Chen; Huang, Hsiu-Li; Chiang, Yang-Jen; Tsai, Yu-Hsia

    2017-01-01

    To determine the factors related to immunosuppressant therapy adherence in kidney transplant recipients in Taiwan. Adherence to immunosuppressant treatment is critical after kidney transplantation. Thus, the factors associated with self-reported medication adherence in kidney transplant recipients warrant investigation. The study used a cross-sectional and correlation design. A convenience sample of 145 kidney transplant recipients was included. Structured questionnaires were used to collect data during 2012-2013. Multivariate linear regression was used to examine the factors related to immunosuppressant therapy adherence. Over half of the participants were female (54·5%), mean age was 45·5 years, and mean year after transplant was 7·4. The mean score for medication adherence was 29·73 (possible score range 7-35). The results of the multivariate linear regression analysis showed that gender (male), low income with a high school or college education, years after transplantation and concerns about medication taking were negatively associated with adherence. Medication self-efficacy was positively associated with adherence. Therapy-related factors, partnerships with healthcare professionals and having private healthcare insurance did not significantly relate to immunosuppressant therapy adherence. Kidney transplant recipients demonstrated a high level of adherence. Strategies to enhance patients' self-efficacy and alleviate concerns about medication may promote medication adherence. Male patients, those with a lower income and those with a higher education level, should be a focus of efforts to maintain adherence to the medication regimen. © 2016 John Wiley & Sons Ltd.

  12. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

    NARCIS (Netherlands)

    Khanna, Reena; Bressler, Brian; Levesque, Barrett G.; Zou, Guangyong; Stitt, Larry W.; Greenberg, Gordon R.; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J.; Donner, Allan; Vandervoort, Margaret K.; Morris, Joan C.; Feagan, Brian G.; Anderson, Frank; Atkinson, Kenneth; Bacchus, Rahman; Berezny, Gary; Borthistle, Bruce; Buckley, Alan; Chiba, Naoki; Cockeram, Alan; Elkashab, Magdy; Fashir, Baroudi; Gray, James; Hemphill, Douglas; Hoare, Connie; Holland, Stephen; Hurowitz, Eric; Kaal, Nuri; Laflamme, Pierre; Borromee, Saint-Charles; Lau, Helena; McMullen, William; Memiche, Reshat; Menon, Krishna; Miller, D. Alexander; O'Hara, William; Oravec, Michael; Penner, Robert; Petrunia, Denis; Pluta, Henryk; Prabhu, Umesh; Prest, Marcia; Shaaban, Hani; Sheppard, Duane; Shulman, Scott

    2015-01-01

    Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of

  13. Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers

    Directory of Open Access Journals (Sweden)

    Håkon Reikvam

    2018-01-01

    intermediate group including cGVHD patients with limited organ involvement. We conclude that allotransplant recipients with cGVHD have an altered metabolic profile caused both by the disease and its immunosuppressive treatment.

  14. Merkel Cell Carcinoma in Immunosuppressed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Janice E. [Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States); Brewer, Jerry D., E-mail: brewer.jerry@mayo.edu [Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States)

    2014-06-27

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients.

  15. Immune tolerance and immunosuppression in solid organ ...

    African Journals Online (AJOL)

    Organ transplantation is the treatment of choice for patients with end-stage organ failure. Most of them will require lifelong immunosuppression to prevent both acute and chronic rejection. T-cell recognition of the allograft major histocompatibility complex antigens is the central event initiating cellular rejection of the allograft, ...

  16. Merkel Cell Carcinoma in Immunosuppressed Patients

    International Nuclear Information System (INIS)

    Ma, Janice E.; Brewer, Jerry D.

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients

  17. Lymphocyte adenylate cyclase activity in immunosuppressed patients

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.

    1989-01-01

    In order to determine whether alterations of adenylate cyclase are involved in the immunosuppressive effect of glucocorticoid/cyclosporin treatment we measured basal, prostaglandin E1-, and forskolin-stimulated cAMP production in lymphocyte membranes from kidney transplant patients undergoing

  18. Putative Bronchopulmonary Flagellated Protozoa in Immunosuppressed Patients

    Directory of Open Access Journals (Sweden)

    Ali Ahmet Kilimcioglu

    2014-01-01

    Full Text Available Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be “flagellated protozoa” have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2% of 110 cases. Metronidazole (500 mg b.i.d. for 30 days was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  19. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    Science.gov (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  20. Renal transplant patients’ preference for the supply and delivery of immunosuppressants in Wales: a discrete choice experiment

    OpenAIRE

    Hagemi, Anke; Plumpton, Catrin; Hughes, Dyfrig A.

    2017-01-01

    Background Prescribing policy recommendations aimed at moving immunosuppressant prescribing for renal transplant patients from primary to secondary care may result in benefits of increased safety and reduced cost. However, there is little evidence of patients’ preferences for receiving their immunosuppressant therapy from hospitals compared to community dispensing. The aim of this study was to elicit patient preferences for different service configurations focusing in particular on home deliv...

  1. Análise da eficácia do laser de baixa potência no tratamento da dor tendínea em ratos imunossuprimidos Analysis of low-level laser therapy efficacy on tendon pain treatment in immunosuppressed rats

    Directory of Open Access Journals (Sweden)

    Fernanda de Oliveira Busarello

    2011-12-01

    Full Text Available O comprometimento do sistema imune, que pode ser apresentado por indivíduos com doenças crônicas, leva à baixa resposta imunológica. Um dos tratamentos utilizados para lesões agudas em tendões é o laser de baixa potência, contudo há uma lacuna em relação ao seu uso em imunodepressão. O objetivo do presente estudo foi analisar se o laser de baixa potência é eficaz para o tratamento da dor em ratos imunodeprimidos submetidos a trauma tendíneo. Foram utilizados 23 ratos, machos, da linhagem Wistar, divididos aleatoriamente em três grupos: grupo controle, placebo e laser. Os animais foram imunodeprimidos (por administração de Ciclosporina A e submetidos à lesão no tendão calcâneo direito, com impacto de cerca de 0,40 J. Para o tratamento, utilizou-se laser de baixa potência, 670 nm, 30 mW e dose de 2 J/cm², durante 3 dias. A avaliação da dor foi realizada pelo teste de incapacidade funcional e por filamento de Von Frey digital. Os resultados apresentaram valores significativos para o grupo laser, com diminuição de dor funcional e da dor à pressão na superfície plantar e no local lesionado (tendão calcâneo direito. Portanto, concluiu-se que o laser de baixa potência é eficaz para reduzir a dor em ratos imunodeprimidos submetidos a trauma tendíneo.The commitment of immune system, which may be presented by individuals with chronic diseases, leading to a low immune response. One of the treatments used for acute injuries in tendons is the low-power laser, however there is a gap in relation to its use in immunosuppression. The objective of this study was to analyze if low-level laser therapy is effective for the treatment of pain in immunosuppressed rats subjected to trauma tendon. We used 23 male rats of Wistar strain, divided randomly in three groups: control group, placebo and laser. The animals were immunosuppressed (by administration of Cyclosporin A and underwent right Achilles tendon injury, with impact of about

  2. Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

    Science.gov (United States)

    Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

    2016-03-01

    Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant. © The Author(s) 2015.

  3. Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.

    Science.gov (United States)

    Mohamedbhai, Sajir G; Edwards, Noha; Morris, Emma C; Mackinnon, Stephen; Thomson, Kirsty J; Peggs, Karl S

    2012-02-01

    The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning. © 2011 Blackwell Publishing Ltd.

  4. Immunosuppressant therapy and bone loss in ligature-induced periodontitis: a study in rats Terapia imunossupressora e perda óssea em periodontite induzida por ligaduras: um estudo em ratos

    Directory of Open Access Journals (Sweden)

    Patricia Furtado Gonçalves

    2003-03-01

    Full Text Available Immunosuppressive agents have been recognized as a factor affecting the soft tissues of the periodontium. However, little is known about their effect on periodontitis progression. The aim of the present study was to investigate the influence of cyclosporin A (CsA administration, associated or not with nifedipine, on the bone loss resulting from a ligature-induced periodontitis in rats. Twenty-four adult male Wistar rats were used. After anesthesia, the mandibular first molar was randomly assigned to receive the cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments: Group A - saline solution; Group B - CsA (10 mg/kg; Group C - nifedipine (50 mg/kg; Group D - CsA (10 mg/kg plus nifedipine (50 mg/kg. Forty-five days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Intergroup analysis did not reveal significant differences regarding the bone loss volume in the ligated teeth between the experimental treatments (0.46 ± 0.11, 0.63 ± 0.32, 0.53 ± 0.14, 0.50 ± 0.18, for groups A, B, C and D, respectively - p > 0.05. However, intragroup analysis showed a greater bone loss volume in the ligated teeth than in the unligated ones (p O uso de agentes imunossupressores tem sido reconhecido como um fator que afeta os tecidos moles do periodonto. Entretanto, pouco se sabe sobre o seu efeito na progressão da periodontite. O objetivo do presente estudo foi investigar a influência da ciclosporina (CsA, associada ou não à nifedipina, na perda óssea resultante da periodontite induzida por ligaduras em ratos. Vinte e quatro ratos Wistar machos, adultos, foram incluídos no estudo. Após anestesia, foram colocadas ligaduras de fio de algodão ao redor do primeiro molar inferior direito ou esquerdo, aleatoriamente escolhido. O dente contralateral foi deixado sem ligadura. Os animais foram aleatoriamente

  5. Adverse reactions of immunosuppressive drugs in Iranian adult kidney transplant recipients.

    Science.gov (United States)

    Namazi, Soha; Sagheb, Mohammad Mahdi; Karimzadeh, Iman

    2012-06-01

    To evaluate the pattern of immunosuppressive drug adverse reactions in adult kidney transplant recipients in Iran. Adult kidney transplant outpatients under immunosuppressive therapy were recruited into the study. All adverse drug reactions to immunosuppressants and their relevant clinical and paraclinical characteristics were recorded. Causality assessment was performed by the Naranjo algorithm. The seriousness of adverse drug reactions was determined by the World Health Organization definition. The Schumock and Thornton questionnaire was used to assess the preventability of adverse drug reactions. Statistical analyses were performed. A total of 1100 adverse drug reactions were detected from 120 kidney transplant recipients. Increased appetite (9.09%) was the adverse reaction reported most frequently. Causality assessment revealed that 1019 adverse drug reactions (92.64%) were possible. Forty adverse drug reactions (3.64%) were identified as serious. Six hundred seventy-one adverse drug reactions (61%) were preventable. Posttransplant duration was significantly correlated with the number of adverse drug reactions (R=0.19; P = .035). All renal allograft recipients experienced at least 1 immunosuppressant-related adverse reaction. Prolongation of immunosuppressive treatment resulted in an increase in adverse drug reactions.

  6. Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Natarajaswamy Kalleda

    2016-07-01

    Full Text Available Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.

  7. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    Science.gov (United States)

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  8. Immunosuppression in the elderly renal allograft recipient

    DEFF Research Database (Denmark)

    Montero, Nuria; Pérez-Sáez, María José; Pascual, Julio

    2016-01-01

    BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression...... strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus...... receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account...

  9. Alemtuzumab – nowy lek w terapii postaci rzutowej stwardnienia rozsianego. Pierwsza czy druga linia leczenia?

    Directory of Open Access Journals (Sweden)

    Jacek Zaborski

    2015-11-01

    Full Text Available Alemtuzumab jest humanizowanym przeciwciałem monoklonalnym skierowanym przeciwko glikoproteinie CD52, powodującym deplecję (eliminację krążących limfocytów T i B. Proces odtwarzania obu populacji limfocytów przebiega odmiennie, co prowadzi do zaburzeń w układzie odpornościowym. Zmiany te skutkują zmniejszeniem aktywności procesu chorobowego. Skuteczność alemtuzumabu została potwierdzona w trzech badaniach klinicznych: jednym fazy drugiej – CAMMS223 oraz dwóch fazy trzeciej – CARE-MS I i CARE-MS II. W badaniach tych wykazano skuteczność kliniczną podawanego dożylnie alemtuzumabu u chorych z postacią rzutową stwardnienia rozsianego. Komparatorem był podawany podskórnie interferon beta-1a. W CAMMS223 i CARE-MS I wykazano istotny wpływ alemtuzumabu na spadek wskaźnika rzutów w porównaniu z interferonem, a w CAMMS223 i CARE-MS II – wpływ na zwolnienie narastania niesprawności. Terapia z zastosowaniem alemtuzumabu nie była wolna od istotnych działań niepożądanych, które należały do trzech zasadniczych grup: działania niepożądane bezpośrednio związane z podawaniem leku, ciężkie infekcje oraz zaburzenia autoimmunologiczne (samoistna plamica małopłytkowa, zaburzenia funkcji tarczycy i nefropatia. Terapia alemtuzumabem może być zarówno skuteczna, jak i bezpieczna, jednakże pod warunkiem zachowania właściwego programu monitorowania działań niepożądanych.

  10. Immunosuppression associated with chronic inflammation in the tumor microenvironment

    Science.gov (United States)

    Wang, Dingzhi; DuBois, Raymond N.

    2015-01-01

    Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID:26354776

  11. Varicella-zoster virus immunity in dermatological patients on systemic immunosuppressant treatment.

    LENUS (Irish Health Repository)

    Hackett, C B

    2012-02-01

    BACKGROUND: Primary varicella infection is caused by varicella-zoster virus (VZV). It is a common childhood infection, which is usually benign but can occasionally cause morbidity and mortality. In immunosuppressed adults, atypical presentation and disseminated disease can occur with significant morbidity and mortality. A VZV vaccine is available. OBJECTIVES: This study was designed to measure the prevalence of immunity to VZV and to determine the predictive value of a self-reported history of varicella infection in a population of dermatological patients receiving systemic immunosuppressant therapy. We sought to assess the need for routine serological testing for varicella-zoster immunity in this cohort. METHODS: Serological testing for VZV immunity was done on 228 patients receiving systemic immunosuppressive treatment for a dermatological condition. Information regarding a history of previous primary VZV infection was obtained from each patient. RESULTS: Two hundred and twenty-eight patients had VZV serology performed. The mean age of the patients was 49.6 years. The prevalence of VZV seropositivity in this cohort was 98.7%. One hundred and two patients (44.7%) reported having a definite history of primary VZV. The sensitivity of a self-reported history of VZV infection was 45.3% with a specificity of 100%. The positive and negative predictive values of a self-reported history of VZV for serologically confirmed immunity were 100% and 2.3%, respectively. CONCLUSIONS: The prevalence of VZV IgG antibodies in our cohort of Irish dermatology patients receiving immunosuppressive therapy is 98.7%. A recalled history of varicella infection is a good predictor of serological immunity. This study has shown that there are VZV-susceptible individuals within our cohort. These patients did not have a clear history of previous infection. We recommend serological testing of patients without a clear history of infection prior to the commencement of immunosuppressive therapy and

  12. Enteric glial cells have specific immunosuppressive properties.

    Science.gov (United States)

    Kermarrec, Laetitia; Durand, Tony; Neunlist, Michel; Naveilhan, Philippe; Neveu, Isabelle

    2016-06-15

    Enteric glial cells (EGC) have trophic and neuroregulatory functions in the enteric nervous system, but whether they exert a direct effect on immune cells is unknown. Here, we used co-cultures to show that human EGC can inhibit the proliferation of activated T lymphocytes. Interestingly, EGC from Crohn's patients were effective at one EGC for two T cells whereas EGC from control patients required a ratio of 1:1. These data suggest that EGC contribute to local immune homeostasis in the gastrointestinal wall. They also raise the possibility that EGC have particular immunosuppressive properties in inflammatory bowel diseases such as Crohn's disease. Copyright © 2016. Published by Elsevier B.V.

  13. Nonadherence to immunosuppression: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Moreso F

    2015-06-01

    Full Text Available Francesc Moreso,1 Irina B Torres,1 Gemma Costa-Requena,2 Daniel Serón1 1Nephrology Department, 2Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, Barcelona, Spain Abstract: Nonadherence to immunosuppressant treatment is common after renal transplantation involving >20% of patients. It is associated with cellular rejection, appearance of donor-specific antibodies, and chronic rejection. It has been estimated that nonadherence can be detected in approximately 50% of failing grafts. Since the evaluation of sociodemographic factors do not allow characterizing the target population, it is necessary to combine different measures of adherence (self-reporting and collateral reporting, pill counts, biological monitoring of blood samples, or others to increase its diagnostic accuracy. During the last decade, it has been shown that the implementation of a multidimensional intervention including information, motivation, and behavioral interventions may lead to an improvement of adherence to treatment. On the other hand, it has been shown that one-off feedback from a nurse, simplification of treatment, or financial assistance programs offered little improvement. Thus, increasing the effectiveness of adherence interventions might have a far greater impact on the long-term outcome of renal transplants than any improvement in specific medical treatments. This will require coordinated action from health professionals, researchers, health planners, and policy makers. Keywords: renal transplantation, nonadherence, immunosuppressive treatment

  14. Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

    Czech Academy of Sciences Publication Activity Database

    Hájková, Michaela; Heřmánková, Barbora; Javorková, Eliška; Boháčová, Pavla; Zajícová, Alena; Holáň, Vladimír; Krulová, Magdaléna

    2017-01-01

    Roč. 13, č. 1 (2017), s. 104-115 ISSN 1550-8943 R&D Projects: GA ČR(CZ) GA14-12580S; GA MŠk(CZ) LO1508; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : mesenchymal stem cells * immunosuppressive drugs * stem cell therapy Subject RIV: FF - HEENT, Dentistry OBOR OECD: Immunology Impact factor: 2.967, year: 2016

  15. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

    Science.gov (United States)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

    2012-07-05

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

  16. Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

    Science.gov (United States)

    Walzer, P D; Foy, J; Runck, J; Steele, P; White, M; Klein, R S; Otter, B A; Sundberg, R J

    1994-01-01

    Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships. PMID:7872750

  17. Clinical aspects of immunosuppression in poultry

    Directory of Open Access Journals (Sweden)

    Rеsаnоvić Rаdmilа

    2015-01-01

    Full Text Available Immunity is ability to stop an infection. Immunosupression is a status where the immunity is reduced. Humoral (antibodies and/or cell immunity may be depressed. Immunosupression can be caused by infectious agents, improper feeding balance (deficiencies, lack of biosecurity, management failures, stress or by a combination of these factors. Each of these possible causes must be seriously worked out to prevent the consequences of immunosupression on profitability. Environmental factors and numerous infectious pathogens have been identified as a multi-factorial cause of various degrees of immunosupression. Mainly subclinical character and coinfections make the diagnosis of the primary immunosuppressive agents difficult. On the other hand, early diagnosis and identification of contributing factors are important to develop strategies to fight immunosupression in birds successfully. A combination of biosecurity measures, optimized housing condition and stress reduction together with appropriate vaccination strategies is necessary for the successful control of immunosupression in commercial poultry.

  18. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  19. Viruses in cancers among the immunosuppressed.

    Science.gov (United States)

    Arroyo Mühr, Laila Sara; Bzhalava, Zurab; Hortlund, Maria; Lagheden, Camilla; Nordqvist Kleppe, Sara; Bzhalava, Davit; Hultin, Emilie; Dillner, Joakim

    2017-12-15

    Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably nonmelanoma skin carcinoma (NMSC). We followed all 13,429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). The sequences were analyzed for viruses based on two bioinformatics algorithms (paracel-blast (sensitive for detection of known viruses) and hidden Markov model (HMM; sensitive for distantly related viruses)). Among the 62 NMSCs, the virus family detected in the largest proportion of specimens was Mimiviridae (9/62 NMSCs). The majority of the virus-related reads belonged to Papillomaviridae. The HMM analysis identified 86 additional previously not described viral contigs related to 11 virus families, with reads related to Mimiviridae being the most common (detected in 28/62 NMSCs) with the most prevalent contig (Mimivirus SE906, 1937 bp) detected in 17/62 NMSCs. Among the 27 other cancers, viral sequences were detected in only 5 specimens by blast analysis, compared to in all 27 specimens by HMM (Mimiviridae, Poxviridae, Phycodnaviridae and virus-related sequences yet unclassified to any family). 99% of the virus reads belonged to a single previously not described sequence (Mimivirus SE996, 911 bp). A multitude of viruses is readily detectable in specimens with cancers occurring among the immunosuppressed, with sequences related to Mimiviridae being the most prevalent. Further research would be needed to elucidate the biological significance of the viruses. © 2017 UICC.

  20. Menopause in women with chronic immunosuppressive treatment – how to help those patients

    Directory of Open Access Journals (Sweden)

    Anna Cyganek

    2016-03-01

    Full Text Available Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

  1. Menopause in women with chronic immunosuppressive treatment - how to help those patients.

    Science.gov (United States)

    Cyganek, Anna; Pietrzak, Bronisława; Wielgoś, Mirosław; Grzechocińska, Barbara

    2016-03-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

  2. Kidney transplant from a living monozygotic twin donor with no maintenance immunosuppression.

    Science.gov (United States)

    Sánchez-Escuredo, Ana; Barajas, Alberto; Revuelta, Ignacio; Blasco, Miquel; Cofan, Federic; Esforzado, Núria; Ricart, María José; Torregrosa, Vicens; Campistol, Josep Maria; Oppenheimer, Federic; Diekmann, Fritz

    2015-01-01

    From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

  3. [52-year-old patient with subcutaneous space-occupying lesion in immunosuppression].

    Science.gov (United States)

    Kolligs, F T; Gerbes, A L; Dürr, E M; Schauer, R; Kessler, M; Jelinek, T; Löscher, T; Bilzer, M

    2003-06-01

    We report the case of a 52-years-old male patient, who was diagnosed with subcutaneous alveolar echinococcosis 6 months after liver transplantation for HCV-related cirrhosis. Nether the explanted nor the transplantated liver revealed an echinococcus focus. Therefore a rare primary extrahepatic manifestation was likely. Interestingly, the echinococcal larvae had developed protoscolices. The development of mature tapeworms in human is a rarity, which could be related to the immunosuppressive therapy after liver transplantation. The patient was curatively treated by surgical removal of the subcutaneous tumor and a postoperative therapy with albendazole. Furthermore, HCV reinfection (genotype 2b) was successfully treated with interferone alpha 2b and ribavirine for 6 months.

  4. Cytomegalovirus Infection Impairs Immunosuppressive and Antimicrobial Effector Functions of Human Multipotent Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Roland Meisel

    2014-01-01

    Full Text Available Human mesenchymal stromal cells (MSC possess immunosuppressive and antimicrobial effects that are partly mediated by the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO. Therefore MSC represent a promising novel cellular immunosuppressant which has the potential to control steroid-refractory acute graft versus host disease (GvHD. In addition, MSC are capable of reducing the risk of infection in patients after haematopoietic stem cell transplantation (HST. Recent data indicate that signals from the microenvironment including those from microbes may modulate MSC effector functions. As Cytomegalovirus (CMV represents a prominent pathogen in immunocompromised hosts, especially in patients following HST, we investigated the impact of CMV infection on MSC-mediated effects on the immune system. We demonstrate that CMV-infected MSC lose their cytokine-induced immunosuppressive capacity and are no longer able to restrict microbial growth. IDO expression is substantially impaired following CMV infection of MSC and this interaction critically depends on intact virus and the number of MSC as well as the viral load. Since overt CMV infection may undermine the clinical efficacy of MSC in the treatment of GvHD in transplant patients, we recommend that patients scheduled for MSC therapy should undergo thorough evaluation for an active CMV infection and receive CMV-directed antiviral therapy prior to the administration of MSC.

  5. New puzzles for the use of non-invasive ventilation for immunosuppressed patients.

    Science.gov (United States)

    Barbas, Carmen Sílvia Valente; Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled "Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial", which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future.

  6. Posterior Reversible Encephalopathy Syndrome and Fatal Cryptococcal Meningitis After Immunosuppression in a Patient With Elderly Onset Inflammatory Bowel Disease.

    Science.gov (United States)

    Vasant, Dipesh H; Limdi, Jimmy K; Borg-Bartolo, Simon P; Bonington, Alec; George, Regi

    2016-08-01

    Advanced age and associated comorbidities are-recognized predictors of life-threatening adverse outcomes, such as opportunistic infection following immunosuppressive therapy. We describe the case of an elderly patient with stricturing colonic Crohn's disease and significant clinical comorbidities, initially controlled with corticosteroid induction followed by infliximab, whose course was complicated by fatal disseminated cryptococcal infection and posterior reversible encephalopathy syndrome. Our patient's case highlights rare, but serious, complications of immunosuppression. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this potentially vulnerable group, maximizing benefit and minimizing harm.

  7. Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

    2004-01-01

    A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...... indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case...

  8. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  9. Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

    2015-10-29

    Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

  10. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Kirby Sean

    2012-03-01

    Full Text Available Abstract Background After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications. Methods A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications. Results The incidence of neoplasia on lung biopsy was 0.4% (9 cases, which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases, and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2% cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03. Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns. Conclusions Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with

  11. Predictors of Immunosuppressive Regulatory T Lymphocytes in Healthy Women

    International Nuclear Information System (INIS)

    Hampras, S. S.; Nesline, M.; Davis, W.; Moysich, K. B.; Wallace, P. K.; Odunsi, K.; Furlani, N.

    2012-01-01

    Immunosuppressive regulatory T (Treg) cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and Bio Repository (DBBR) program at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood levels of CD4 + CD25 + FOXP3 + Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI), and hormone replacement therapy (HRT) were found to be significant positive predictors of Treg cell levels in peripheral blood (π≤0.05 ). Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (π<0.05) negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.

  12. Immunosuppression during Rhizobium-legume symbiosis.

    Science.gov (United States)

    Luo, Li; Lu, Dawei

    2014-01-01

    Rhizobium infects host legumes to elicit new plant organs, nodules where dinitrogen is fixed as ammonia that can be directly utilized by plants. The nodulation factor (NF) produced by Rhizobium is one of the determinant signals for rhizobial infection and nodule development. Recently, it was found to suppress the innate immunity on host and nonhost plants as well as its analogs, chitins. Therefore, NF can be recognized as a microbe/pathogen-associated molecular pattern (M/PAMP) like chitin to induce the M/PAMP triggered susceptibility (M/PTS) of host plants to rhizobia. Whether the NF signaling pathway is directly associated with the innate immunity is not clear till now. In fact, other MAMPs such as lipopolysaccharide (LPS), exopolysaccharide (EPS) and cyclic-β-glucan, together with type III secretion system (T3SS) effectors are also required for rhizobial infection or survival in leguminous nodule cells. Interestingly, most of them play similarly negative roles in the innate immunity of host plants, though their signaling is not completely elucidated. Taken together, we believe that the local immunosuppression on host plants induced by Rhizobium is essential for the establishment of their symbiosis.

  13. Immunosuppressive mechanisms in protein-calorie malnutrition

    International Nuclear Information System (INIS)

    Redmond, H.P.; Shou, J.; Kelly, C.J.; Schreiber, S.; Miller, E.; Leon, P.; Daly, J.M.

    1991-01-01

    Protein-calorie malnutrition (PCM) induces immunosuppression leading to increased mortality rates. Impaired macrophage respiratory burst activity (superoxide anion [O2-] generation) occurs in PCM, but cellular mechanisms are unclear. The major pathway resulting in O2- production involves inositol lipid-dependent signal transduction. This study examined the effect of mild versus severe PCM on macrophage O2- generating signal transduction pathways specific for responses to Candida albicans. Mice (CFW/Swiss Webster: n = 300) were randomized to either control or low protein diets for 3 or 8 weeks. Peritoneal macrophages were harvested for O2- production, mannose-fucose receptor (MFR) expression, membrane phospholipid analysis, arachidonic acid (AA) content, prostaglandin E2 (PGE2) production, and protein kinase C levels. O2- release was impaired in both mild and severe PCM. MFR expression was also decreased at these time points. Inositol lipid content was significantly lower at the 8-week time point only, although PGE2 and AA were significantly higher in the low protein diet group at 3 weeks. Protein kinase C levels were unchanged by PCM. Thus, mild PCM significantly increases macrophage-PGE2 production secondary to increased AA phospholipid content, with subsequent inhibition of O2- and MFR expression. Severe PCM inhibits macrophage (O2-) through depletion of critical membrane phospholipid components with subsequent impairment in signal transduction

  14. Imunossupressores na Dermatologia Immunosuppressive agents in Dermatology

    Directory of Open Access Journals (Sweden)

    Aline Lopes Bressan

    2010-02-01

    Full Text Available Os imunossupressores são drogas que agem na divisão celular e têm propriedades anti-inflamatórias. Sendo assim, são essencialmente prescritos na prevenção de rejeição de transplantes e no tratamento das doenças autoimunes e inflamatórias crônicas, que, na Dermatologia, têm a psoríase como maior representante. Nesta sessão serão descritas as principais drogas imunossupressoras, com orientações para seu manejo adequado.Immunosupressants are drugs that act in cell division and have anti-inflammatory effects. Therefore, they are essentially prescribed in the prevention of transplant rejection and in the treatment of autoimmune disorders and chronic inflammatory diseases, whose main example in Dermatology is psoriasis. In this work the most important immunosuppressive drugs and orientation to properly administer them are going to be described.

  15. Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential

    Directory of Open Access Journals (Sweden)

    Jeffery J. Auletta

    2011-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs possess immunomodulatory properties that make them attractive therapeutic alternatives. We evaluated the in vitro immunosuppressive activity of medium conditioned by human MSCs from 5 donors expanded 13 passages with or without FGF-2. FGF-2 supplementation increased expansion 3,500- and 240,000-fold by passages 7 and 13, respectively. There were no differences in immunosuppressive activity between media conditioned by passage-matched cells expanded under different conditions, but media conditioned by FGF-treated MSCs were superior to population doubling-matched controls. The immunosuppressive activity was maintained in three of the preparations but decreased with expansion in two. The proliferation induced by FGF-2 did not result in loss of immunosuppressive activity. However, because the immunosuppressive activity was not consistently preserved, caution must be exercised to ensure that the activity of the cells is sufficient after extensive expansion.

  16. Influenza vaccines in immunosuppressed adults with cancer.

    Science.gov (United States)

    Bitterman, Roni; Eliakim-Raz, Noa; Vinograd, Inbal; Zalmanovici Trestioreanu, Anca; Leibovici, Leonard; Paul, Mical

    2018-02-01

    This is an update of the Cochrane review published in 2013, Issue 10.Immunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population are lacking, and the value of vaccination in this population remains unclear. To assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalisations, influenza-related mortality and immunogenicity were defined as secondary outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and LILACS databases up to May 2017. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (haematological), and ASCO (oncological) between the years 2006 to 2017. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases. Randomised controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) haematopoietic stem cell transplantation (HSCT). Two review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane

  17. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

    Science.gov (United States)

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

    2016-10-15

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Irradiation of ice creams for immunosuppressed patients

    International Nuclear Information System (INIS)

    Adeil Pietranera, Maria S.; Narvaiz, Patricia; Horack, C.; Kairiyama, Eulogia; Gimenez, Palmira; Gronostajski, D.

    2003-01-01

    Immunosuppressed patients are very likely to acquire microbial food borne diseases, since due to illness, biological condition or situations generating risks, their natural defences are below what is considered as 'normal limits'. This makes their food intake very restricted, avoiding all those products that could be a source of microorganisms. Gamma radiation applied at sub-sterilizing doses represents a good choice in order to achieve 'clean' diets, and at the same time, it can widen the variety of available meals for these patients, allowing the inclusion of some products normally considered as 'high risk' due to their microbial load, but that can be nutritionally or psychologically adequate. One of these products is ice-cream, a minimally processed type of meal that does not suffer enough microbial inactivation during its processing. Particularly those from natural origin can carry undesirable contamination causing sometimes diseases to the consumer. For that reason, different ice-cream flavours (vanilla, raspberry, peach and milk jam) were exposed to an irradiation treatment at the 60 Co facility of the Ezeiza Atomic Centre. The delivered doses were 3, 6 and 9 kGy. Microbiological determinations were performed, together with sensory evaluations and some chemical analysis: acidity, peroxide value, ultraviolet and visible absorption, thin-layer chromatography and sugar determination, in order to find out if gamma radiation could be applied as a decontamination process without impairing quality. Water-based ice-creams (raspberry and peach) were more resistant to gamma radiation than cream-based ones (vanilla and milk jam), due to their differences in fat content. Gamma irradiation with 3 kGy reduced remarkably the microbial load of these ice-creams and eliminated pathogens without impairing their quality. (author)

  19. Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study.

    Science.gov (United States)

    Hu, Stephen Chu-Sung; Yen, Feng-Lin; Wang, Tsu-Nai; Lin, Yu-Chih; Lin, Chi-Ling; Chen, Gwo-Shing

    2016-07-01

    The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined. We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants. A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development. Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose. This study is retrospective in nature. Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006.

    Science.gov (United States)

    Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Webster, Angela C; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

    2015-11-01

    Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p heart and lung recipients (p heart and lung recipients (p transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Immunosuppression during viral oncogenesis. V. Resistance to virus-induced immunosuppressive factor.

    Science.gov (United States)

    Strayer, D S; Dombrowski, J

    1988-07-01

    Rabbits given malignant rabbit fibroma virus (MV) develop severe immunologic dysfunction during the course of infection. Splenic T lymphocytes from these rabbits elaborate a soluble non-specific immunosuppressive factor (virus-induced suppressor factor (VISF]. As malignant rabbit fibroma virus infection progresses, normal immunologic responsiveness returns. This recovery is multi-factorial and involves production by T lymphocytes of a soluble factor capable of antagonizing the activity of VISF. This soluble anti-suppressor factor (ASF) is not a generalized immunologic potentiator. Its sole apparent effect on immune function appears to be to antagonize the activity of VISF. The protective effects of ASF are evident only when suppressor factors and ASF are simultaneously present in culture. Pre-treatment of target cells with ASF-containing culture supernatants does not render them insensitive to the immunosuppressive effects of subsequent treatment with VISF. In addition, ASF appears to be directly responsible for antagonizing VISF activity. That is, ASF does not appear to initiate an anti-suppressive cascade by activating a population of cells that in turn generate secondary protective factors. ASF-producing cells do not bind Vicia villosa lectin, as do contra-suppressor cells described by others. In almost all of these features, the system we describe herein differs from systems in which other investigators have described factors that antagonize the effects of suppressor factors.

  2. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation

    DEFF Research Database (Denmark)

    McAlister, V C; Haddad, E; Renouf, E

    2006-01-01

    A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were...

  3. Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn

    NARCIS (Netherlands)

    Lowenberg, M; Tuynman, J; Bilderbeek, J; Gaber, T; Buttgereit, F; van Deventer, S; Peppelenbosch, M; Hommes, D

    2005-01-01

    Glucocorticoids (GCs) are effective immunosuppressive agents and mediate well-defined transcriptional effects via GC receptors. There is increasing evidence that GCs also initiate rapid nongenomic signaling events. Using activated human CD4(+) lymphocytes and a peptide array containing 1176

  4. Inferior results with basis immunosuppression with sirolimus in kidney transplantation.

    NARCIS (Netherlands)

    Akker, J.M. van den; Hene, R.J.; Hoitsma, A.J.

    2007-01-01

    BACKGROUND: The introduction of sirolimus has provided the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors. METHODS: We conducted a first trial in 30 renal allograft recipients. Ten patients were followed prospectively and received sirolimus, to

  5. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

    Science.gov (United States)

    Salinas-Carmona, Mario Cesar; Rosas-Taraco, Adrian Geovanni; Welsh, Oliverio

    2012-10-01

    Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma.

  6. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.L.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  7. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.S.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  8. Birth defects in juvenile Wistar rats after exposure to immunosuppressive drugs during pregnancy.

    Science.gov (United States)

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Pilutin, Anna; Safranow, Krzysztof; Kosik-Bogacka, Danuta; Baranowska-Bosiacka, Irena; Gołembiewska, Edyta; Kędzierska, Karolina; Domański, Leszek; Ciechanowski, Kazimierz

    2017-01-01

    Immunosuppressive drugs and their active metabolites can cross the placental barrier and enter fetal circulation. The adverse effects on the fetus include chromosomal aberrations, structural malformations, organ-specific toxicity and intrauterine growth retardation. The aim of our study was to investigate the impact of "safe" and "contraindicated" immunosuppressive drugs on birth defects in juvenile Wistar rats after exposure of pregnant female rats to these drugs. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Treatment with mycophenolate mofetil and everolimus turned out to be toxic. We have noticed a significantly reduced number of live births in all pregnant rats exposed to these drugs in combination with calcineurin inhibitors and prednisone. Malformations and histological changes of fetal organs were confirmed after mycophenolate mofetil exposure during pregnancy. Mycophenolate mofetil turned out to be more toxic when used with tacrolimus than with cyclosporin (delivery of live offspring was possible only in the latter group). Everolimus in combination with cyclosporin effectively suppressed the fetal maturation in utero, but did not contribute to the development of malformations.

  9. Incidence of herpes zoster amongst adults varies by severity of immunosuppression.

    Science.gov (United States)

    Schröder, Carsten; Enders, Dirk; Schink, Tania; Riedel, Oliver

    2017-09-01

    We examined the incidence of herpes zoster in immunocompromised adults (≥18 years) with different severities of immunosuppression and assessed the prevalence of complications and of various kinds of healthcare resource utilisation. German claims data from more than ten million adults were used to calculate annual incidence rates of herpes zoster for the years 2006-2012 and to analyse the prevalence of complications, physician visits, hospitalisations, and antiviral and analgesic treatments using a cohort design. The analyses were stratified by age, sex, and severity of immunosuppression, defined by immunocompromising conditions and drug therapies. The incidence rate per 1000 person-years of herpes zoster was almost twice as high in immunocompromised patients (11.5 (95% confidence interval (CI): 11.4-11.6)) compared to immunocompetent subjects (5.9 (95% CI: 5.8-5.9)). The incidence rate was higher in highly immunocompromised patients (13.4 (95% CI: 13.2-13.6)) than in patients with a low severity of immunosuppression (10.0 (95% CI: 9.8-10.1)). These differences were observed for both sexes and in all age groups. Complications, outpatient physician visits, hospitalisations, and analgesic treatments occurred more frequently in immunocompromised patients as well. Our results show that immunocompromised individuals are affected by the disease in particular and that the burden of herpes zoster is highest in severely immunocompromised patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  10. Clinical Trial of FK 506 Immunosuppression in Adult Cardiac Transplantation

    OpenAIRE

    Armitage, John M.; Kormos, Robert L.; Morita, Shigeki; Fung, John; Marrone, Gary C.; Hardesty, Robert L.; Griffith, Bartley P.; Starzl, Thomas E.

    1992-01-01

    The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparabl...

  11. CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Nicolas Espagnolle

    2017-04-01

    Full Text Available Summary: Mesenchymal stromal cells (MSCs sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therapy

  12. Role of microsatellite instability, immunohistochemistry and mismatch repair germline aberrations in immunosuppressed transplant patients: a phenocopy dilemma in Muir-Torre syndrome.

    Science.gov (United States)

    Ponti, Giovanni; Manfredini, Marco; Pellacani, Giovanni; Tomasi, Aldo

    2016-11-01

    Sebaceous tumours and keratoacanthomas are uncommon neoplasms that constitute important clinical criteria for Muir-Torre syndrome (MTS) diagnosis. In MTS patients, the increased risk of developing synchronous or metachronous visceral malignancies is characterised by autosomal dominant inheritance. However, there are further conditions, other than MTS, that increase the risk of sebaceous neoplasms, e.g. iatrogenic immunosuppression. In this latter scenario, the sebaceous tumours can present microsatellite instability (MSI) and loss of mismatch repair (MMR) proteins, characteristic of hereditary syndromes, even in the absence of MMR germline mutations. In this article, we examine transplant probands in which the immunosuppressive therapies unmask the MTS cutaneous phenotypes, showing MSI and loss of MMR protein expression, as demonstrated by immunohistochemistry (IHC). Furthermore, MMR genes sequencing analysis identified the presence of germline mutations in MTS-suspected individuals, in the absence of a visceral MTS phenotype. It is well known that immunosuppression plays a central role in the development of sebaceous tumours in both MTS and in non-syndromic settings. Sebaceous skin tumours' MSI status and IHC profiles can be influenced by epigenetic or iatrogenic factors; however, they constitute valuable tools and a cost-effective approach to screen individuals who otherways should undergo MMR genes direct sequencing in the context of immunosuppression. In this complex setting, the choice of the immunosuppressive drug becomes a critical decision for the management of both MTS and sporadic transplant patients, which may benefit from the administration of immunosuppressive drugs, resulting in a low impact on skin cancerogenesis.

  13. Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent  Clostridium difficile Infection

    Directory of Open Access Journals (Sweden)

    Hadeel Zainah

    2012-01-01

    Full Text Available We report a case of ulcerative colitis (UC and recurrent Clostridium difficile infection (CDI where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.

  14. Immunosuppression in pregnant women with systemic lupus erythematosus.

    Science.gov (United States)

    Ponticelli, Claudio; Moroni, Gabriella

    2015-05-01

    Most pregnancies are successful in women with systemic lupus erythematosus, particularly if the disease is quiescent and there are no signs of active nephritis. There is no major impact of immunosuppression on maternal outcome. However, high doses of cyclosporine and glucocorticoids are used which may favor development of hypertension or preeclampsia. Some immunosuppressive drugs may exert toxic effects on the fetus. Glucocorticoids may cause small birth weight, and azathioprine and calcineurin inhibitors may be associated with lower birth weight, gestational age and prematurity. Cyclophosphamide may cause fetal malformation when given in the first trimester. Mycophenolate and leflunomide are teratogenic drugs and should be withdrawn before conception in case of programmed pregnancy or should be rapidly discontinued in case of unexpected pregnancy. Option counseling for pregnancy and correct use of immunosuppressive drugs are prerequisites for a successful pregnancy in women with lupus.

  15. New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps

    Science.gov (United States)

    Mi, Jia-Ning; Han, Yuwei; Xu, Yingqiong; Kou, Junping; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-01-01

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps. PMID:27966660

  16. The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients.

    Science.gov (United States)

    Bernat-García, J; Morales Suárez-Varela, M; Vilata-Corell, J J; Marquina-Vila, A; Pallardo, L; Crespo, J

    2014-12-01

    Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs. Copyright © 2014. Published by Elsevier Espana.

  17. Down-regulated NOD2 by immunosuppressants in peripheral blood cells in patients with SLE reduces the muramyl dipeptide-induced IL-10 production.

    Directory of Open Access Journals (Sweden)

    Shui-Lian Yu

    Full Text Available BACKGROUND: Pattern recognition receptors (PRRs such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs in systemic lupus erythematosus (SLE patients, for playing immunopathological roles. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the expression and function of the PRR nucleotide-binding oligomerization domain (NOD2 in SLE. NOD2 expression in T, B lymphocytes, monocytes, myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs was assessed in SLE patients and healthy controls (HCs using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon NOD2 agonist muramyl dipeptide (MDP stimulation was assessed using Cytometric Bead Array. Over-expression of NOD2 in monocytes was observed in immunosuppressant naïve SLE patients, and was positively associated with longer disease duration. Immunosuppressive therapy was an independent explanatory variable for downregulating NOD2 expression in CD8+ T, monocytes, mDCs and pDCs. Ex vivo basal productions of cytokines (IL-6, IL-8 and IL-10 were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (% of cytokines (IL-1β from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (% of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs. CONCLUSIONS/SIGNIFICANCE: Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the

  18. Cutaneous Alternaria infectoria infection in a dog in association with therapeutic immunosuppression for the management of immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Dedola, C.; Stuart, A.P.G.; Ridyard, A.E.; Else, R.W.; Van den Broek, T.; Choi, J.S.; de Hoog, G.S.; Thoday, K.L.

    2010-01-01

    A 4-year-old, ovariohysterectomized, English springer spaniel on immunosuppressive therapy was re-examined for the review of its immune-mediated haemolytic anaemia and the recent development of skin lesions. For the 3 months since hospital discharge, the dog had been receiving 1.3 mg/kg prednisolone

  19. Association of HIV-Induced Immunosuppression and Clinical ...

    African Journals Online (AJOL)

    Association of HIV-Induced Immunosuppression and Clinical Malaria in Nigerian Adults. ... African Journal of Infectious Diseases ... Abstract. Despite the growing body of evidence on the interaction between HIV and malaria in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV-infected patients in Nigeria.

  20. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    Science.gov (United States)

    Goldberg, Diana R.; Yuill, Thomas M.; Burgess, E.C.

    1990-01-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  1. Balance between herpes viruses and immunosuppression after lung transplantation

    NARCIS (Netherlands)

    Verschuuren, Erik Alfons Maria

    2006-01-01

    This thesis focuses on the interplay between two Herpes Virus infections and the immunosuppression used after solid organ (and especially lung) transplantation. It starts with the description of diagnostic tools of Cytomegalovirus (CMV) and their therapeutic implications. Then it addresses the major

  2. Survival predictors in paraquat intoxification and role of immunosuppression

    Directory of Open Access Journals (Sweden)

    Keng-Hee Koh

    2014-01-01

    In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4% compared to historical control (30 out of 52 patients (57.7% (p = 0.885 in those with eGFR > 50 ml/min/1.73 m2 or WBC 11,000/μL.

  3. Candida meningitis in a suspected immunosuppressive patient - A ...

    African Journals Online (AJOL)

    Candida meningitis in a suspected immunosuppressive patient - A case report. EO Sanya, NB Ameen, BA Onile. Abstract. No Abstract. West African Journal of Medicine Vol. 25 (1) 2006: pp.79-81. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  4. A tacrolimus-related immunosuppressant with reduced toxicity.

    Science.gov (United States)

    Dumont, F J; Koprak, S; Staruch, M J; Talento, A; Koo, G; DaSilva, C; Sinclair, P J; Wong, F; Woods, J; Barker, J; Pivnichny, J; Singer, I; Sigal, N H; Williamson, A R; Parsons, W H; Wyvratt, M

    1998-01-15

    Tacrolimus (FK506) has potent immunosuppressive properties reflecting its ability to block the transcription of lymphokine genes in activated T cells through formation of a complex with FK506 binding protein-12, which inhibits the phosphatase activity of calcineurin. The clinical usefulness of tacrolimus is limited, however, by severe adverse effects, including neurotoxicity and nephrotoxicity. Although this toxicity, like immunosuppression, appears mechanistically related to the calcineurin inhibitory action of the drug, a large chemistry effort has been devoted to search for tacrolimus analogs with reduced toxicity but preserved immunosuppressive activity that might have enhanced therapeutic utility. Here, we report on the identification of such an analog, which was synthetically derived from ascomycin (ASC), the C21 ethyl analog of tacrolimus, by introducing an indole group at the C32 position. The profile of biological activity of indolyl-ASC was characterized in rodent models of immunosuppression and toxicity. Indolyl-ASC was found to exhibit an immunosuppressive potency equivalent to that of tacrolimus in T-cell activation in vitro and in murine transplant models, even though indolyl-ASC bound about 10 times less to intracellular FK506 binding protein-12 than tacrolimus or ASC. Further evaluation of indolyl-ASC revealed that it is threefold less potent than tacrolimus in inducing hypothermia, a response that may reflect neurotoxicity, and in causing gastrointestinal transit alterations in mice. Moreover, indolyl-ASC was at least twofold less nephrotoxic than tacrolimus upon 3-week oral treatment in rats. Altogether, these data indicate a modest but definite improvement in the therapeutic index for indolyl-ASC compared with tacrolimus in rodent models.

  5. Early Introduction of Everolimus Immunosuppressive Regimen in Liver Transplantation with Extra-Anatomic Aortoiliac-Hepatic Arterial Graft Anastomosis

    Directory of Open Access Journals (Sweden)

    Emanuele Felli

    2014-01-01

    Full Text Available Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease, when no other medical treatment is possible. Despite high rates of 1- to 5-year survival, long-term adverse effects of immunosuppressant agents remain of major concern. Current research and clinical efforts are made to develop immunosuppressant agents that minimize adverse effects along with a low rate of graft rejection. Tailoring immunosuppressive therapy to individual patients by the use of proliferation signal inhibitors seems to be the best way to minimize toxicity and increase efficacy. Recently everolimus has been introduced in clinical practice; among its adverse effects an increased incidence of arterial graft thrombosis in renal transplants, vascular anastomosis leakage, impaired wound healing, and thrombotic microangiopathy have been reported. We present the case of a 54-year-old patient submitted to liver transplantation for end-stage liver disease treated by an extra-anatomic aortoiliac-hepatic arterial graft anastomosis and early postoperative introduction of everolimus for acute renal failure. Postoperative period was characterized by two abdominal collections and reactivation of cytomegalovirus infection that were treated by percutaneous drainage and antiviral therapy, respectively; the patient is well after 8-month followup with patency of the arterial conduit and no leakage.

  6. Cost utility analysis of immunosuppressive regimens in adult renal transplant recipients in England and Wales

    Directory of Open Access Journals (Sweden)

    Muduma G

    2014-11-01

    Full Text Available Gorden Muduma,1 Jane Shaw,2 Warren M Hart,3 Abayomi Odeyemi,3 Isaac Odeyemi21Astellas Pharma Europe Limited, Chertsey, UK; 2Astellas Pharma Limited, Chertsey, UK; 3EcoStat Consulting UK Limited, London, UKBackground: End-stage renal disease is the irreversible final stage of chronic kidney disease and is fatal when not managed by either transplantation or dialysis. Transplantation is generally preferred over dialysis. However, to prevent graft rejection or loss, lifelong immunosuppression is required. Tacrolimus is currently the cornerstone of post-transplantation immunosuppression. The study aim was to carry out an economic evaluation of immunosuppression, including more recent agents such as a once-daily prolonged-release formulation of tacrolimus (Advagraf™ and belatacept, relative to a twice-daily immediate-release formulation of tacrolimus (Prograf™.Methods: A model was constructed comprising six states: onset of biopsy-confirmed acute rejection, functioning graft with or without a biopsy-confirmed acute rejection, non-functioning graft (dialysis, re-transplantation, and death. Data on clinical effectiveness were derived from a systematic literature review and the model captured the effects of patient adherence to immunosuppressant therapy on graft survival using relative risk of graft survival and published data on adherence in patients using Advagraf and Prograf. In the base case, the time horizon was 25 years and one-way and probabilistic sensitivity analyses were conducted.Results: The analysis demonstrated that Prograf was cost-effective when compared with cyclosporin and belatacept and was more effective than sirolimus, but would not be considered cost-effective against sirolimus. The modeled improvement in the adherence profile of patients using Advagraf relative to Prograf resulted in both improved clinical outcomes and reduced costs. Conclusion: Prograf was more clinically effective than cyclosporin, belatacept, and sirolimus

  7. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  8. Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease.

    Science.gov (United States)

    Renna, Sara; Cottone, Mario; Orlando, Ambrogio

    2014-08-07

    Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn's disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical

  9. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care.

    Science.gov (United States)

    Gentile, Lori F; Cuenca, Alex G; Efron, Philip A; Ang, Darwin; Bihorac, Azra; McKinley, Bruce A; Moldawer, Lyle L; Moore, Frederick A

    2012-06-01

    Surgical intensive care unit (ICU) stay of longer than 10 days is often described by the experienced intensivist as a "complicated clinical course" and is frequently attributed to persistent immune dysfunction. "Systemic inflammatory response syndrome" (SIRS) followed by "compensatory anti-inflammatory response syndrome" (CARS) is a conceptual framework to explain the immunologic trajectory that ICU patients with severe sepsis, trauma, or emergency surgery for abdominal infection often traverse, but the causes, mechanisms, and reasons for persistent immune dysfunction remain unexplained. Often involving multiple-organ failure (MOF) and death, improvements in surgical intensive care have altered its incidence, phenotype, and frequency and have increased the number of patients who survive initial sepsis or surgical events and progress to a persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Often observed, but rarely reversible, these patients may survive to transfer to a long-term care facility only to return to the ICU, but rarely to self-sufficiency. We propose that PICS is the dominant pathophysiology and phenotype that has replaced late MOF and prolongs surgical ICU stay, usually with poor outcome. This review details the evolving epidemiology of MOF, the clinical presentation of PICS, and our understanding of how persistent inflammation and immunosuppression define the pathobiology of prolonged intensive care. Therapy for PICS will involve innovative interventions for immune system rebalance and nutritional support to regain physical function and well-being. Copyright © 2012 by Lippincott Williams & Wilkins.

  10. Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction.

    Science.gov (United States)

    Gharagozloo, Marjan; Majewski, Slawomir; Foldvari, Marianna

    2015-05-01

    Autoimmune diseases are chronic, destructive diseases that can cause functional disability and multiple organ failure. Despite significant advances in the range of therapeutic agents, especially biologicals, limitations of the routes of administration, requirement for frequent long-term dosing and inadequate targeting options often lead to suboptimal effects, systemic adverse reactions and patient non-compliance. Nanotechnology offers promising strategies to improve and optimize autoimmune disease treatment with the ability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we focus on nanomedicine-based delivery strategies of biological immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis and type 1 diabetes. This comprehensive review details the concepts and clinical potential of novel nanomedicine approaches for inducing immunosuppression and immunological tolerance in autoimmune diseases in order to modulate aberrant and pathologic immune responses. The treatment of autoimmune diseases remains a significant challenge. The authors here provided a comprehensive review, focusing on the current status and potential of nanomedicine-based delivery strategies of immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type 1 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Airway cellular response to two different immunosuppressive regimens in lung transplant recipients

    NARCIS (Netherlands)

    Slebos, DJ; Kauffman, H F; Koeter, GH; Verschuuren, Erik A M; van der Bij, W; Postma, DS

    A number of new immunosuppressive drugs have become available in transplant medicine. We investigated the effects of two different immunosuppressive protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung transplant recipients who were treated with anti-thymocyte globulin

  12. Side Effects of Immunosuppressant Medications as They Affect Physical Fitness: A Physical Therapist's Point of View

    Science.gov (United States)

    ... Death HIV and Kidney Transplantation/Donation Immunosuppressants Incompatible Blood Types and Paired Exchange Programs Knowing Your Immunosuppressive (anti-rejection) Medications The National Kidney Foundation (NKF) is the ...

  13. Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

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    Asami Hanazawa

    2018-02-01

    Full Text Available The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs, and tumor-associated macrophages (TAMs that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg mouse strain, human interleukin (hIL-6-expressing NOG mice (NOG-hIL-6 transgenic mice. After transplantation of human hematopoietic stem cells (HSCs, the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF, and vascular endothelial growth factor (VEGF, into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1, IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory/immunosuppressive

  14. IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

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    E. A. Starikova

    2015-01-01

    Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

  15. Neurologic emergencies in HIV-negative immunosuppressed patients.

    Science.gov (United States)

    Guzmán-De-Villoria, J A; Fernández-García, P; Borrego-Ruiz, P J

    HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Genital Tuberculosis as the Cause of Tuboovarian Abscess in an Immunosuppressed Patient

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    M. Ilmer

    2009-01-01

    Full Text Available Background. Although tuberculosis (TB is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB, and in particular female genital tract infection, remains a rare event. Case Report. A 35-year-old human immunodeficiency virus (HIV seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb. Consequently, antituberculotic therapy was provided. Conclusion. In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present.

  17. Effects of immunosuppressive treatment on protein expression in rat kidney

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    Kędzierska K

    2014-09-01

    Full Text Available Karolina Kędzierska,1 Katarzyna Sporniak-Tutak,2 Krzysztof Sindrewicz,2 Joanna Bober,3 Leszek Domański,1 Mirosław Parafiniuk,4 Elżbieta Urasińska,5 Andrzej Ciechanowicz,6 Maciej Domański,1 Tomasz Smektała,2 Marek Masiuk,5 Wiesław Skrzypczak,6 Małgorzata Ożgo,6 Joanna Kabat-Koperska,1 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology, and Internal Medicine, 2Department of Dental Surgery, 3Department of Medical Chemistry, 4Department of Forensic Medicine, 5Department of Pathomorphology, Pomeranian Medical University, 6Department of Physiology, Cytobiology, and Proteomics, West Pomeranian University of Technology, Szczecin, Poland Abstract: The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents' toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins' synthesis. Very slight differences

  18. Personalization of the Immunosuppressive Treatment in Renal Transplant Recipients: The Great Challenge in “Omics” Medicine

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    Gianluigi Zaza

    2015-02-01

    Full Text Available Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%–5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, “omics” techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient’s genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies.

  19. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

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    Floor M. Garritsen

    2017-03-01

    Full Text Available There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC, including basal cell carcinoma and squamous cell carcinoma (SCC, in patients with atopic dermatitis (AD treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%. The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI 6.5–19.7. Patients developing NMSC were older at the start of therapy (p<0.001 and data lock (p<0.001 compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively. In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

  20. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.

    Science.gov (United States)

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Wojciuk, Bartosz; Wojciechowska-Koszko, Iwona; Roszkowska, Paulina; Krasnodębska-Szponder, Barbara; Paczkowska, Edyta; Safranow, Krzysztof; Gołembiewska, Edyta; Machaliński, Bogusław; Ciechanowski, Kazimierz

    2016-01-01

    In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system - the thymus and the spleen. The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner.

  1. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    International Nuclear Information System (INIS)

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-01-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced

  2. Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Peng, Xia; Luo, Xin; Hou, Jing-Ying; Wu, Shu-Yun; Li, Liang-Zong; Zheng, Ming-Hua; Wang, Ling-Yun

    2017-01-01

    Currently, there are no effective therapeutic agents for patients with primary sclerosing cholangitis (PSC). This study aimed to evaluate the safety and efficiency of immunosuppressive agents (IAs) for the treatment of PSC. The literatures were searched using the following keywords singly or in combination: PSC, treatments, IAs. The primary outcome was defined as the need for liver transplantation or mortality. Two hundred sixty six patients from 7 eligible studies were analyzed. IAs had no remarkable effects on the rate of mortality or liver transplantation (relative risk, RR 1.02, 95% CI 0.58-1.62, p = 0.92). Subgroup analyses showed no significant effect of IAs co-administration therapy (IAs co-administered with ursodeoxycholic acid, IA co-administered with IA; RR 1.41, 95% CI 0.40-4.95, p = 0.60). IAs caused adverse events (AEs) such as diarrhea, abdominal pain, and pruritus (RR 1.81, 95% CI 1.07-3.07, p = 0.03). IAs therapy did not significantly improve markers of liver function except for aspartate transaminase (weighted mean difference -9.76, 95% CI -12.92 to -6.6, p IAs administrated as either monotherapy or combination therapy do not reduce the risk of mortality or liver transplantation. IAs monotherapy is associated with AEs. © 2017 S. Karger AG, Basel.

  3. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment.

    Science.gov (United States)

    Axelrad, Jordan E; Lichtiger, Simon; Yajnik, Vijay

    2016-05-28

    In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.

  4. Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.

    Science.gov (United States)

    Eddleston, M; Wilks, M F; Buckley, N A

    2003-11-01

    Acute paraquat self-poisoning is a significant problem in parts of Asia, the Pacific and the Caribbean. Ingestion of large amounts of paraquat results in rapid death, but smaller doses often cause a delayed lung fibrosis that is usually fatal. Anti-neutrophil ('immunosuppressive') treatment has been recommended to prevent lung fibrosis, but there is no consensus on efficacy. To review the evidence for the use of immunosuppression in paraquat poisoning, and to identify validated prognostic systems that would allow the use of data from historical control studies and the future identification of patients who might benefit from immunosuppression. Systematic review. We searched PubMed, Embase and Cochrane databases for 'paraquat' together with 'poisoning' or 'overdose'. We cross-checked references and contacted experts, and searched on [www.google.com] and [www.yahoo.com] using 'paraquat', 'cyclophosphamide', 'methylprednisolone' and 'prognosis'. We found ten clinical studies of immunosuppression in paraquat poisoning. One was a randomized controlled trial (RCT). Seven used historical controls only; the other two were small (n = 1 and n = 4). Mortality in controls and patients varied markedly between studies. Three of the seven non-RCT controlled studies measured plasma paraquat; analysis using Proudfoot's or Hart's nomograms did not suggest that immunosuppression increased survival in these studies. Of 16 prognostic systems for paraquat poisoning, none has been independently validated in a large cohort. The authors of the RCT have performed valuable and difficult research, but their results are hypothesis-forming rather than conclusive; elsewhere, the use of historical controls is problematic. In the absence of a validated prognostic marker, a large RCT of immunosuppression using death as the primary outcome is required. This RCT should also prospectively test and validate the available prognostic methods, so that future patients can be selected for this and other

  5. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    to evade otherwise effective T-cell responses. A growing number of immune evasion mechanisms have been characterized mainly in solid tumors. In hematological malignancies, less is known about how different immune escape mechanisms influence tumor immune evasion and the extent of their impact on ongoing...... immune responses. The present review highlights the potential role of three well-defined immunosuppressive mechanisms in hematological malignancies: (i) inhibitory T-cell pathways (especially programmed death ligand 1/programmed death 1 (PD-L1/PD-1)), (ii) regulatory immune cells, and (iii) metabolic...

  6. Severe neuro-Behcet's disease treated with a combination of immunosuppressives and a TNF-inhibitor.

    Science.gov (United States)

    Korkmaz, Fatma Nur; Ozen, Gulsen; Ünal, Ali Uğur; Kahraman Koytak, Pınar; Tuncer, Nese; Direskeneli, Haner

    2016-01-01

    Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although

  7. Small intestinal bacterial overgrowth syndrome in children with idiopathic nephritic syndrome treated with immunosuppressive agents

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    Katarzyna Siniewicz-Luzeńczyk

    2016-06-01

    Full Text Available Small intestinal bacterial overgrowth syndrome is defined as an increased number of non-pathogenic bacteria over 105 microorganisms in one millilitre of intestinal contents in the initial part of the small intestine. Predisposing disorders include e.g. drug-induced hypochlorydia, congenital and acquired defects of the gastrointestinal tract, immunodeficiency, severe stress situations as well as intestinal microflora imbalance after immunosuppressive therapy. The aim of the study was to assess the incidence of small intestinal bacterial overgrowth in children receiving cyclosporine A due to idiopathic nephritic syndrome. Material and methods: The study included 20 children (11 girls and 9 boys aged 4–16 years (mean age 8.83 ± 3.75 years, diagnosed with idiopathic nephritic syndrome and treated with cyclosporine for over 3 months. The use of antibiotics or probiotics less than 3 months prior to the study was an exclusion criterion. Serum levels of cyclosporin A were measured in all patients. Hydrogen breath test with lactulose was performed as an additional examination. The exhaled breath was analysed using Gastrolyzer (Bedfont. A minimum increase of 20 hydrogen molecules per million air molecules between the maximum value and the fasting level or values in the first hour of the test was considered as a positive test outcome, indicating small intestinal bacterial overgrowth. Results: Negative result of hydrogen breath test, excluding small intestinal bacterial overgrowth, was observed in all 20 children. Conclusions: The  administration of  second line immunosuppressive agents in children with idiopathic nephritic syndrome does not induce non-pathogenic bacterial multiplication in the small intestine.

  8. Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective-controlled study.

    Science.gov (United States)

    Paredes, Víctor; López-Pintor, Rosa María; Torres, Jesús; de Vicente, Juan Carlos; Sanz, Mariano; Hernández, Gonzalo

    2018-01-01

    The main objective of this prospective study was to evaluate the long-term outcome of implant therapy in liver transplant patients (LTP). The secondary goal was to assess several implant- and patient-dependent variables, such as peri-implantitis (PI), peri-implant mucositis (PIM), bone loss (BL), and immediate postoperative complications. Two groups, including 16 pharmacologically immunosuppressed LTP and 16 matched controls, received 52 and 54 implants, respectively, between 1999 and 2008. After evaluating the postoperative healing, a mean follow-up of more than 8 years was carried out, and radiographic, clinical, and periodontal parameters were recorded to evaluate implant survival and implant- and patient-dependent outcomes. The early postsurgical complications were similar in both groups. Implant survival rate was 100% in the LTP group and 98.15% in the CG. PIM was diagnosed in 35.42% of the implants and 64.29% of the patients of LTP group (LTPG) and in 43.40% of the implants and 56.25% of the patients in the CG. PI was detected in 4.17% of the implants and 7.10% of the patients in the LTPG and in 9.43% of the implants and 18.80% of the patients in the CG. Pharmacologically immunosuppression in liver transplant patients was not a risk factor for implant failure, nor for the incidence of peri-implant diseases. Liver transplant is not a contraindication for dental implant treatment, although these patients should be carefully monitored during follow-up care. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum

    Directory of Open Access Journals (Sweden)

    Yufeng Tian

    2016-05-01

    Full Text Available Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1–2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts’ immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA. In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α, interleukin-1 (IL-1, interleukin-8 (IL-8 and interferon-gamma (IFN-γ. In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL. Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks’ successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear.

  10. Immunosuppression with cyclophosphamide favors reinfection with recombinant Toxoplasma gondii strains

    Directory of Open Access Journals (Sweden)

    Silva L.A.

    2012-08-01

    Full Text Available The aim of this study was to verify the effect of immunosuppression by cyclophosphamide (Cy on susceptibility of BALB/c mice subjected to challenge with recombinant strains of Toxoplasma gondii. Animals were prime infected with the D8 (recombinant I/III or the ME49 (type II non-virulent strains, weekly immunosuppressed with Cy and challenged with the CH3 or EGS virulent strains (I/III. Parasites recovered from surviving mice were submitted to PCR-RFLP analysis to confirm co-infection. Prime-infection with the D8 strain conferred more protection against challenge with the CH3 and EGS strains when compared with ME49 prime infection. Cy treatment caused significant leukopenia in the infected mice, what probably favors reinfection after challenge. Reinfection was associated with increased levels of IgA. Otherwise, Cy-treated mice presented significantly lower IgA levels after challenge, suggesting involvement of this immunoglobulin on protection against reinfection. In conclusion, BALB/c mice susceptibility to reinfection by T. gondii is related to genetic differences among the strains used for primary and challenge infections. Alteration of the host’s immune integrity by Cy probably compromises the protection previously established by primary infection.

  11. Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women

    DEFF Research Database (Denmark)

    Roensbo, Mette T; Blaakaer, Jan; Skov, Karin

    2018-01-01

    INTRODUCTION: Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed...... in 2014 had three cervical cytologies performed; one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas(®) HPV Test and CLART(®) HPV2 Test. RESULTS: Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high......-risk HPV was 15.0 (95% CI; 7.1-26.6) and the prevalence was higher among BMTR (29.4, CI; 10.3-56.0) than in RTR (9.3%, CI; 2.6-22.1) although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad with HPV 45 as the most common genotype (3.3%). The prevalences of high...

  12. Abnormal chest shadow on CT in immunosuppressed patients

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    Tanaka, Nobuyuki; Matsumoto, Tsuneo; Nakamura, Hiroshi

    1992-01-01

    An abnormal chest shadow was observed on CT scans in 25 cases of 23 immunosuppressed patients. Pulmonary disease was pathologically confirmed to be pneumocystis carinii pneumonia (PC pneumonia) in four patients, cytomegalovirus pneumonia (CMV pneumonia) in one, bacterial pneumonia in seven, fungal infection in three, miliary tuberculosis in one, leukemic infiltration in two, lymphangitis carcinomatosa in three, drug-induced pneumonitis in three, and ARDS in one. In almost all patients, especially those with infectious diseases such as PC pneumonia, CMV pneumonia, and bacterial pneumonia, the abnormal shadow was wide and visible in the bilateral lung fields. We presumed that such findings as lobular shadow, centrilobular shadow, and mosaic pattern reflected the extension of disease via the respiratory tract, and that those findings are typical of infectious diseases. Because such findings as abnormal linear shadow and swelling of a broncho-vascular bundle were very frequently recognized in patients with lymphangitis carcinomatosa and frequently recognized in those with drug-induced pneumonitis, these diseases may be distinguished from other diseases. An area of slightly increased density was frequently recognized in patients with PC pneumonia, bacterial pneumonia, and drug-induced pneumonitis. Such lesions were pathologically confirmed to be located in the interstitium and/or alveolus. CT was extremely useful in comprehending the character and extension of particular diseases among various diseases. As the number of patients studied was small, the utility of CT in immunosuppressed patients requires further investigation in a larger number of patients. (author)

  13. Use of multiple immunosuppressive agents in recalcitrant ACANTHAMOEBA scleritis.

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    Igras, Estera; Murphy, Conor

    2015-04-15

    A 48-year-old woman who is a contact lens wearer presented with unilateral ACANTHAMOEBA keratitis, confirmed by PCR, which responded initially to topical polyhexamethylene biguanide (PHMB) and brolene. Three months later, despite continued treatment, she developed diffuse anterior scleritis with severe pain and marked scleral injection but without evidence of recurrence keratitis. Oral non-steroidal anti-inflammatories and oral high-dose corticosteroids were added without success. Subsequent treatment with intravenous methylprednisolone and high-dose cyclosporine led to a temporary improvement. Re-presenting with signs of recurrent scleritis and severe pain, the antitumor necrosis factor monoclonal antibody adalimumab, and later oral cyclophosphamide, were added. This led to complete quiescence of the scleritis. Unfortunately, frequent recurrences of ACANTHAMOEBA keratitis and anterior uveitis occurred on immunosuppression requiring continued treatment with PHMB, brolene and topical corticosteroids. This is the first case of severe refractory ACANTHAMOEBA scleritis requiring the concomitant use of four immunosuppressive agents to achieve continued disease control. The challenges in managing this case are discussed. 2015 BMJ Publishing Group Ltd.

  14. Radiation therapy

    International Nuclear Information System (INIS)

    Bader, J.L.; Glatstein, E.

    1987-01-01

    The radiation oncologist encounters the critically ill immunosuppressed patient in four settings. First, the newly diagnosed cancer patient presents for initial evaluation and treatment, with immunosuppression from the cancer itself, malnutrition, concomitant infectious disease, prior drug or alcohol abuse or other medical problems. Second, the previously treated cancer patient presents with metastatic or recurrent primary cancer causing local symptoms. Immune dysfunction in this setting may be due to prior chemotherapy and/or radiation as well as any of the original factors. Third, the patient previously treated with radiation presents with a life-threatening problem possibly due to complications of prior therapy. In this setting, the radiation oncologist is asked to evaluate the clinical problem and to suggest whether radiation might be causing part or all of the problem and what can be done to treat these sequelae of radiation. Fourth, the patient with a benign diagnosis (not cancer) is seen with a problem potentially emeliorated by radiation (e.g., kidney transplant rejection, preparation for transplant, or intractable rheumatoid arthritis). This chapter reviews these four issues and presents clinical and radiobiologic principles on which recommendations for therapy are based

  15. Oncospheres of Taenia solium and T. saginata asiatica develop into metacestodes in normal and immunosuppressed mice.

    Science.gov (United States)

    Wang, I C; Ma, Y X; Guo, J X; Chung, W C; Lu, S C; Ito, A; Fan, P C

    1999-06-01

    Normal and immunosuppressed mice were infected with oncospheres of Taenia saginata asiatica and T. solium. Although normal ICR mice were not susceptible to these two parasites, cysticerci were recovered from the immunosuppressed ones following venous injection. For T. s. asiatica, immunosuppressed ICR mice had an infection rate of 12.5% and six cysticerci of this parasite were recovered from three males. After injection of T. solium oncospheres, a high infection rate of 57% was obtained and 23 cysticerci were collected from 13 male immunosuppressed ICR mice. The immunosuppressed C57 mice had the highest infection rate (100%) and cysticercus recovery rate (2.4%) for T. solium. The infection rate and cysticercus recovery rate in six normal C57 mice were 40% and 3% respectively. The immunosuppressed ICR, Balb/c and C3H mice were also susceptible to T. s. asiatica.

  16. African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

    Science.gov (United States)

    Malat, Gregory E; Culkin, Christine; Palya, Aniruddha; Ranganna, Karthik; Kumar, Mysore S Anil

    2009-10-22

    Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors

  17. Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

    Science.gov (United States)

    Castro-Manrreza, Marta E.; Mayani, Hector; Monroy-García, Alberto; Flores-Figueroa, Eugenia; Chávez-Rueda, Karina; Legorreta-Haquet, Victoria; Santiago-Osorio, Edelmiro

    2014-01-01

    Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM—the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BM-MSCs and UCB-MSCs significantly inhibited the proliferation of both CD4+ and CD8+ activated T cells in a cell–cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-γ, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4+CD25+CTLA-4+. Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications. PMID:24428376

  18. Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

    Science.gov (United States)

    Tanaka, Seiji; Saikusa, Tomoko; Katafuchi, Yuno; Ushijima, Kosuke; Ohtsu, Yasushi; Tsumura, Naoki; Ito, Yuhei

    2015-09-11

    A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol.

    Science.gov (United States)

    Hibino, Satoshi; Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Iwata, Naoyuki; Ito, Hidekazu; Nakano, Masaru; Tanaka, Kazuki

    2015-01-01

    This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome. Cyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high-dose steroid therapy. CsA was maintained at an area under the whole blood concentration-time curve up to 4 h after dose (AUC0-4 ) of 1500 and 2000 ng·h/mL in steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. Ninety-one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission. In the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid-sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped. Treatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS. © 2014 Japan Pediatric Society.

  20. Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance

    Science.gov (United States)

    Zhang, Song; MacConmara, Malcolm; Gao, Ang; Sandikci, Burhaneddin; Ayvaci, Mehmet U. S.; Mete, Mutlu; Tsapepas, Demetra; Rajora, Nilum; Mohan, Prince; Lakhia, Ronak; Lu, Christopher Y.; Vazquez, Miguel

    2015-01-01

    Background and objectives Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. Design, setting, participants, & measurements The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Results Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. Conclusions Compared

  1. Colonization and infection with Trichosporon species in the immunosuppressed host.

    Science.gov (United States)

    Haupt, H M; Merz, W G; Beschorner, W E; Vaughan, W P; Saral, R

    1983-02-01

    Trichosporon beigelii and Trichosporon capitatum have recently been recognized as systemic pathogens in the immunosuppressed host. We studied the incidence of colonization and systemic infection with these organisms in 353 highly immunocompromised patients over a 37-month period. Thirteen patients (3.7%) had positive surveillance cultures for Trichosporon species in stool, skin, or urine. Three of the 13 patients developed systemic infections after having positive surveillance cultures. In two of these three patients, urine cultures were positive near the time of systemic infection. The route of entry appeared to have been enteric in two patients and cutaneous in one patient. Both colonizing and infecting organisms showed in vitro susceptibility to amphotericin B and nystatin. This study suggests that positive surveillance cultures for Trichosporon species may correlate with systemic infection in the severely immunocompromised patient and that repeated positive urine cultures may indicate dissemination.

  2. Critical appraisal on the use of everolimus in renal transplantation as an immunosuppressant to prevent organ transplant rejection

    Directory of Open Access Journals (Sweden)

    Fernando Giron

    2010-01-01

    Full Text Available Fernando Giron, Yenny BaezKidney Transplant Service, Colombiana de Trasplantes, Bogota, ColombiaAbstract: Everolimus is a proliferation inhibitor designed to target chronic allograft nephropathy including prevention of acute rejection. Acute renal allograft rejection incidence varies with the therapy used for immunosuppression. Registry data show that 15% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Everolimus has been used as therapy with full- or reduced-dose cyclosporine A without evidence of increasing the acute rejection incidence. This review will summarize the available clinical trial data on the use of everolimus and its role in preventing acute rejection incidence in renal transplantation.Keywords: calcineurin inhibitors, cyclosporine, everolimus, biopsy-proven acute rejection, renal transplantation, acute rejection

  3. Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform.

    Science.gov (United States)

    Zarrinpar, Ali; Lee, Dong-Keun; Silva, Aleidy; Datta, Nakul; Kee, Theodore; Eriksen, Calvin; Weigle, Keri; Agopian, Vatche; Kaldas, Fady; Farmer, Douglas; Wang, Sean E; Busuttil, Ronald; Ho, Chih-Ming; Ho, Dean

    2016-04-06

    Posttransplant immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges. Inter- and intraindividual variability in dosing requirements conventionally use physician-guided titrated drug administration, which results in frequent deviations from the target trough ranges, particularly during the critical postoperative phase. There is a clear need for personalized management of posttransplant regimens to prevent adverse events and allow the patient to be discharged sooner. We have developed the parabolic personalized dosing (PPD) platform, which is a surface represented by a second-order algebraic equation with experimentally determined coefficients of the equation being unique to each patient. PPD uses clinical data, including blood concentrations of tacrolimus--the primary phenotypic readout for immunosuppression efficacy--to calibrate these coefficients and pinpoint the optimal doses that result in the desired patient-specific response. In this pilot randomized controlled trial, we compared four transplant patients prospectively treated with tacrolimus using PPD with four control patients treated according to the standard of care (physician guidance). Using phenotype to personalize tacrolimus dosing, PPD effectively managed patients by keeping tacrolimus blood trough levels within the target ranges. In a retrospective analysis of the control patients, PPD-optimized prednisone and tacrolimus dosing improved tacrolimus trough-level management and minimized the need to recalibrate dosing after regimen changes. PPD is independent of disease mechanism and is agnostic of indication and could therefore apply beyond transplant medicine to dosing for cancer, infectious diseases, and cardiovascular medicine, where patient response is variable and requires careful adjustments through optimized inputs. Copyright © 2016, American Association for the Advancement of Science.

  4. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    Science.gov (United States)

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  5. Study of immunosuppressive factor (ISF) and immunosuppressive acidic protein (IAP) levels in 23 patients with uterus or esophageal cancer on radiotherapy

    International Nuclear Information System (INIS)

    Seno, Masao; Tsuru, Sumiaki; Kitani, Hideo; Zinnaka, Yutaka.

    1984-01-01

    Immunosuppressive factor (ISF) and immunosuppressive acidic protein (IAP) levels in 23 patients with uterus or esophageal cancer were assayed before and after radiotherapy. The results were as follows: (1) Serum ISF level increased while serum IAP level decreased with progress of radiotherapy. A negative correlation between ISF and IAP was found. (2) Administration of RSK (Krestin) for patients after radiotherapy was found to be effective in the follow-up examination of serum ISF level. (author)

  6. Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

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    Lee, Won-Jae [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Hah, Young-Sool [Biomedical Research Institute, Gyeongsang National University Hospital, Jinju (Korea, Republic of); Ock, Sun-A. [Animal Biotechnology Division, National Institute of Animal Science, RDA, Suwon 441-706, Gyeonggi (Korea, Republic of); Lee, Jae-Hoon; Jeon, Ryong-Hoon; Park, Ji-Sung [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sang-Il [Department of Internal Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju (Korea, Republic of); Rho, Na-Young [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 4S7 (Canada); Rho, Gyu-Jin [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sung-Lim, E-mail: sllee@gnu.ac.kr [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of)

    2015-05-01

    The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice. - Highlights: • Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. • Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. • SF-MSCs exhibited improved therapeutic effects than BM-MSCs. • SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases.

  7. The Immunosuppressant Effect Comparation Between Ethyl Acetate and n-Butanol Fractions of Kalanchoe Pinnata (Lmk Pers In 2,6,10,14 Tetramethylpentadecane-Treated Mice

    Directory of Open Access Journals (Sweden)

    Niken Indriyanti

    2017-07-01

    Full Text Available Immunosuppressant drugs are the main treatment of lupus patient. The ACR and SLICC treatment guidelines are able to increase the quality of life, but the outcome is not satisfying since the off-label therapy of corticosteroids and cytotoxic drugs give a lot of side effects. Many breakthrough efforts still develop in order to find the safe and effective drugs for lupus, such as finding immunosuppressant drugs from natural resources. One of the potential resources is Kalanchoe pinnata (Lmk Pers, which have immunosuppressant, anti-inflammatory, antinociceptive, and antioxidant effects. Thus, in the previous study, we found the effect of the aqueous extract of Kalanchoe pinnata (Lmk Pers is active to repair the lupus manifestation in 2,6,10,14 tetramethylpentadecane (TMPD-treated mice. Then, this research was focused on the in vivo immunosuppressant effect of a flavonoid-rich fraction of the extract which was consisted of the ethyl acetate (FE and n-butanol (FB fractions. The induction method and the extraction procedure were the same as the previous study and then the fractionation was performed by using liquid-liquid extraction. After 2-week treatment of both fractions, we obtained the differences in the total leukocytes, organ indexes, and also the spleen, kidney, and joint structure parameters. The total leukocyte of the FE group was 3,600±264 cells/mm3, which was lower than that in the FB group. The spleen and kidney indexes increased after the administration of FB fraction, while the FE fraction was not. At last, despite the histology observation of spleen resembled mild structural changes differences, the clear differences between both treatment groups occurred in the kidney and joint histology. The differences led to a conclusion that the FE fraction has the better immunosuppressant effect in TMPD-treated mice.

  8. Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single-center experience.

    Science.gov (United States)

    Kim, J; Patnaik, N; Chorny, N; Frank, R; Infante, L; Sethna, C

    2014-01-01

    Most cases of idiopathic nephrotic syndrome in childhood are responsive to corticosteroids. However, there is a small group of children that demonstrate steroid resistance (steroid-resistant nephrotic syndrome; SRNS), steroid dependence, or that frequently relapse (frequent-relapse steroid-sensitive nephrotic syndrome; FR-SSNS) which are more clinically difficult to treat. Therefore, second-line immunosuppressants, such as alkylating agents, calcineurin inhibitors, antimetabolites and, more recently, rituximab, have been used with varying success. The objective was to evaluate the response rates of various second-line therapies in the treatment of childhood nephrotic syndrome. A retrospective chart review of pediatric subjects with idiopathic nephrotic syndrome was conducted at a single tertiary care center (2007-2012). Drug responses were classified as complete response, partial response, and no response. Of the 188 charts reviewed, 121 children were classified as SSNS and 67 children as SRNS; 58% were classified as FR-SSNS. Sixty-five subjects were diagnosed with focal segmental glomerulosclerosis via biopsy. Follow-up ranged from 6 months to 21 years. The combined rate of complete and partial response for mycophenolate mofetil (MMF) was 65% (33/51) in SSNS and 67% (6/9) in SRNS. For tacrolimus, the response rate was 96% (22/23) for SSNS and 77% (17/22) for SRNS. Eighty-three percent (5/6) of SSNS subjects treated with rituximab went into complete remission; 60% relapsed after B-cell repletion. Eight refractory subjects were treated with combined MMF/tacrolimus/corticosteroid therapy with a 75% response rate. Our experience demonstrates that older medications can be replaced with newer ones such as MMF, tacrolimus, and rituximab with good outcomes and better side effect profiles. The treatment of refractory cases with combination therapy is promising.

  9. Second-Line Immunosuppressive Treatment of Childhood Nephrotic Syndrome: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    J. Kim

    2014-01-01

    Full Text Available Objective: Most cases of idiopathic nephrotic syndrome in childhood are responsive to corticosteroids. However, there is a small group of children that demonstrate steroid resistance (steroid-resistant nephrotic syndrome; SRNS, steroid dependence, or that frequently relapse (frequent-relapse steroid-sensitive nephrotic syndrome; FR-SSNS which are more clinically difficult to treat. Therefore, second-line immunosuppressants, such as alkylating agents, calcineurin inhibitors, antimetabolites and, more recently, rituximab, have been used with varying success. The objective was to evaluate the response rates of various second-line therapies in the treatment of childhood nephrotic syndrome. Study Design: A retrospective chart review of pediatric subjects with idiopathic nephrotic syndrome was conducted at a single tertiary care center (2007-2012. Drug responses were classified as complete response, partial response, and no response. Results: Of the 188 charts reviewed, 121 children were classified as SSNS and 67 children as SRNS; 58% were classified as FR-SSNS. Sixty-five subjects were diagnosed with focal segmental glomerulosclerosis via biopsy. Follow-up ranged from 6 months to 21 years. The combined rate of complete and partial response for mycophenolate mofetil (MMF was 65% (33/51 in SSNS and 67% (6/9 in SRNS. For tacrolimus, the response rate was 96% (22/23 for SSNS and 77% (17/22 for SRNS. Eighty-three percent (5/6 of SSNS subjects treated with rituximab went into complete remission; 60% relapsed after B-cell repletion. Eight refractory subjects were treated with combined MMF/tacrolimus/corticosteroid therapy with a 75% response rate. Conclusion: Our experience demonstrates that older medications can be replaced with newer ones such as MMF, tacrolimus, and rituximab with good outcomes and better side effect profiles. The treatment of refractory cases with combination therapy is promising.

  10. Rationale and effect of reduction of immunosuppressive load in organ transplant recipients

    NARCIS (Netherlands)

    J. van de Wetering (Jacqueline)

    2011-01-01

    textabstractGiving a patient immunosuppressive medication is creating an environment in which a transplanted organ will be accepted and rejection will be prevented. Unfortunately, the use of immunosuppression is complicated by serious side effects. After dealing with acute rejection in solid organ

  11. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders.

    Science.gov (United States)

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-11-15

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system's ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.

  12. Immunosuppression for acquired hemophilia A : results from the European Acquired Haemophilia Registry (EACH2)

    NARCIS (Netherlands)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Levesque, Herve; Nemes, Laszlo; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kuehne, Angela; Aspoeck, Gerold; Heistinger, Max; Knobl, Paul; Makipernaa, Anne; Andre, Helene; Aouba, A; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; dOiron, Roseline; Gautier, Philippe; Gay, Valerie; Girault, Stephane; Gruel, Yves; Guerin, Viviane; Hezard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Levesque, Herve; Lifermann, Francois; Marlu, Raphael; Ninet, J.; Peynet, Jocelyne; Quemeneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sebastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Huth-Kuhne, Angela; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Nemes, Laszlo; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Baudo, Francesco; Caimi, T.; Contino, L.; D'Angelo, Armando; Crippa, Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Matteo Nicola Dario; D'inca, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; De Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyak, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W.G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P.W.G; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; Del Campo, Raquel; Ferreiro Arguelles, M.; Gonzalez Boullosa, Rosario; Gutierrez Pimentel, Maria Jose; Jimenez-Yuste, Victor [No Value; Jose-Felix, Lucia; Marco, Pascual; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia z; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana Maria; Maranon, HGUG [No Value; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Tengborn, Lilian; Boehlen, Francoise; Korte, Wolfgang; Chowdary, Pratima; Collins, Peter; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan

    2012-01-01

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive

  13. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

    NARCIS (Netherlands)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela; Aspoeck, Gerold; Heistinger, Max; Knöbl, Paul; Makipernaa, Anne; André, Hélène; Aouba, Achille; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; d'Oiron, Roseline; Gautier, Philippe; Gay, Valérie; Girault, Stéphane; Gruel, Yves; Guerin, Viviane; Hézard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Lifermann, François; Marlu, Raphael; Ninet, Jacques; Peynet, Jocelyne; Quéméneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sébastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Caimi, Teresa; Contino, Laura; D'Angelo Armando, Crippa Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Dario; D'incà, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; de Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyák, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W. G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P. W. G.; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; del Campo, Raquel; Ferreiro Argüelles, María; González Boullosa, Rosario; Gutiérrez Pimentel, María José; Jiménez-Yuste, Victor; Jose-Felix, Lucia; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia Z.; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana María; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Boehlen, Françoise; Korte, Wolfgang; Chowdary, Pratima; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan

    2012-01-01

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive

  14. Pulmonary tuberculosis in a patient with rheumatoid arthritis undergoig immunosuppressive treatment: case report

    Directory of Open Access Journals (Sweden)

    Sandro Ceratti

    2014-02-01

    Full Text Available Rheumatoid arthritis is a disease which characteristically affects the joints. Because it is an autoimmune disease, immunosuppressive drugs are widely used in its treatment. The present case report illustrates the association of immunosuppressive treatment with the development of opportunistic infections in a 64-year-old patient.

  15. Renal transplant patients' preference for the supply and delivery of immunosuppressants in Wales: a discrete choice experiment.

    Science.gov (United States)

    Hagemi, Anke; Plumpton, Catrin; Hughes, Dyfrig A

    2017-10-02

    Prescribing policy recommendations aimed at moving immunosuppressant prescribing for renal transplant patients from primary to secondary care may result in benefits of increased safety and reduced cost. However, there is little evidence of patients' preferences for receiving their immunosuppressant therapy from hospitals compared to community dispensing. The aim of this study was to elicit patient preferences for different service configurations focusing in particular on home delivery versus collection of medication from hospital. A discrete choice experiment was administered to 265 renal transplant patients in North Wales. Respondents were presented 18 pairwise choices, labelled as either home delivery or hospital collection, and described by the attributes: frequency of supply, waiting time (for delivery or collection) and method of ordering (provider contact, patient contact via phone, patient contact electronically). Data were analysed using a random-effects logit model and marginal rates of substitution calculated based on the waiting time attribute. A response rate of 63% was achieved, with 5332 usable observations from 150 respondents. Method of delivery (β coefficient 1.21; 95% confidence interval 1.05 to 1.38), frequency of supply (0.05; 0.03 to 0.08) waiting time (-0.00, -0.00 to -0.00), provider contact (desirable) (0.20; 0.12 to 0.27), patient contact by telephone (desirable) (0.09; 0.01 to 0.17) and patient contact electronically (undesirable) (-0.292; -0.37 to -0.21) were statistically significant (p delivery service. Patients indicate a clear preference for a home delivery service. They prefer providers to make contact when new immunosuppressant supplies are required and show preference against ordering medication electronically. A policy for secondary care prescribing and hospital collection of medicines does not align with this preference.

  16. Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

    Science.gov (United States)

    Cuq, B; Blois, S L; Mathews, K A

    2017-06-01

    To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

  17. Metallodrugs in targeted cancer therapeutics. Aiming at chemoresistance-related patterns and immunosuppressive tumor networks

    Science.gov (United States)

    Salifoglou, Athanasios; Petanidis, Savvas; Kioseoglou, Efrosini

    2017-11-16

    Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer agents yet they exhibit undesirable side-effects and are effective against only a few types of cancers. A need, therefore, arises for new metallodrugs with an improved spectrum of efficacy and lower toxicity. Development of anticancer drugs based on antitumor metals is currently a very active field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate structural modification. In that respect, comprehending the molecular factors involved in drug resistance and immune response may help us develop new strategies toward more promising chemotherapies, reducing the rate of relapse and overcoming chemoresistance. In this review, a) molecular immune-related mechanisms in the tumor microenvironment, leading to decreased drug sensitivity, along with b) strategies for reversing drug resistance and targeting immunosuppressive tumor networks, while concurrently optimizing the design of complex metalloforms bearing anti-tumor activity, are discussed in an effort to identify and overcome underlying mechanisms of chemoresistance to both standard chemotherapeutic agents and targeted molecular therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    Science.gov (United States)

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  19. Immunosuppressive Effects of the Traditional Chinese Herb Qu Mai on Human Alloreactive T Cells

    Science.gov (United States)

    Reid-Adam, Jessica; Yang, Nan; Song, Ying; Cravedi, Paolo; Li, Xiu-Min; Heeger, Peter

    2013-01-01

    Current therapies for transplant rejection are sub-optimally effective. In an effort to discover novel immunosuppressants we used cytokine ELISPOT and ELISAs to screen extracts from 53 traditional Chinese herbs for their ability to suppress human alloreactive T cells. We identified a dichloromethane-soluble fraction (QMAD) of Qu Mai (Dianthus superbus) as a candidate. HPLC analysis of QMAD revealed 3 dominant peaks, each with a MW ~600 Daltons and distinct from cyclosporine and rapamycin. When we added QMAD to human mixed lymphocyte cultures, we observed dose-dependent inhibition of proliferation and IFNγ production, by naïve and memory alloreactive T cells, and observed an increased frequency of Foxp3+CD4+ T cells. To address whether QMAD induces regulatory T cells we added QMAD to anti-CD3/CD28-stimulated naïve CD4 T cells and observed a dose-dependent upregulation of Foxp3 associated with new suppressive capacity. Mechanistically, QMAD did not induce T cell IL-10 or TGFβ but blocked T cell AKT phosphorylation, a key signaling nexus required for T cell proliferation and expansion, that simultaneously prevents Foxp3 transcription. Our findings provide novel insight into the anti-inflammatory effects of one traditional Chinese herb, and support the need for continued isolation, characterization and testing of QMAD-derived components as immune suppressants for transplant rejection. PMID:23433080

  20. Prototheca zopfii associated diverticulitis in an immunosuppressed host, a case presentation and literature review

    Directory of Open Access Journals (Sweden)

    Kyle W. Meinke

    2017-11-01

    Full Text Available Clinical infection with Prototheca species can present in many ways including cutaneous, bursal, or disseminated forms. Of these clinical forms, protothecal intestinal infections are a very rare occurrence, and there have only been a few documented cases within the medical literature. We present a case of a 67 year old African American male who presented to our veterans hospital with bowel obstruction. The patient has a pertinent medical history of prolonged immunosuppressive therapy for cadaveric renal transplant, Clostridium difficile infection, herpetic perirectal ulcer, and diverticulosis. The patient presented with symptoms of weight loss, left lower quadrant pain, and pencil thin stool. Colonoscopic and barium studies confirmed a complete obstruction at the level of the distal descending colon. Carcinoembryonic levels were within normal limits. The patient underwent a left hemicolectomy, and gross examination of the specimen revealed a markedly thickened bowel wall with multiple diverticula. Histologic examination revealed diverticular disease with associated transmural inflammation and numerous associated dark round structures. The basophilic round structures appeared to contain cell walls and stained positively for fungal stains. Overall, the diagnosis of Prototheca zopfii was made based on the characteristic histopathologic features and the results of the fungal staining pattern. To our knowledge, this is the first reported case of a colonic diverticulitis with involvement by Prototheca zopfii. We present an overview of the biology, epidemiology, histopathologic features, clinical manifestations, and treatment options of Prototheca as it relates to our patient.

  1. Miliary tuberculosis occurred after immunosuppressive drug in PNH patient with completely cured tuberculosis; a case report

    Science.gov (United States)

    2012-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder that presents with hemolytic anemia, marrow failure and thrombophilia. During acute attacks, corticosteroid can alleviate the hemolytic paroxysm, but the prolonged administration induces serious toxicity including immunosuppression. So American thoracic society (ATS) for tuberculosis (TB) recommends prophylactic anti-TB medication in patients with a long-term steroid therapy. However, in the patient who was treated for active TB in the past, there are no guidelines of the test for determining patients who have latent TB infection (LTBI) and no recommendations of TB prophylaxis if there is no evidence of reactivation at present. A 40-year-old male patient presented with fever and aggravated weakness for a week. He was diagnosed with PNH a month ago and took corticosteroid for 3 weeks. In the past, he was diagnosed with pulmonary TB and completely cured after treatment. According to guideline, he was not indicated with TB prophylaxis. However, he caught miliary TB, progressed to acute respiratory distress syndrome. We experience this embarrassing case, and emphasize the need to investigate multicentral TB prevalence and to make the guidelines of anti-TB medication in subgroups of hematologic diseases including PNH. PMID:22554314

  2. Miliary tuberculosis occurred after immunosuppressive drug in PNH patient with completely cured tuberculosis; a case report

    Directory of Open Access Journals (Sweden)

    Lee Jihyun

    2012-05-01

    Full Text Available Abstract Paroxysmal nocturnal hemoglobinuria (PNH is a clonal disorder that presents with hemolytic anemia, marrow failure and thrombophilia. During acute attacks, corticosteroid can alleviate the hemolytic paroxysm, but the prolonged administration induces serious toxicity including immunosuppression. So American thoracic society (ATS for tuberculosis (TB recommends prophylactic anti-TB medication in patients with a long-term steroid therapy. However, in the patient who was treated for active TB in the past, there are no guidelines of the test for determining patients who have latent TB infection (LTBI and no recommendations of TB prophylaxis if there is no evidence of reactivation at present. A 40-year-old male patient presented with fever and aggravated weakness for a week. He was diagnosed with PNH a month ago and took corticosteroid for 3 weeks. In the past, he was diagnosed with pulmonary TB and completely cured after treatment. According to guideline, he was not indicated with TB prophylaxis. However, he caught miliary TB, progressed to acute respiratory distress syndrome. We experience this embarrassing case, and emphasize the need to investigate multicentral TB prevalence and to make the guidelines of anti-TB medication in subgroups of hematologic diseases including PNH.

  3. Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

    Science.gov (United States)

    Ye, Wen-Ling; Tang, Nan; Wen, Yu-Bing; Li, Hang; Li, Min-Xi; Du, Bin; Li, Xue-Mei

    2016-11-01

    Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) renal function to baseline values. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

  4. First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs.

    Science.gov (United States)

    Fiocchi, R; D'Elia, E; Vittori, C; Sebastiani, R; Strobelt, N; Eleftheriou, G; Introna, M; Freddi, C; Crippa, A

    2016-04-01

    The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats

    Directory of Open Access Journals (Sweden)

    Kabat-Koperska J

    2016-07-01

    Full Text Available Joanna Kabat-Koperska,1 Agnieszka Kolasa-Wołosiuk,2 Bartosz Wojciuk,3 Iwona Wojciechowska-Koszko,3 Paulina Roszkowska,3 Barbara Krasnodębska-Szponder,3 Edyta Paczkowska,4 Krzysztof Safranow,5 Edyta Gołembiewska,1 Bogusław Machaliński,4 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology and Internal Medicine, 2Department of Histology and Embryology, 3Department of Microbiology and Immunological Diagnostics, 4Department of General Pathology, 5Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland Background: In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system – the thymus and the spleen. Methods: The study was conducted on 40 (32+8 female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results: There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17 after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Conclusion: Qualitative, quantitative, and morphological changes in the immune system of infant

  6. Immunosuppressive activity of florfenicol on the immune responses in mice.

    Science.gov (United States)

    Shuang, Guan; Yu, Song; Weixiao, Guo; Dacheng, Wang; Zhichao, Zhang; Jing, Lu; Xuming, Deng

    2011-01-01

    Florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, florfenicol suppressed lipopolysaccharide (LPS)-stimulated splenocyte proliferation in a concentration-dependent manner in vitro and in vivo. BALB/c mice were immunized subcutaneously with OVA on days 1 and 4. Following the second immunization, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200 mg/kg) for 10 consecutive days. On day 14, blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies, and splenocytes were harvested to assess lymphocyte proliferation, CD3(+) T and CD19(+) B lymphocyte subsets. The results presented here demonstrate that florfenicol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation but also decreased the percentage of CD19(+) B cells in a dose-dependent manner and suppressed CD3(+) T cell at high doses. Moreover, OVA-specific IgG, IgG1 and IgG2b titers in OVA-immunized mice were reduced by florfenicol. These results suggest that florfenicol could suppress humoral and cellular immune responses in mice.

  7. Low Adherence to Immunosuppressants Is Associated With Symptom Experience Among Kidney Transplant Recipients.

    Science.gov (United States)

    Lee, S Y; Chu, S H; Oh, E G; Huh, K H

    2015-11-01

    The purpose of this study was to investigate the relationship between immunosuppressant-related symptom experience (SE) and adherence to immunosuppressant regimens among kidney transplant (KT) recipients. A total of 239 KT recipients on an immunosuppressant regimen who were followed up after transplantation participated in this study. Data was collected through a self-reported questionnaire survey (medication adherence, SE, and quality of life) and medical record review. Low adherence in the immunosuppressant group was associated with longer time since KT, less comorbidity (adherence among KT recipients showed significantly greater overall symptom occurrence (P = .001) and symptom distress (P = .002) levels than patients with high or medium adherence after adjusting for a number of covariates. The most common symptom both in terms of occurrence (96.4%) and distress (91.1%) among poorly adherent KT recipients was tiredness. Low adherence to an immunosuppressant regimen was significantly associated with high SE among KT recipients. Strategies to decrease immunosuppressant-related SE are needed to improve adherence to immunosuppressants. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Immunopathological changes in the brain of immunosuppressed mice experimentally infected with Toxocara canis.

    Science.gov (United States)

    Eid, Mohamed M; El-Kowrany, Samy I; Othman, Ahmad A; El Gendy, Dina I; Saied, Eman M

    2015-02-01

    Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.

  9. Immunosuppression in irradiated breast cancer patients: In vitro effect of cyclooxygenase inhibitors

    International Nuclear Information System (INIS)

    Wasserman, J.; Blomgren, H.; Rotstein, S.; Petrini, B.; Hammarstroem, S.

    1989-01-01

    We have documented in previous studies that local irradiation therapy for breast cancer caused severe lymphopenia with reduction of both T and non-T lymphocytes. Non-T cells were relatively more depressed but recovered within six months. The recovery of T cells, on the other hand, remained incomplete 10-11 years after irradiation. Several lymphocyte functions were also severely impaired. An association was found between prognosis and postirradiation mitogen reactivity of lymphocytes from these patients. Mortality up to eight years after irradiation was significantly higher in patients with low postirradiation phytohemagglutinin and PPD reactivity. The radiation induced decrease in mitogenic response seemed mainly to be caused by immunosuppressive monocytes, which suggests that the underlying mechanism might be mediated by increased production of prostaglandins by monocytes. For this reason we examined the effect of some cyclooxygenase products on different lymphocyte functions and found that prostaglandins A2, D2, and E2 inhibited phytohemagglutinin response in vitro. Natural killer cell activity was also reduced by prostaglandins D2 and E2. The next step was to examine various inhibitors of cyclooxygenase in respect to their capacity to revert irradiation-induced suppression of in vitro mitogen response in lymphocytes from breast cancer patients. It was demonstrated that Diclofenac Na (Voltaren), Meclofenamic acid, Indomethacin, and lysin-mono-acetylsalicylate (Aspisol) could enhance mitogen responses both before and after radiation therapy. This effect was most pronounced at completion of irradiation. On a molar basis, Diclofenac Na was most effective followed by Indomethacin, Meclofenamic acid, and lysin-monoacetylsalicylate

  10. Immunosuppression in irradiated breast cancer patients: In vitro effect of cyclooxygenase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Wasserman, J.; Blomgren, H.; Rotstein, S.; Petrini, B.; Hammarstroem, S.

    1989-01-01

    We have documented in previous studies that local irradiation therapy for breast cancer caused severe lymphopenia with reduction of both T and non-T lymphocytes. Non-T cells were relatively more depressed but recovered within six months. The recovery of T cells, on the other hand, remained incomplete 10-11 years after irradiation. Several lymphocyte functions were also severely impaired. An association was found between prognosis and postirradiation mitogen reactivity of lymphocytes from these patients. Mortality up to eight years after irradiation was significantly higher in patients with low postirradiation phytohemagglutinin and PPD reactivity. The radiation induced decrease in mitogenic response seemed mainly to be caused by immunosuppressive monocytes, which suggests that the underlying mechanism might be mediated by increased production of prostaglandins by monocytes. For this reason we examined the effect of some cyclooxygenase products on different lymphocyte functions and found that prostaglandins A2, D2, and E2 inhibited phytohemagglutinin response in vitro. Natural killer cell activity was also reduced by prostaglandins D2 and E2. The next step was to examine various inhibitors of cyclooxygenase in respect to their capacity to revert irradiation-induced suppression of in vitro mitogen response in lymphocytes from breast cancer patients. It was demonstrated that Diclofenac Na (Voltaren), Meclofenamic acid, Indomethacin, and lysin-mono-acetylsalicylate (Aspisol) could enhance mitogen responses both before and after radiation therapy. This effect was most pronounced at completion of irradiation. On a molar basis, Diclofenac Na was most effective followed by Indomethacin, Meclofenamic acid, and lysin-monoacetylsalicylate.

  11. Successful reduction of immunosuppression in older renal transplant recipients who exhibit donor-specific regulation

    Science.gov (United States)

    Jankowska-Gan, E.; Sollinger, H. W.; Pirsch, J. D.; Cai, J.; Pascual, J.; Haynes, L. D.; Munoz del Rio, A.; Burlingham, W. J.

    2009-01-01

    Background We hypothesized that T regulatory cells (TR) specific for donor alloantigens would protect a renal transplant during partial withdrawal of immunosuppression (IS). Methods To test this hypothesis, 32 renal transplant recipients >55 years old with excellent renal function were tested for donor-specific regulation (DSR) by trans-vivo delayed type hypersensitivity (TV-DTH) assay at time of enrollment (T=0) and 6 months later (T=6). Twenty-two patients had prednisone withdrawn over a 3 month period, while 10 controls were maintained on triple therapy (prednisone, cyclosporin, mycophenolate). Results Out of 22 patients in the steroid withdrawal group, 10 were DSR+, and 12 were DSR- at the time of enrollment (T=0). None of the DSR+ patient experienced acute rejection, nor did any have donor-specific HLA antibody (DSA) during or after withdrawal. Out of 12 DSR- patients, 3 developed acute rejection, which were reversed with bolus steroid treatment, and 4 were DSA + at T=0 or T=6. Two years later, 80% (8/10) of DSR+ patients in the withdrawal group remain steroid free while maintaining excellent renal function, as compared with only 58% (7/12) DSR- patients. Patient survival at 4 years was similar for DSR+ (9/10) and DSR- (11/12) patients in the withdrawal group. Patients maintained on triple therapy remained rejection-free during the 4 yr follow up regardless of initial DSR status, with patient survival rate of 70% (7/10). Conclusions DSR prior to steroid withdrawal may identify a subset of transplant patients who could benefit from IS reduction without elevated risk of rejection, or deteriorating renal function. PMID:19696637

  12. Immunosuppressive mechanisms in cancer: consequences for the development of therapeutic vaccines.

    Science.gov (United States)

    Gross, Stefanie; Geldmacher, Astrid; Sharav, Tumenjargal; Losch, Florian; Walden, Peter

    2009-05-26

    Recent investigations revealed strong immunosuppressive mechanisms in tumors that may block anti-tumor T cells and be responsible for failures of immunotherapies. Current attempts to overcome this immunosuppression include blockade of co-inhibitory factors on T cells. Reports from the respective trials indicate that the strategy can improve efficacy of therapeutic vaccination, but at the cost of severe inflammatory and autoimmune reactions. We tried to circumvent tumor-associated immunosuppression by mimotope vaccination to broaden reactive anti-tumor T cell repertoires to include T cells that have not been rendered anergic by the tumor. Initial clinical observations suggest that this strategy bears considerable promise.

  13. [Evaluation of immunosuppressive treatment on homocystein levels in patients after kidney transplantation during a 2 year observation period].

    Science.gov (United States)

    Aksamit, Dariusz; Janda, Katarzyna; Kuźniewski, Marek; Krzanowski, Marcin; Ignacak, Ewa; Betkowska-Prokop, Alina; Chowaniec, Eve; Sułowicz, Wladysław

    2012-01-01

    months after) did not differ significantly when compared to pts receiving immunosuppressive therapy CsA vs. Tac (p=0.18). Even though notable differences were observed in the drop in Hcy level (immunosuppressive treatment scheme CsA vs. Tac) in measurements before Ktx and 24 months post (respectively: 27% and 57.6%), no statistical significance was noted (p=0.13). Using the Mann-Whitneys' Test, no statistical significance was noted (p=0.13) when comparing differences in creatinine clearance between the group of pts receiving CsA and Tac 24 months after Ktx. Patients treated with Tac achieved a higher creatinine clearance by 16.5% when compared with those receiving CsA. No significant differences were observed between these two groups (p=0.65) when serum creatinine levels were evaluated. Incidence of DGF, as well as prescribed immunosuppressive therapy does not have an influence on remote Hey levels in pts after Ktx. Graft function seems to be the main predictor that influences Hcy levels after Ktx in this group of pts.

  14. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

    Science.gov (United States)

    Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

    2018-04-07

    Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Pharmacodynamic Monitoring of Tacrolimus-based Immunosuppression in CD14+ Monocytes after Kidney Transplantation

    NARCIS (Netherlands)

    N.M. Kannegieter (Nynke); D.A. Hesselink (Dennis); M. Dieterich (Marjolein); G.N. de Graav (Gretchen); R. Kraaijeveld (Rens); A.T. Rowshani (Ajda); P.J. Leenen (Pieter); C.C. Baan (Carla)

    2017-01-01

    markdownabstractBackground: Monocytes significantly contribute to ischemia-reperfusion injury and allograft rejection after kidney transplantation. However, the knowledge about the effects of immunosuppressive drugs on monocyte activation is limited. Conventional pharmacokinetic methods for

  16. Classifying PML risk with disease modifying therapies.

    Science.gov (United States)

    Berger, Joseph R

    2017-02-01

    To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk. A method of contextualizing PML risk for DMTs is warranted. Classification of PML risk was predicated on three criteria:: 1) whether the underlying condition being treated predisposes to PML in the absence of the drug; 2) the latency from initiation of the drug to the development of PML; and 3) the frequency with which PML is observed. Among the DMTs, natalizumab occupies a place of its own with respect to PML risk. Significantly lesser degrees of risk exist for fingolimod and dimethyl fumarate. Whether PML will be observed with other DMTs in use for MS, such as, rituximab, teriflunomide, and alemtuzumab, remains uncertain. A logical classification for stratifying DMT PML risk is important for both the physician and patient in contextualizing risk/benefit ratios. As additional experience accumulates regarding PML and the DMTs, this early effort will undoubtedly require revisiting. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Infectivity of Cryptosporidium hominis and Cryptosporidium parvum Genotype 2 Isolates in Immunosuppressed Mongolian Gerbils

    OpenAIRE

    Baishanbo, Asiya; Gargala, Gilles; Delaunay, Agnès; François, Arnaud; Ballet, Jean-Jacques; Favennec, Loïc

    2005-01-01

    One-month-old dexamethasone-immunosuppressed Mongolian gerbils were challenged with 1 oocyst to 2 × 105 oocysts from two isolates genotyped as Cryptosporidium hominis and C. parvum (genotype 2), respectively. A similar dose-dependent gut infection was obtained, and the initial genotype maintained for 21 to 22 days. The data suggest that immunosuppressed gerbils provide a reliable rodent model of persistent C. hominis infection.

  18. Therapeutic drug monitoring of immunosuppressant drugs by high-performance liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Taylor, Paul J

    2004-04-01

    The currently expanding range of immunosuppressant agents has placed new challenges on therapeutic drug-monitoring (TDM) services. Many of these drugs require the measurement of concentrations with subsequent dosage adjustment to maximize efficacy while minimizing toxicity. HPLC-mass spectrometry (HPLC-MS) is a relatively new technique for drug quantification and thus TDM of immunosuppressant drugs. Although mass spectrometry relies on producing, differentiating, and detecting ions in the gas phase, the development of the atmospheric pressure ionization interface (electrospray and chemical ionization) has enabled the direct coupling of solution introduction of compounds, via HPLC, to the mass analyzer. The impetus for using HPLC-MS for immunosuppressant measurement has come from the highly potent low-dose immunosuppressant drugs tacrolimus and sirolimus, which have low nanogram per milliliter circulating concentrations. A number of strategies have been reported for sample preparation and ways to automate these processes with solid-phase extraction and 2-dimensional chromatography. The disadvantages of HPLC-MS are initial cost of equipment and availability of suitably skilled scientific staff. The advantages of HPLC-mass spectrometry are high sensitivity, specificity, small sample requirements, minimal sample preparation, rapid throughput, and simultaneous measurement. Further, scientists have the ability to develop methods to measure new immunosuppressant drugs by HPLC-MS before commercial assays become available. With potential applications increasing in immunosuppressive drug monitoring, it can be envisaged that HPLC-MS may become standard equipment in TDM laboratories of the future.

  19. mTHPC Mediated, Systemic Photodynamic Therapy (PDT) for Nonmelanoma Skin Cancers : Case and Literature Review

    NARCIS (Netherlands)

    Horlings, Rudolf K.; Terra, Jorrit B.; Witjes, Max J. H.

    2015-01-01

    Background and Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat

  20. Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Pascher, Andreas; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Brockmann, Jens; Andrassy, Joachim; Banas, Bernhard; Jauch, Karl-Walter

    2012-04-01

    Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  1. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

    Science.gov (United States)

    O'Leary, Jacqueline G.; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

  2. [Childhood steroid-dependent idiopathic nephrotic syndrome: Predictive factors for the need of immunosuppressive treatment].

    Science.gov (United States)

    Golay, M; Douillard, A; Nagot, N; Fila, M; Ichay, L; Dalla Vale, F; Tenenbaum, J; Morin, D

    2017-11-01

    More than half of the children with idiopathic nephrotic syndrome become steroid-dependent (or frequent relapsers) and will later require the use of complementary treatment aiming to reduce steroids' side effects and to limit the number of proteinuria relapses. It appears important to identify these children as early as possible in order to adapt their treatment. The aim of this study was to analyze the population of children, under 18 years of age, diagnosed between 1/01/2000 and 31/05/2015 with an idiopathic nephrotic syndrome and followed at the Montpellier University Hospital to search for criteria predictive of steroid-sparing agent use. In this retrospective study of children with idiopathic nephrotic syndrome, the exclusion criteria were primary steroid resistance and children with no proteinuria relapse after diagnosis. Eighty-four children (54 boys) were included in this study. The mean follow-up duration was 5.5 years (0.75-16). The mean age at diagnosis was 4.6 years. Sixty-five children (77%) received at least one steroid-sparing agent during their follow-up, within a mean 10 months after diagnosis. In these patients, the first relapse of the disease occurred earlier when compared with the children who were maintained on steroid alone (4 months vs 7 months; P<0.001). The use of methylprednisolone pulses to obtain a remission, the cumulative dose of steroid treatment, and the number of proteinuria relapses were also significantly correlated with the use of complementary immunosuppressive therapy. We found no predictive criteria of the use of steroid-sparing agents at diagnosis in our population of children. Nevertheless, with the steroid regimen used, the time within which the first proteinuria relapse occurred appears to be a significant criterion for the secondary use of a steroid-sparing agent. These data should be taken into account when choosing the treatment regimen. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications

    OpenAIRE

    Pourmand, G. R.; Dehghani, S.; Saraji, A.; Khaki, S.; Mortazavi, S. H.; Mehrsai, A.; Sajadi, H.

    2012-01-01

    Background: Wound healing disorders are probably the most common post-transplantation surgical complications. It is thought that wound healing disturbance occurs due to antiproliferative effects of immunosuppressive drugs. On the other hand, success of transplantation is dependent on immunosuppressive therapies. Antihuman thymocyte globulin (ATG) has been widely used as induction therapy but the impact of this treatment on wound healing is not fully understood. Objective: To investigate wound...

  4. Severe neuro-Behcet’s disease treated with a combination of immunosuppressives and a TNF-inhibitor.

    Directory of Open Access Journals (Sweden)

    Fatma Nur Korkmaz

    2016-10-01

    Full Text Available Abstract/ Resumo Behcet's disease (BD is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD, is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day, iv cylophosphamide (1g and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in

  5. Immunosuppressive and autoimmune effects of thimerosal in mice

    International Nuclear Information System (INIS)

    Havarinasab, S.; Haeggqvist, B.; Bjoern, E.; Pollard, K.M.; Hultman, P.

    2005-01-01

    compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury

  6. The non-immunosuppressive management of childhood nephrotic syndrome.

    Science.gov (United States)

    McCaffrey, James; Lennon, Rachel; Webb, Nicholas J A

    2016-09-01

    Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases found in the paediatric population and is associated with significant complications, including infection and thrombosis. A high proportion of children enter sustained remission before adulthood, and therapy must therefore mitigate the childhood complications, while minimising the long-term risk to health. Here we address the main complications of INS and summarise the available evidence and guidance to aid the clinician in determining the appropriate treatment for children with INS under their care. Additionally, we highlight areas where no consensus regarding appropriate management has been reached. In this review, we detail the reasons why routine prophylactic antimicrobial and antithrombotic therapy are not warranted in INS and emphasise the conservative management of oedema. When pharmacological intervention is required for the treatment of oedema, we provide guidance to aid the clinician in determining the appropriate therapy. Additionally, we discuss obesity and growth, fracture risk, dyslipidaemia and thyroid dysfunction associated with INS. Where appropriate, we describe how recent developments in research have identified potential novel therapeutic targets.

  7. Rheumatological patients undergoing immunosuppressive treatments and parasitic diseases: a review of the literature of clinical cases and perspectives to screen and follow-up active and latent chronic infections.

    Science.gov (United States)

    Fabiani, Silvia; Bruschi, Fabrizio

    2014-01-01

    Nowadays, several potent immunosuppressive drugs are available for patients with rheumatologic disorders. In general, these treatments are acceptably well tolerated. Nevertheless, in patients with rheumatic diseases, who are taking immunosuppressive drugs, an increased risk of bacterial, viral and fungal, as well as parasitic infections, exists. We have reviewed literature, on PubMed library, on the topic 'parasitic infections in rheumatic disease patients treated with immunosuppressive drugs, including biological therapies'. We used no language or time restrictions. Search was concluded on January 15th 2014. We grouped all parasitic events among rheumatologic, therapeutically immuosuppressed, patients to estimate the magnitude of this risk. Then we gave our viewpoint in the perspective to screen and follow-up for active and latent chronic parasitoses, developing an hypothetical flow-chart. From data published in the literature the real burden of parasitoses, among patients with rheumatic diseases treated with immunosuppressive treatments, can not be estimated. Nevertheless, a positive trend on publication number exists, probably due to more than one reason: i) the increasing number of patients treated, especially with more than one immunosuppressive treatment, including new biological agents; ii) the increasing number of individuals who move from the north to the south of the world (endemic areas for parasitic infections) and vice versa, due to globalisation, and iii) the fact that more attention is paid for notification/publication of cases. Considering parasitic infections as emerging and potentially serious in their evolution, additional strategies for the prevention, careful screening and follow-up, with a high level of suspicion, identification, and pre-emptive therapy are necessary in candidate patients for biological agents.

  8. Symptom Experience Associated With Immunosuppressive Medications in Chinese Kidney Transplant Recipients.

    Science.gov (United States)

    Teng, Sha; Zhang, Shuping; Zhang, Wenxin; Lin, Xiaohong; Shang, Yabin; Peng, Xiao; Liu, Hongxia

    2015-09-01

    Kidney transplant recipients require lifelong treatment with immunosuppressive medications to avoid graft rejection and graft loss. Symptoms experienced may influence recipients' perceived quality of life and medication adherence. The purpose of this study was to evaluate the symptom experience associated with immunosuppressive medications in adult kidney transplant recipients and to explore the association between the symptom experience and adherence to immunosuppressive medications. A cross-sectional design was used. The study was conducted in a general hospital in China from October 2013 to September 2014. A total of 231 recipients with a follow-up of at least 1 year after kidney transplantation were included. Symptom experience associated with immunosuppressive medications was measured by the 13-item Symptom Experience of Immunosuppressive-related Side Effects Scale. Self-reported adherence to immunosuppressive medications was assessed using the Adherence with Immunosuppressive Medication Scale. Ridit analysis was used to rank symptom distress items. A proportion of 60.6% of recipients were male; the time after kidney transplantation was arbitrarily divided into a short-term cohort (1-4 years) and a long-term cohort (4-16 years) according to the median duration of follow-up (4 years). High blood pressure, hair loss, and tiredness were the three most distressing symptoms over all items of the whole sample. High blood pressure was the most distressing symptom for the 1- to 4-year cohort and the 4- to 16-year cohort. For men high blood pressure was the most distressing symptom, whereas for women hair loss was the most distressing symptom. Recipients in the 4- to 16-year cohort perceived a higher level of symptom distress compared with those in the 1- to 4-year cohort, especially in excess hair growth and difficulty sleeping. A negative relationship was found between symptom distress and adherence to immunosuppressive medications (r = -.541, p = .000). Recipients

  9. The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation.

    Science.gov (United States)

    Rangel, Erika B

    2012-12-01

    Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups. This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed. Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.

  10. Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity.

    Science.gov (United States)

    Yamahara, J; Shimoda, H; Matsuda, H; Yoshikawa, M

    1996-09-01

    Potent immunosuppressants, the dimeric sesquiterpene thioalkaloids, 6-hydroxythiobinupharidine (2), 6,6'-dihydroxythiobinupharidine (3), 6-hydroxythionuphlutine B (5) and 6'-hydroxythionuphlutine B (6), were isolated from a natural medicine, Nupharis Rhizoma, the rhizoma of Nuphar pumilum (TIMM.) DC., through bioassay-guided separation together with five quinolizidine alkaloids (8, 9, 10, 11, 12). Dimeric sesquiterpene thioalkaloids (2, 3, 5, 6) were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mice spleen cells at 10(-6) M concentration. At this concentration, 2, 5 and 6 were found to exhibit no cytotoxicity to mice spleen cells, and 3 also showed only a little cytotoxicity. In addition, the inhibitory activity of several Nuphar alkaloids, dimeric sesquiterpene thioalkaloids (1, 4, 7, 8), and monomeric sesquiterpene alkaloids (9, 10, 11, 12) on anti-sheep erythrocyte plaque forming cell formation was examined and some structural requirement of Nuphar alkaloid for immunosuppressive activity was determined.

  11. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  12. Modified Aloe Polysaccharide Restores Chronic Stress-Induced Immunosuppression in Mice.

    Science.gov (United States)

    Lee, Youngjoo; Im, Sun-A; Kim, Jiyeon; Lee, Sungwon; Kwon, Junghak; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2016-09-30

    Chronic stress generally experienced in our daily lives; is known to augment disease vulnerability by suppressing the host immune system. In the present study; the effect of modified Aloe polysaccharide (MAP) on chronic stress-induced immunosuppression was studied; this Aloe compound was characterized in our earlier study. Mice were orally administered with MAP for 24 days and exposed to electric foot shock (EFS; duration; 3 min; interval; 10 s; intensity; 2 mA) for 17 days. The stress-related immunosuppression and restorative effect of MAP were then analyzed by measuring various immunological parameters. MAP treatment alleviated lymphoid atrophy and body weight loss. The numbers of lymphocyte subsets were significantly normalized in MAP-treated mice. Oral administration of MAP also restored the proliferative activities of lymphocytes; ovalbumin (OVA)-specific T cell proliferation; antibody production; and the cell killing activity of cytotoxic T lymphocytes. In summary; oral administration of MAP ameliorated chronic EFS stress-induced immunosuppression.

  13. Quality of life of older patients undergoing renal transplantation: finding the right immunosuppressive treatment.

    Science.gov (United States)

    Perlman, Rachel L; Rao, Panduranga S

    2014-02-01

    Kidney transplantation is currently the best treatment for end-stage renal disease, both in terms of mortality benefit and quality of life (QOL). Elderly patients are a rapidly growing subset of the kidney transplant waiting list. While it is clear that elderly individuals have a mortality benefit from kidney transplant, it is less clear how to make sure these individuals benefit from optimal QOL following transplant. Several studies demonstrate superiority of some immunosuppressive regimens over others in the QOL domain. Tacrolimus has been shown to be associated with better QOL than cyclosporine (ciclosporin), as has corticosteroid-free immunosuppressive regimens. Similarly, patients on drug regimens, which tend to lessen the side effects, report better QOL. However, these studies are observational or cross-sectional and not focused exclusively on the elderly patient. More studies are needed to determine optimal immunosuppression regimens for elderly individuals. Additionally, further studies on determinants of QOL in elderly kidney transplant recipients are also needed.

  14. Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

    Directory of Open Access Journals (Sweden)

    JG Machado

    2010-01-01

    Full Text Available Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-γ, IL-2, IL-4 and IL-10 by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

  15. Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era

    DEFF Research Database (Denmark)

    Touma, Madeleine; Rasmussen, Line D; Martin-Iguacel, Raquel

    2017-01-01

    BACKGROUND: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. METHODS...

  16. Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus.

    Science.gov (United States)

    Lebonville, Christina L; Jones, Meghan E; Hutson, Lee W; Cooper, Letty B; Fuchs, Rita A; Lysle, Donald T

    2016-08-01

    Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. [Neurectodermal malignant tumor of the soft tissues after treatment with immunosuppressive agents of lipoid nephrosis].

    Science.gov (United States)

    Parlier, G; Bensman, A; Leverger, G; Boccon-Gibod, L; Gruner, M

    1992-02-01

    Immunosuppressive drugs are known to increase the risk of inducing neoplasia, especially acute leukaemia when high doses are used. A case of nephrosis in a 10 year-old boy treated with chlormethine (cumulative dose: 0.8 mg/kg) and chlorambucil (cumulative dose: 10 mg/kg) is reported. Four years after the beginning of the treatment an extraskeletal Ewing's sarcoma occurred. Since the review of literature failed to find any malignancy induced by such an immunosuppressive treatment for nephrosis, the question whether or not this extraskeletal Ewing's sarcoma was attributable to this treatment remains unanswered.

  18. The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Bannister, Wendy P; Kirk, Ole

    2012-01-01

    The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression.......The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression....

  19. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

    Directory of Open Access Journals (Sweden)

    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  20. Differentially expressed gene transcripts using RNA sequencing from the blood of immunosuppressed kidney allograft recipients.

    Directory of Open Access Journals (Sweden)

    Casey Dorr

    Full Text Available We performed RNA sequencing (RNAseq on peripheral blood mononuclear cells (PBMCs to identify differentially expressed gene transcripts (DEGs after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because it's not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in 32 adult kidney recipients, without clinical acute rejection (AR, treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline, week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2 (Striking Image compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s responsible for differential gene

  1. Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

    Science.gov (United States)

    Franco-Molina, Moisés A; Miranda-Hernández, Diana F; Mendoza-Gamboa, Edgar; Zapata-Benavides, Pablo; Coronado-Cerda, Erika E; Sierra-Rivera, Crystel A; Saavedra-Alonso, Santiago; Taméz-Guerra, Reyes S; Rodríguez-Padilla, Cristina

    2016-01-01

    Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25+ expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25+ than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4+ cells (CD4+, CD4+CD25+, and CD4+CD25+Foxp3+) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment. PMID:26834483

  2. Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer

    NARCIS (Netherlands)

    J. Jans (Judith); G.A. Garinis (George); W. Schul; A. van Oudenaren (Adri); M.J. Moorhouse (Michael); M. Smid (Marcel); Y.-G. Sert (Yurda-Gul); A. van der Velde (Albertina); Y.M. Rijksen (Yvonne); F.R. de Gruijl (Frank); P.J. van der Spek (Peter); A. Yasui (Akira); J.H.J. Hoeijmakers (Jan); P.J. Leenen (Pieter); G.T.J. van der Horst (Gijsbertus)

    2006-01-01

    textabstractCyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type

  3. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  4. Factors modifying stress from adverse effects of immunosuppressive medication in kidney transplant recipients

    NARCIS (Netherlands)

    Rosenberger, J.; Geckova, A.M.; van Dijk, J.P.; Roland, R.; Groothoff, J.W.

    Introduction: The adverse effects of immunosuppression appear in the majority of patients with a negative impact on morbidity, mortality and quality of life. The group of adverse symptoms manifested as changes in appearance, mood and energy are often more stressful than serious metabolic changes

  5. IL-10 is an effector molecule mediating urocanic acid-induced immunosuppression

    Czech Academy of Sciences Publication Activity Database

    Krulová, Magdalena; Kuffová, Lucia; Zajícová, Alena; Filipec, M.; Holáň, Vladimír

    1999-01-01

    Roč. 31, - (1999), s. 1218-1219 ISSN 0041-1345 R&D Projects: GA MZd IZ3964; GA ČR GA310/97/1261; GA MŠk VS97099 Keywords : immunosuppression, urocanic acid Subject RIV: EC - Immunology Impact factor: 0.590, year: 1999

  6. Steroid-free immunosuppression after renal transplantation-long-term experience from a single centre

    DEFF Research Database (Denmark)

    El-Faramawi, Mohamad; Rohr, Nils; Jespersen, Bente

    2006-01-01

    BACKGROUND: A steroid-free immunosuppressive protocol may improve the general well-being of patients, but long-term renal graft survival has been a concern. METHODS: In a retrospective clinical study, 329 consecutive transplantations with renal grafts at our centre during the period 1995-2004, were...

  7. Long-Term Outcome of Early Combined Immunosuppression Versus Conventional Management in Newly Diagnosed Crohn's Disease

    NARCIS (Netherlands)

    Hoekman, Daniël R.; Stibbe, Judith A.; Baert, Filip J.; Caenepeel, Philip; Vergauwe, Philippe; de Vos, Martine; Hommes, Daniel W.; Benninga, Marc A.; Vermeire, Severine A.; D'Haens, Geert R.

    2018-01-01

    Long term outcomes of early combined immunosuppression (top-down) compared to conventional management (step-up) in recently diagnosed Crohn's disease (CD) are unknown. We aimed to investigate long-term outcomes of participants of the Step-up/Top-down-trial. Trial participants' medical records were

  8. Fatal tick-borne encephalitis in an immunosuppressed 12-year-old patient

    Czech Academy of Sciences Publication Activity Database

    Chmelík, V.; Chrdle, A.; Růžek, Daniel

    2016-01-01

    Roč. 74, 1 January (2016), s. 73-74 ISSN 1386-6532 R&D Projects: GA ČR GAP502/11/2116 Institutional support: RVO:60077344 Keywords : Tick-borne encephalitis * immunosuppressed patient * fatal case * haemophagocytic lymphohistiocytosis Subject RIV: EE - Microbiology, Virology Impact factor: 3.051, year: 2016

  9. Response of transplant recipients to influenza vaccination based on type of immunosuppression: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Reza Karbasi-Afshar

    2015-01-01

    Full Text Available Influenza vaccination is widely used in transplant recipients, but there is little known about the significance and correlating factors of its effectiveness. In the current study, we reviewed the existing literature on clinical trials performed in transplant recipients on the effectiveness of influenza vaccination and to evaluate the relevance of the type of immunosuppression employed in these patients on the humoral reaction to the vaccine. A comprehensive search of the literature was performed through Pubmed and Google Scholar to find reports indicating immunogenicity of influenza vaccination in transplant patients. Finally, data from 15 published clinical trials were included in the meta-analysis. Data of 947 transplant recipients retrieved from 15 clinical trials investigating the immunogenicity of influenza vaccination were analyzed in this meta-analysis. Analysis showed significantly lower rates of sero-conversion among transplant recipients receiving mycophenolate mofetil (MMF than other immunosuppressive agents (relative risk: 0.724; 95% confidence interval: 0.596-0.880; P = 0.001. No significant correlation was found with tacrolimus, sirolimus, cyclosporine and azathioprine. Different immunosuppressive agents seem to have different effects on the humoral response rate to influenza vaccination, with MMF having the most significant deleterious effect. The limited and controversial data available in the literature do not support any differential effect for other immunosuppressive agents.

  10. [Etiopathogenesis of aplastic anemia and of the severe form treated with immunosuppression and bone marrow transplantation].

    Science.gov (United States)

    Dulley, F L; Lotério, H A; Massumoto, C M; Llacer, P E; Chamone, D de A

    1989-01-01

    Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.

  11. Synthesis and characterization of an epimer of tacrolimus, an immunosuppressive drug

    DEFF Research Database (Denmark)

    Skytte, Dorthe Mondrup; Frydenvang, Karla Andrea; Hansen, Liselotte

    2010-01-01

    8-Epitacrolimus (2), a new l-pipecolic acid macrolide lactone, was obtained by base-catalyzed epimerization of tacrolimus (FK-506, 1), an important immunosuppressive drug, and its structure determined by a single-crystal X-ray diffraction method. The compound was fully characterized by spectrosco...

  12. Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Hallas, Jesper

    2015-01-01

    Severely immunosuppressed individuals have a strongly increased risk of cervical cancer. In patients with autoimmune diseases (AID), who have defects in their immune system and receive immunosuppressants, the risk of cervical cancer is less clear. We conducted a cohort study, using Danish...

  13. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

    DEFF Research Database (Denmark)

    Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard

    2015-01-01

    with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...

  14. Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As Augments Dermal Wound Healing in Immunosuppressed Rats.

    Directory of Open Access Journals (Sweden)

    Gaurav K Keshri

    Full Text Available Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM or low-level laser (light therapy (LLLT emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions. The present study was therefore undertaken to evaluate the photobiomodulatory effects of 810 nm diode laser (40 mW/cm2; 22.6 J/cm2 with pulsed (10 and 100 Hz, 50% duty cycle and continuous wave on full-thickness excision-type dermal wound healing in hydrocortisone-induced immunosuppressed rats. Results clearly delineated that 810 nm PBM at 10 Hz was more effective over continuous and 100 Hz frequency in accelerating wound healing by attenuating the pro-inflammatory markers (NF-kB, TNF-α, augmenting wound contraction (α-SM actin, enhancing cellular proliferation, ECM deposition, neovascularization (HIF-1α, VEGF, re-epithelialization along with up-regulated protein expression of FGFR-1, Fibronectin, HSP-90 and TGF-β2 as compared to the non-irradiated controls. Additionally, 810 nm laser irradiation significantly increased CCO activity and cellular ATP contents. Overall, the findings from this study might broaden the current biological mechanism that could be responsible for photobiomodulatory effect mediated through pulsed NIR 810 nm laser (10 Hz for promoting dermal wound healing in immunosuppressed subjects.

  15. Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As) Augments Dermal Wound Healing in Immunosuppressed Rats.

    Science.gov (United States)

    Keshri, Gaurav K; Gupta, Asheesh; Yadav, Anju; Sharma, Sanjeev K; Singh, Shashi Bala

    2016-01-01

    Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM) or low-level laser (light) therapy (LLLT) emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions. The present study was therefore undertaken to evaluate the photobiomodulatory effects of 810 nm diode laser (40 mW/cm2; 22.6 J/cm2) with pulsed (10 and 100 Hz, 50% duty cycle) and continuous wave on full-thickness excision-type dermal wound healing in hydrocortisone-induced immunosuppressed rats. Results clearly delineated that 810 nm PBM at 10 Hz was more effective over continuous and 100 Hz frequency in accelerating wound healing by attenuating the pro-inflammatory markers (NF-kB, TNF-α), augmenting wound contraction (α-SM actin), enhancing cellular proliferation, ECM deposition, neovascularization (HIF-1α, VEGF), re-epithelialization along with up-regulated protein expression of FGFR-1, Fibronectin, HSP-90 and TGF-β2 as compared to the non-irradiated controls. Additionally, 810 nm laser irradiation significantly increased CCO activity and cellular ATP contents. Overall, the findings from this study might broaden the current biological mechanism that could be responsible for photobiomodulatory effect mediated through pulsed NIR 810 nm laser (10 Hz) for promoting dermal wound healing in immunosuppressed subjects.

  16. Renal Transplant Recipients: The Factors Related to Immunosuppressive Medication Adherence Based on the Health Belief Model.

    Science.gov (United States)

    Kung, Pen-Chen; Yeh, Mei Chang; Lai, Ming-Kuen; Liu, Hsueh-Erh

    2017-10-01

    Kidney transplant failures are caused primarily by lack of adherence to immunosuppressive medication regimens by patients after transplantation. A number of studies have indicated that health-related beliefs are an effective predictor of health-related behavior. The aim of this study is to understand the influence of the personal characteristics and health-related beliefs of patients on adherence to treatment with immunosuppressive medication based on the Health Belief Model. This cross-sectional study distributed questionnaires to patients who had been recruited via purposive sampling at one medical center in Taipei. All of the potential participants had undergone kidney transplantation at least 6 months previously. The self-developed questionnaire collected data in three areas: personal characteristics, health-related beliefs regarding transplant rejection, and adherence to the immunosuppressive medication regimen. One hundred twenty-two valid questionnaires were received. The collected data were analyzed using descriptive statistics, independent t test, one-way analysis of variance, Pearson's correlation, and multiple regression. Participants who had received dialysis treatment or had experienced rejection perceived susceptibility to rejection more strongly than those who had not. Participants who had undergone transplantation in Taiwan, had experienced more drug-related symptoms, or had contracted severe to extremely severe infections in the past showed lower rates of adherence to treatment with immunosuppressive medication. Adherence to medication regimens correlated negatively with length of time since transplantation. Length of time since transplantation, drug-related symptoms, perceived susceptibility to rejection, and perceived benefits of treatment were identified as major predictors of adherence to immunosuppressive medication regimens. The results partially conformed to the concepts of the Health Belief Model. Perceived susceptibility to rejection and

  17. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    Christine eNeudoerfl

    2013-02-01

    Full Text Available In the context of kidney transplantation, little is known about the involvement of NK cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e. calcineurin-inhibitors like CyclosporinA vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56dim NK cells was observed with significant differences between CyclosporinA- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR and increased CD94/NKG2A expression in CD56dim NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with PBMC of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and IFN--production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus,NK cells can serve as sensors

  18. Alleviation of cyclophosphamide-induced immunosuppression in Wistar rats by onion lectin (Allium cepa agglutinin).

    Science.gov (United States)

    Kumar, Vaddi P; Venkatesh, Yeldur P

    2016-06-20

    In various traditional medicines, onion has been classified as an immune-boosting food. Recent studies have claimed this property due to the presence of bioactive organosulfur compounds, prebiotic fructo-oligosaccharides and an immunomodulatory protein, lectin (Allium cepa agglutinin; ACA) (Prasanna and Venkatesh, 2015. Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro. Int. Immunopharmacol. vol. 26, pp. 304-313). The aim of this study was to evaluate the immunoprotective properties of ACA in normal and cyclophosphamide (CP; 100μg/kg)-induced immunosuppressed Wistar rats. Wistar rats were administrated different doses of ACA (1, 10, and 100μg) to respective groups in normal as well as immunosuppressed animals. The effect of ACA on the status of immune organs was assessed by examining the splenic and thymic indices, and histopathological changes. The biomarkers for humoral immunity (serum IgG and IgA levels) and serum pro-inflammatory markers (COX-2, TNF-α and IL-10) were measured by ELISA. ACA showed immunoprotective properties by significantly promoting the restoration of lymphoid cell count by ~6 fold vs. model control (immunosuppressed animals) and promotes the immune response significantly (~1.5-fold) in CP-induced immunosuppressed animals compared to model control; production of pro-inflammatory molecules (COX-2 and nitric oxide) and expression levels of immune regulatory molecule (TNF-α) were elevated in a dose-dependent manner. The observed in vivo results suggest that ACA has the potential to be used as a nutritional therapeutic to boost the immune status of immunosuppressed subjects brought about by CP administration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Long-Term Outcomes of High-Risk Keratoplasty in Patients Receiving Systemic Immunosuppression.

    Science.gov (United States)

    Chow, Sing-Pey; Cook, Stuart D; Tole, Derek M

    2015-11-01

    Immunological graft rejection after corneal transplantation remains the leading cause of graft failure. Systemic immunosuppression is used for keratoplasty at a high risk of rejection to improve graft survival. We examined the long-term outcomes of high-risk corneal grafts in patients receiving systemic immunosuppression. Thirty-five corneal transplants with a high risk of rejection were identified from 29 patients within a regional immunosuppression service in the United Kingdom. Definition of keratoplasty at "high risk" of rejection included one or more of the following: a history of ipsilateral graft rejection and/or failure, 2 or more quadrants of stromal vascularization, perforation or ocular inflammation at the time of surgery, presence of atopy, and a large-diameter (≥9 mm) graft. Median follow-up duration was 5 years after transplantation. Graft survival at 5 years in patients receiving systemic immunosuppression was 73.5%. Rejection episodes occurred in 14 grafts (40%); these episodes were reversible in 10 grafts (71%). Indications for transplantation were mostly visual (n = 19; 54%) and tectonic (n = 14; 40%). Eighteen grafts (51%) had 2 or more high-risk characteristics. Most patients (n = 20; 69%) received monotherapy, commonly with tacrolimus (n = 15; 52%) or mycophenolate mofetil (n = 8; 28%). Three patients (10%) experienced severe systemic side effects. Median "day-to-day" logMAR visual acuity was 0.5 in grafts for all indications and 0.2 for visual indications. Systemic immunosuppression in patients with high-risk keratoplasty seems to improve graft survival with a median follow-up duration of 5 years and is tolerated by most patients. Despite rejection episodes occurring in 40% of grafts, these were mostly reversible.

  20. Immunosuppressive activity of an aqueous Viola tricolor herbal extract.

    Science.gov (United States)

    Hellinger, Roland; Koehbach, Johannes; Fedchuk, Halyna; Sauer, Barbara; Huber, Roman; Gruber, Christian W; Gründemann, Carsten

    2014-01-01

    inhibit proliferation of activated lymphocytes in an IL-2 dependent manner. The findings provide a rationale for use of herbal Viola preparations in the therapy of disorders related to an overactive immune system. However, further studies to evaluate its clinical potency and potential risks have to be performed. © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis treated by interferon-free directly acting antivirals for HCV in the absence of immunosuppressant.

    Science.gov (United States)

    Obata, Fumiaki; Murakami, Taichi; Miyagi, Junko; Ueda, Sayo; Inagaki, Taizo; Minato, Masanori; Ono, Hiroyuki; Nishimura, Kenji; Shibata, Eriko; Tamaki, Masanori; Yoshimoto, Sakiya; Kishi, Fumi; Kishi, Seiji; Matsuura, Motokazu; Nagai, Kojiro; Abe, Hideharu; Doi, Toshio

    2017-05-01

    Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection. The standard therapy of a chronic HCV infection is IFN monotherapy or IFN combined with ribavirin; however, after the introduction of direct-acting antivirals (DAAs), the standard therapy for patients with HCV genotype 1 has dramatically changed. We report a case of HCV-associated cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir, which are IFN-free DAAs for HCV, in combination with angiotensin II receptor blocker without immunosuppressive therapy. The patient developed severe nephrotic syndrome with progressive kidney dysfunction. Blood examination revealed a high copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia of IgM-κ, and hypocomplementemia. Histological analysis showed MPGN type 1. These findings were compatible with those observed in HCV-associated cryoglobulinemic MPGN. This case offers original evidence for the application of newer generation of IFN-free DAAs in the treatment of HCV-associated cryoglobulinemic nephropathy.

  2. Trends of Immunosuppression and Outcomes Following Liver Transplantation: An Analysis of the United Network for Organ Sharing Registry.

    Science.gov (United States)

    Cheng, Elaine Y; Everly, Matthew J

    2014-01-01

    Advances in immunosuppression (IS) agents and strategies have resulted in reduced rejection rates and improved survival outcomes after liver transplantation. The use of induction and maintenance IS agents is both associated with reductions in acute rejection (AR) risk within the first 6 to 12 months posttransplant and with superior failure-free survival. With the lowered incidence of allograft losses attributable to rejection, the long-term sequelae of IS have become the major therapeutic challenge. The long-term use of calcineurin inhibitors and corticosteroids in maintenance immunotherapy regimens has been implicated in the development of renal dysfunction, infections, metabolic derangements, de novo and recurrent malignancies, and the propagation of hepatitis C virus reinfection. Our analysis of the United Network for Organ Sharing registry shows the use of induction and maintenance therapy is each associated with reductions in AR risk, thereby improving post-transplant survival. The administration of intensive induction regimens appears to be safe and exhibits an additive beneficial effect. Therefore, the use of intensive induction regimens may be warranted to allow for reductions in long-term maintenance IS to minimize drug toxicities while preserving graft outcomes.

  3. Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors

    Directory of Open Access Journals (Sweden)

    Chuan Jin

    2014-01-01

    Full Text Available Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the “rapid expansion protocol” (REP, which utilizes OKT-3, interleukin (IL-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion. Here, we demonstrate that when irradiated and preactivated allosensitized allogeneic lymphocytes (ASALs are used as helper cells to license OKT3-armed allogeneic mature dendritic cells (DCs, together they expand target T cells of high quality. The ASAL/DC combination yields an enriched Th1-polarizing cytokine environment (interferon (IFN-γ, IL-12, IL-2 and optimal costimulatory signals for T-cell stimulation. When genetically engineered antitumor T cells were expanded by this coculture system, they showed better survival and cytotoxic efficacy under oxidative stress and immunosuppressive environment, as well as superior proliferative response during tumor cell killing compared to the REP protocol. Our result suggests a robust ex vivo method to expand T cells with improved quality for adoptive cancer immunotherapy.

  4. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  5. Comparison of second-line immunosuppressants for childhood refractory nephrotic syndrome: a systematic review and network meta-analysis.

    Science.gov (United States)

    Fu, Hai-Dong; Qian, Gu-Ling; Jiang, Zheng-Yang

    2017-01-01

    Although, most patients respond initially to therapy for nephrotic syndrome, about 70% of patients have a relapse. Currently, there is no consensus about the most appropriate second-line agent in children who continue to suffer a relapse. This network meta-analysis was designed to compare the efficacy and safety of the commonly used immunosuppressive agents in second-line therapeutic agents (ie, cyclophosphamide, cyclosporine, tacrolimus and mycophenolate mofetil) for refractory childhood nephrotic syndrome. MEDLINE, Cochrane, EMBASE and Google Scholar databases were searched until October 17, 2015 using the following search terms: cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil and childhood nephrotic syndrome. Randomized controlled trials, prospective 2-arm studies and cohort studies were included. 7 studies with 391 patients were included. Bayesian network meta-analysis found that treatment with mycophenolate mofetil had the greatest odds of relapse compared with tacrolimus (pooled OR=49.72, 95% credibility interval (CrI) 1.65 to 2483.32), cyclophosphamide (pooled OR=72.05, 95% CrI 1.44 to 13633.33) and cyclosporine (pooled OR=11.42, 95% CrI 1.03 to 131.60). Rank probability analysis found cyclophosphamide was the best treatment with the lowest relapse rate as compared with other treatments (rank probability=0.58), and tacrolimus was ranked as the second best (rank probability=0.38). Our findings support the use of cyclophosphamide and tacrolimus in treating children with relapsing nephrotic syndrome. Copyright © 2016 American Federation for Medical Research.

  6. Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland).

    Science.gov (United States)

    Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

    2016-04-01

    Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L(-1) downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Brief Report: Proteasomal Indoleamine 2,3-Dioxygenase Degradation Reduces the Immunosuppressive Potential of Clinical Grade-Mesenchymal Stromal Cells Undergoing Replicative Senescence.

    Science.gov (United States)

    Loisel, Séverine; Dulong, Joëlle; Ménard, Cédric; Renoud, Marie-Laure; Meziere, Nadine; Isabelle, Bezier; Latour, Maëlle; Bescher, Nadège; Pedeux, Rémy; Bertheuil, Nicolas; Flecher, Erwan; Sensebé, Luc; Tarte, Karin

    2017-05-01

    Owing to their immunosuppressive properties, mesenchymal stromal cells (MSCs) obtained from bone marrow (BM-MSCs) or adipose tissue (ASCs) are considered a promising tool for cell therapy. However, important issues should be considered to ensure the reproducible production of efficient and safe clinical-grade MSCs. In particular, high expansion rate, associated with progressive senescence, was recently proposed as one of the parameters that could alter MSC functionality. In this study, we directly address the consequences of replicative senescence on BM-MSC and ASC immunomodulatory properties. We demonstrate that MSCs produced according to GMP procedures inhibit less efficiently T-cell, but not Natural Killer (NK)- and B-cell, proliferation after reaching senescence. Senescence-related loss-of-function is associated with a decreased indoleamine 2,3-dioxygenase (IDO) activity in response to inflammatory stimuli. In particular, although STAT-1-dependent IDO expression is transcriptionally induced at a similar level in senescent and nonsenescent MSCs, IDO protein is specifically degraded by the proteasome in senescent ASCs and BM-MSCs, a process that could be reversed by the MG132 proteasome inhibitor. These data encourage the use of appropriate quality controls focusing on immunosuppressive mechanisms before translating clinical-grade MSCs in the clinic. Stem Cells 2017;35:1431-1436. © 2017 AlphaMed Press.

  8. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Directory of Open Access Journals (Sweden)

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  9. Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Miettinen, Johanna A., E-mail: johanna.miettinen@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Pietilae, Mika [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Salonen, Riikka J. [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Ohlmeier, Steffen [Proteomics Core Facility, Biocenter Oulu, Department of Biochemistry, University of Oulu, P.O. Box 3000, FIN-90014 Oulu (Finland); Ylitalo, Kari; Huikuri, Heikki V. [Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland); Lehenkari, Petri [Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu (Finland)

    2011-04-01

    Mesenchymal stem cells (MSCs) are widely used in experimental treatments for various conditions that involve normal tissue regeneration via inflammatory repair. It is known that MSCs can secrete multiple soluble factors and suppress inflammation. Even though the effect of MSCs on inflammation has been extensively studied, the effect of inflammation on MSCs is poorly understood. One of the major cytokines released at the site of inflammation is tumor necrosis factor alpha (TNF-{alpha}) which is known to induce MSC invasion and proliferation. Therefore, we wanted to test the effects of TNF-{alpha} exposure on MSCs derived from human bone marrow. We found, as expected, that cell proliferation was significantly enhanced during TNF-{alpha} exposure. However, according to the cell surface marker analysis, the intensity of several antigens in the minimum criteria panel for MSCs proposed by International Society of Cellular Therapy (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs were not fulfilled. In addition, TNF-{alpha} exposure resulted in a significant but transient increase in human leukocyte antigen and CD54 expression. Additional proteomic analysis by two-dimensional difference gel electrophoresis and mass spectrometry revealed three proteins whose expression levels decreased and 8 proteins whose expression levels increased significantly during TNF-{alpha} exposure. The majority of these proteins could be linked to immunosuppressive and signalling pathways. These results strongly support reactive and immunosuppressive activation of MSCs during TNF-{alpha} exposure, which might influence MSC differentiation stage and capacity.

  10. Original paper Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression

    Directory of Open Access Journals (Sweden)

    Izabela Szczygielska

    2015-05-01

    Full Text Available Objectives : Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. Material and methods : The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases – 37 girls (74% and 13 boys (26%, aged 1.5–17.5 years – during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children – 28 girls (56% and 22 boys (44% aged 2–17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0–1–6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. Results: No protective antibody concentrations were found in 25 cases (50% in the group of diseased children and only in 2 children in the control group (4%. Conclusions : The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B.

  11. Biological therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Sivamani Raja

    2010-01-01

    Full Text Available The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-α agents have been associated with a variety of serious and "routine" opportunistic infections.

  12. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

    Science.gov (United States)

    Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

    2017-06-01

    Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

  13. Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

    Science.gov (United States)

    Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

    2012-07-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

  14. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases...... and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according...... to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113...

  15. Sentinel node status and immunosuppression: recurrence factors in localized Merkel cell carcinoma.

    Science.gov (United States)

    Jouary, Thomas; Kubica, Emeline; Dalle, Stéphane; Pages, Cecile; Duval-Modeste, Anne-Benedicte; Guillot, Bernard; Mansard, Sandrine; Saiag, Philippe; Aubin, François; Bedane, Christophe; Dalac, Sophie; Dompmartin, Anne; Granel-Brocard, Florence; Lok, Catherine; Stoebner, Pierre-Emmanuel; Lacour, Jean-Philippe; Leccia, Marie-Therese; Diallo, Abou; Ezzedine, Khaled; Mateus, Christina

    2015-09-01

    The prognostic value of the sentinel lymph node in Merkel cell carcinoma (MCC) has been examined previously in heterogeneous retrospective studies. The current retrospective study included a homogeneous population of patients with a localized MCC, all staged with sentinel lymph node biopsy. Factors associated with 3-year progression-free survival were analysed using logistic regression. The sentinel lymph node was positive in 32% of patients. The recurrence rate was 26.9%. In first analyses (n = 108), gender (p = 0.0115) and the presence of immunosuppression (p = 0.0494) were the only significant independent factors. In further analyses (n = 80), excluding patients treated with regional radiotherapy, sentinel lymph node status was the only significant prognostic factor (p = 0.0281). Immunosuppression and positive sentinel lymph node are associated with a worse prognosis in patients with MCC. Nodal irradiation impacts on the prognostic value of the sentinel lymph node status.

  16. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    International Nuclear Information System (INIS)

    Sonoda, Kazuhiko; Rapaport, F.T.

    1992-01-01

    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author)

  17. Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy

    International Nuclear Information System (INIS)

    Martins, Flavia Paiva Proenca; Gutfilen, Bianca

    2001-01-01

    Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed 99m Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

  18. A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Atiyah Patel

    2016-01-01

    Full Text Available Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi’s sarcoma.

  19. Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

    Science.gov (United States)

    Rosas-Taraco, Adrian G.; Perez-Liñan, Amira R.; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I.

    2012-01-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection. PMID:22547544

  20. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp

    DEFF Research Database (Denmark)

    Pierdomenico, Laura; Bonsi, Laura; Calvitti, Mario

    2005-01-01

    BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are currently being investigated in preclinical and clinical settings because of their multipotent differentiative capacity or, alternatively, their immunosuppressive function. The aim of this study was to evaluate dental pulp (DP......, respectively, assessed by a 3H-thymidine assay. CONCLUSIONS: Dental pulp is an easily accessible and efficient source of MSCs, with different kinetics and differentiation potentialities from MSCs as isolated from the bone marrow. The rapid proliferative capacity together with the immunoregulatory......) as a potential source of MSCs instead of bone marrow (BM). METHODS: Flow cytometric analysis showed that DP-MSCs and BM-MSCs were equally SH2, SH3, SH4, CD29 and CD 166 positive. The in vitro proliferative kinetics of MSCs were measured by 3H-thymidine incorporation uptake. The immunosuppressive function of MSCs...

  1. Synthesis and biological evaluation of α,β-unsaturated lactones as potent immunosuppressive agents.

    Science.gov (United States)

    Lee, Sun-Mi; Lee, Won-Gil; Kim, Young-Chul; Kim, Yong-Chul; Ko, Hyojin

    2011-10-01

    Compounds having α,β-unsaturated lactones display a variety of biological activities. Many research groups have tested both natural and unnatural α,β-unsaturated lactones for as-yet undiscovered biological properties. We synthesized α,β-unsaturated lactones with various substituents at the δ-position and studied their immunosuppressive effects, that is, the inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized, the benzofuran-substituted α,β-unsaturated lactone 4h showed the best inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes (IC(50)=66.9 nM) without cytotoxicity at 10 μM. The results indicated that 4h may be useful as a potent immunosuppressive agent, as well as in IL-2-related studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Severe diarrhoea due to Cystoisospora belli in renal transplant patient on immunosuppressive drugs.

    Science.gov (United States)

    Marathe, A; Parikh, K

    2013-01-01

    Cystoisospora belli, formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS) and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole) and Nitazoxanide.

  3. Severe diarrhoea due to Cystoisospora belli in renal transplant patient on Immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    A Marathe

    2013-01-01

    Full Text Available Cystoisospora belli , formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole and Nitazoxanide.

  4. Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment

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    Qiujun Guo

    2015-01-01

    Full Text Available Traditional Chinese medicine (TCM is an important complementary strategy for treating cancer in China. The mechanism is related to regulating the internal environment and remodeling the tumor immunosuppressive microenvironment (TIM. Herein we illustrate how TIM is reformed and its protumor activity on promoting tumor cell proliferation, angiogenesis and lymphangiogenesis, tumor invasion, and the oncogenicity of cancer stem cells. Furthermore we summarize the effects and mechanism of TCM on regulating TIM via enhancing antitumor immune responses (e.g., regulating the expression of MHC molecules and Fas/FasL, attenuating cancerigenic ability of cancer stem cells and remolding immunosuppressive cells (e.g., reversing immune phenotypes of T lymphocytes and tumor associated macrophages, promoting dendritic cells mature, restraining myeloid derived suppressor cells function, and regulating Th1/Th2 factors. We also reveal the bidirectional and multitargeting functions of TCM on regulating TIM. Hopefully, it provides new theoretical basis for TCM clinical practice in cancer treatment and prevention.

  5. Psychosocial Variables Associated with Immunosuppressive Medication Non-Adherence after Renal Transplantation

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    Jennifer Felicia Scheel

    2018-02-01

    Full Text Available IntroductionNon-adherence to immunosuppressive medication is regarded as an important factor for graft rejection and loss after successful renal transplantation. Yet, results on prevalence and relationship with psychosocial parameters are heterogeneous. The main aim of this study was to investigate the association of immunosuppressive medication non-adherence and psychosocial factors.MethodsIn 330 adult renal transplant recipients (≥12 months posttransplantation, health-related quality of life, depression, anxiety, social support, and subjective medication experiences were assessed, and their associations with patient-reported non-adherence was evaluated.Results33.6% of the patients admitted to be partially non-adherent. Non-adherence was associated with younger age, poorer social support, lower mental, but higher physical health-related quality of life. There was no association with depression and anxiety. However, high proportions of clinically relevant depression and anxiety symptoms were apparent in both adherent and non-adherent patients.ConclusionIn the posttransplant follow-up, kidney recipients with lower perceived social support, lower mental and higher physical health-related quality of life, and younger age can be regarded as a risk group for immunosuppressive medication non-adherence. In follow-up contacts with kidney transplant patients, physicians may pay attention to these factors. Furthermore, psychosocial interventions to optimize immunosuppressive medication adherence can be designed on the basis of this information, especially including subjectively perceived physical health-related quality of life and fostering social support seems to be of importance.

  6. Immunosuppression and Chagas disease; experience from a non-endemic country.

    Science.gov (United States)

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

    OpenAIRE

    Gallagher, Martin P.; Kelly, Patrick J.; Jardine, Meg; Perkovic, Vlado; Cass, Alan; Craig, Jonathan C.; Eris, Josette; Webster, Angela C.

    2010-01-01

    Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non–skin cancer (including melanoma) and skin c...

  8. Immunosuppressive drug assaying: A challenge for renal transplantation in the Northern Territory, Australia

    Directory of Open Access Journals (Sweden)

    Francesca Gagliardo

    2016-06-01

    Full Text Available Background Renal transplant patients of the Northern Territory (NT of Australia, suffer poor transplant outcomes including graft rejection, infection and increased mortality, therefore requiring stringent immunosuppressive drug assay monitoring. Best practice dictates that drug assay results should be received within 24 hours and at the most no later than 48 hours post blood collection. Assays from the Royal Darwin Hospital (RDH are processed at an interstate laboratory, therefore prolonging the time to dosage adjustment. Aims To assess the time delay that exists between blood sample collection at the Royal Darwin Hospital (RDH and the faxing of results from an interstate laboratory to RDH. Methods We conducted a retrospective audit of immunosuppressive drug assay samples and results between the 4th of January 2013 and the 22nd April 2014. Time delay was divided into intervals: T1: Total time between collections to faxing of results back to RDH, T2: Time between blood collection, sending of samples and reporting at an interstate laboratory, T3: Time between results reporting and the faxing of results back to RDH. Results A total of 389 drug assays from 49 renal transplant patients were analysed. Median times in hours (interquartile ranges were T1=53.48 (31.68-78.55, T2=47.18 (28.80-76.18, T3=2.70 (1.87-3.90. 13.3 per cent of the results led to the requirement for dosage changes with the potential risk of under-dosing or overdosing. Conclusion The long median time delay between sample collection and receiving of results illustrates the challenges of immunosuppression in this setting and the need for on-site immunosuppressive drug assaying.

  9. The regulatory role of immunosuppressants on immune abnormalities in acute pancreatitis

    OpenAIRE

    DUAN, LIGENG; MA, YU; CHI, JUNLIN; WANG, XU; WESLEY, ALEXANDER J.; CHEN, XIAOLI

    2013-01-01

    The uncontrolled progression of the inflammatory cascade is the main cause underlying the development of multiple organ dysfunction syndrome (MODS) in acute pancreatitis. In this study, we investigated the effects of several immunosuppressants on mitigating the systemic inflammatory reaction syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) associated with acute pancreatitis. A total of 93 male Sprague Dawley rats were divided into 5 groups: group 1 was the sham ...

  10. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    Science.gov (United States)

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

  11. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    Science.gov (United States)

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

  12. Electronically-measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation*

    Science.gov (United States)

    Israni, Ajay K.; Weng, Francis L.; Cen, Ye-Ying; Joffe, Marshall; Kamoun, Malek; Feldman, Harold I.

    2013-01-01

    Background Non-adherence with immunosuppressive medications can result in allograft rejection and eventually allograft loss. Methods In a racially diverse population, we utilized microelectronic cap monitors to determine the association of adherence with a single immunosuppressive medication and kidney allograft outcomes post-transplantation. This prospective cohort study enrolled 243 patients from eight transplant centers to provide adherence and kidney allograft outcomes data. To determine the association of adherence with change in estimated glomerular filtration rate (eGFR), we fit mixed effects models with the outcome being change in eGFR over time. We also fit Cox proportional hazards models to determine the association of adherence with time to persistent 25% and 50% decline in eGFR. Results The distribution of adherence post-transplant was as follows: 164 (68%), 49 (20%) and 30 (12%) had >85–100%, 50–85% and adherence, respectively. 79 (33%) and 36 (15%) of the subjects experienced a persistent 25% decline in eGFR or allograft loss and 50% decline in eGFR or allograft loss during follow-up. Adherence was not associated with acute rejection or 25% decline or 50% decline in eGFR. In the adjusted and unadjusted model, adherence and black race were not associated with change in eGFR over time. Conclusions Non-adherence with a single immunosuppressive medication, was not associated with kidney allograft outcomes. PMID:20977496

  13. Discrepancies between beliefs and behavior: a prospective study into immunosuppressive medication adherence after kidney transplantation.

    Science.gov (United States)

    Massey, Emma K; Tielen, Mirjam; Laging, Mirjam; Timman, Reinier; Beck, Denise K; Khemai, Roshni; van Gelder, Teun; Weimar, Willem

    2015-02-01

    Nonadherence to immunosuppressive medication after kidney transplantation is a behavioral issue and as such it is important to understand the psychological factors that influence this behavior. The aim of this study was to investigate the extent to which goal cognitions, illness perceptions, and treatment beliefs were related to changes in self-reported immunosuppressive medication adherence up to 18 months after transplantation. Interviews were conducted with patients in the outpatient clinic 6 weeks (T1; n=113), 6 months (T2; n=106), and 18 months (T3; n=84) after transplantation. Self-reported adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale Interview. Psychological concepts were measured using the Brief Illness Perceptions Questionnaire, Beliefs about Medicines Questionnaire, and questions on the importance of adherence as a personal goal, conflict with other goals, and self-efficacy for goal attainment. Nonadherence significantly increased over time to 31% at T3. Perceived necessity of medication, perceived impact of transplant on life (consequences) and emotional response to transplantation significantly decreased over time. Participants who reported low importance of medication adherence as a personal goal were more likely to become nonadherent over time. Illness perceptions can be described as functional and supportive of adherence which is inconsistent with the pervasive and increasing nonadherence observed. There appears therefore to be a discrepancy between beliefs about adherence and actual behavior. Promoting (intrinsic) motivation for adherence goals and exploring the relative importance in comparison to other personal goals is a potential target for interventions.

  14. Electronically measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation.

    Science.gov (United States)

    Israni, Ajay K; Weng, Francis L; Cen, Ye-Ying; Joffe, Marshall; Kamoun, Malek; Feldman, Harold I

    2011-01-01

    Non-adherence with immunosuppressive medications can result in allograft rejection and eventually allograft loss. In a racially diverse population, we utilized microelectronic cap monitors to determine the association of adherence with a single immunosuppressive medication and kidney allograft outcomes post-transplantation. This prospective cohort study enrolled 243 patients from eight transplant centers to provide adherence and kidney allograft outcomes data. To determine the association of adherence with change in estimated glomerular filtration rate (eGFR), we fit mixed effects models with the outcome being change in eGFR over time. We also fit Cox proportional hazards models to determine the association of adherence with time to persistent 25% and 50% decline in eGFR. The distribution of adherence post-transplant was as follows: 164 (68%), 49 (20%), and 30 (12%) had >85-100%, 50-85%, and adherence, respectively. Seventy-nine (33%) and 36 (15%) of the subjects experienced a persistent 25% decline in eGFR or allograft loss and 50% decline in eGFR or allograft loss during follow-up. Adherence was not associated with acute rejection or 25% decline or 50% decline in eGFR. In the adjusted and unadjusted model, adherence and black race were not associated with change in eGFR over time. Non-adherence with a single immunosuppressive medication was not associated with kidney allograft outcomes. © 2010 John Wiley & Sons A/S.

  15. In Silico Characterization and Structural Modeling of Dermacentor andersoni p36 Immunosuppressive Protein

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    Martin Omulindi Oyugi

    2018-01-01

    Full Text Available Ticks cause approximately $17–19 billion economic losses to the livestock industry globally. Development of recombinant antitick vaccine is greatly hindered by insufficient knowledge and understanding of proteins expressed by ticks. Ticks secrete immunosuppressant proteins that modulate the host’s immune system during blood feeding; these molecules could be a target for antivector vaccine development. Recombinant p36, a 36 kDa immunosuppressor from the saliva of female Dermacentor andersoni, suppresses T-lymphocytes proliferation in vitro. To identify potential unique structural and dynamic properties responsible for the immunosuppressive function of p36 proteins, this study utilized bioinformatic tool to characterize and model structure of D. andersoni p36 protein. Evaluation of p36 protein family as suitable vaccine antigens predicted a p36 homolog in Rhipicephalus appendiculatus, the tick vector of East Coast fever, with an antigenicity score of 0.7701 that compares well with that of Bm86 (0.7681, the protein antigen that constitute commercial tick vaccine Tickgard™. Ab initio modeling of the D. andersoni p36 protein yielded a 3D structure that predicted conserved antigenic region, which has potential of binding immunomodulating ligands including glycerol and lactose, found located within exposed loop, suggesting a likely role in immunosuppressive function of tick p36 proteins. Laboratory confirmation of these preliminary results is necessary in future studies.

  16. The role of basiliximab in the evolving renal transplantation immunosuppression protocol

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    Paola Salis

    2008-06-01

    Full Text Available Paola Salis, Chiara Caccamo, Roberto Verzaro, Salvatore Gruttadauria, Mary ArteroDivision of Nephrology and Division of Abdominal Transplantation, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, ItalyAbstract: Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2 receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR inhibitors for calcineurin inhibitors.Keywords: basiliximab, renal transplantation, IL-2 receptor antagonists, induction, immunosuppression, corticosteroids, calcineurin inhibitors

  17. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  18. CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    International Nuclear Information System (INIS)

    Wang, Ding; Chen, Ke; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying

    2010-01-01

    Here, the effect of CD14 + monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-γ (IFN-γ) secretion capacities of CD4 + and CD8 + T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E 2 (PGE 2 ) as an important soluble mediator. CD14 + monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1β, either exogenously added or produced by CD14 + monocytes in culture, could trigger expression of high levels of PGE 2 by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE 2 expression, but also reversed the promotional effect of CD14 + monocytes and partially restored CD4 + and CD8 + T cell proliferation and IFN-γ secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  19. The regulatory role of immunosuppressants on immune abnormalities in acute pancreatitis.

    Science.gov (United States)

    Duan, Ligeng; Ma, Yu; Chi, Junlin; Wang, Xu; Wesley, Alexander J; Chen, Xiaoli

    2014-03-01

    The uncontrolled progression of the inflammatory cascade is the main cause underlying the development of multiple organ dysfunction syndrome (MODS) in acute pancreatitis. In this study, we investigated the effects of several immunosuppressants on mitigating the systemic inflammatory reaction syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) associated with acute pancreatitis. A total of 93 male Sprague Dawley rats were divided into 5 groups: group 1 was the sham group and group 2 underwent laparoscopic intrapancreatic duct injection of sodium taurocholate to induce pancreatitis. The remaining 3 groups were the same as group 2, with the addition of methylprednisolone, cyclophosphamide or methotrexate treatment (metastab, CTX or MTX groups, respectively). Following establishment of the acute pancreatitis model, the serum levels of inflammatory and anti-inflammatory cytokines in groups 2, 3, 4 and 5 were found to be significantly elevated. Following immunosuppressant administration, the levels of all inflammatory and anti-inflammatory cytokines investigated in groups 3, 4 and 5 were decreased compared to those in group 2. The pancreatic amylase levels and pancreatic wet weight (PWW) were also decreased in groups 3, 4 and 5 compared to those in group 2. Therefore, immunosuppressants may reduce inflammation-related cytokine levels in acute pancreatitis and relieve disease progression.

  20. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

    LENUS (Irish Health Repository)

    Olaitan, Oyedolamu K

    2010-02-01

    To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.

  1. Immunosuppression and temporary skin transplantation in the treatment of massive third degree burns.

    Science.gov (United States)

    Burke, J F; Quinby, W C; Bondoc, C C; Cosimi, A B; Russell, P S; Szyfelbein, S K

    1975-01-01

    A method of burn treatment (immunosuppression and temporary skin transplantation) for patients suffering from massive third degree burns is evaluated. The method is based on the prompt excision of all dead tissue (burn eschar) and immediate closure of the wound by skin grafts. Total wound closure is achieved before bacterial infection or organ failure takes place by carrying out all initial excision and grafting procedures within the first ten days post burn and supplementing the limited amount of autograft with allograft. Continuous wound closure is maintained for up to 50 days through immunosuppression. Both azathioprine and ATG have been used but ATG is preferred. During the period of immunosuppression, allograft is stepwise excised and replaced with autograft donor sites regenerate for recropping. Bacterial complications are minimized by housing the patient in the protected environment of the Bacteria Controlled Nursing Unit. Intensive protein and calorie alimentation are provided, and 0.5% aqueous AgNO3 dressings are used. A swinging febrile illness has been associated with large areas of allograft rejection. Eleven children have been treated and seven have been returned to normal, productive schooling. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:809014

  2. [Treatment with immunosuppressive and biologic drugs of pregnant women with systemic rheumatic or autoimmune disease].

    Science.gov (United States)

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel

    2016-10-21

    Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jennifer Wang

    2015-01-01

    Full Text Available Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy.

  4. Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

    Directory of Open Access Journals (Sweden)

    Franco-Molina MA

    2016-01-01

    and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment. Keywords: melanoma, Foxp3, cancer, T-regulatory cells

  5. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial.

    Science.gov (United States)

    Khanna, Reena; Bressler, Brian; Levesque, Barrett G; Zou, Guangyong; Stitt, Larry W; Greenberg, Gordon R; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J; Donner, Allan; Vandervoort, Margaret K; Morris, Joan C; Feagan, Brian G

    2015-11-07

    Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤ 4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95

  6. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A; Voskuyl, A E; Vervloet, M G; Bijl, M; de Sévaux, R G L; Berger, S P; Derksen, R H W M; Berden, J H M

    2012-01-01

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  7. Recent advances in cell-based therapy for Parkinson disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Cooper, Oliver; Vinuela, Angel

    2008-01-01

    In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression...

  8. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis.

    NARCIS (Netherlands)

    Tellingen, A. van; Voskuyl, A.E.; Vervloet, M.G.; Bijl, M. van der; Sevaux, R.G.L. de; Berger, S.P.; Derksen, R.H.W.M.; Berden, J.H.M.

    2012-01-01

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  9. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  10. CHANGES IN MOUSE CIRULATING LEUKOCYTE NUMBERS IN C57BL/6 MICE IMMUNOSUPPRESSED FOR CRYPTOSPORIDIUM PARVUM OOCYST PRODUCTION

    Science.gov (United States)

    The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised Nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone - tetracy...

  11. Risks vs benefits of glatiramer acetate: a changing perspective as new therapies emerge for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kenneth P Johnson

    2010-04-01

    Full Text Available Kenneth P JohnsonMaryland Center for MS, Baltimore, Maryland, USAAbstract: An understanding of the risks, benefits, and relative value of glatiramer acetate (GA in multiple sclerosis (MS has been evolving based on recently completed head-to-head studies: REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease; BEYOND (Betaseron Efficacy Yielding Outcomes of a New Dose; and BECOME (BEtaseron vs COpaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3-Tesla MRI Endpoints. Outcomes in the primary endpoints of these trials showed no significant differences between GA and high-dose beta-interferons (IFNβs. Results of the PreCISe (Early GA Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis [CDMS] in Subjects Presenting With a Clinically Isolated Syndrome [CIS] trial led to the US Food and Drug Administration approval of GA in patients with a CIS. Furthermore, the ongoing follow-up study to the original pivotal GA trial, now extending beyond 15 years, continues to support the safety of GA. Currently, GA and IFNβs are no longer the only immunomodulators available for MS. Introduction of the monoclonal antibody, natalizumab (Tysabri®; Biogen Idec, Inc., Cambridge, MA, USA provides an alternative immunomodulator for MS and has changed the therapeutic landscape dramatically. However, the rare but serious cases of progressive multifocal leukoencephalopathy that have occurred with natalizumab have raised concerns among clinicians and patients about using this agent and some of the emerging agents. The potential risks and benefits of the emerging therapies (cladribine, alemtuzumab, rituximab, fingolimod, laquinimod, teriflunomide, and dimethyl fumarate based on phase II/III trials, as well as their use for indications other than MS, will be presented. This review provides available data on GA, natalizumab, and the emerging agents to support new developments in our understanding of GA and how its long-standing role as a

  12. Why do Patients Forget to Take Immunosuppression Medications and Miss Appointments: Can a Mobile Phone App Help?

    OpenAIRE

    Israni, Ajay; Dean, Carl; Kasel, Brian; Berndt, Lisa; Wildebush, Winston; Wang, C Jason

    2016-01-01

    Background Kidney transplant recipients must adhere to their immunosuppressive medication regimen. However, non-adherence remains a major problem. Objective The aim of this paper is to determine how kidney transplant recipients remember to take their medications, and assess their perception and beliefs about adherence to immunosuppressive medications and barriers to medication adherence. In addition, we aim to assess perception and beliefs about willingness to use a hypothetical, mobile phone...

  13. Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bryony Jenkins

    2016-12-01

    Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

  14. Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bryony Jenkins

    2017-02-01

    Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of pMHC formation or TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

  15. Role of Cyclooxygenase-2 Pathway in Creating an Immunosuppressive Microenvironment and in Initiation and Progression of Wilms' Tumor

    Directory of Open Access Journals (Sweden)

    Paramahamsa Maturu

    2017-03-01

    Full Text Available Wilms' tumors (WT, which accountfor 6% of all childhood cancers, arise from dysregulated differentiation of nephrogenic progenitor cells from embryonic kidneys. Though there is an improvement in the prognosis of WT, still 10% of patients with WT die due to recurrence. Thus more effective treatment approaches are necessary. We previously characterized the inflammatory microenvironment in human WT and observed the robust expression of COX-2. The aim of this study was to extend our studies to analyze the role of COX-2 pathway components in WT progression using a mouse model of WT. Herein, COX-2 pathway components such as COX-2, HIF1-α, p-ERK1/2, and p-STAT3 were upregulated in mouse and human tumor tissues. In our RPPA analysis, COX-2 was up-regulated in M15 cells after Wt1 gene was knocked down. Flow cytometry analysis showed the increased infiltration of immune suppressive inflammatory cells such as pDC's and Treg cells in tumors. The chemotactic chemokines responsible for the infiltration of these cells were also induced in CCR5 and CXCR4 dependent manner respectively. The immunosuppressive cytokines IL-10, TGF-β, and TNF-α were also up-regulated. Furthermore, more pronounced Th2 and Treg induced cytokine response was observed than Th1 response in tumors. Basing on all these evidences it is speculated that COX-2 pathway may be a beneficial target for the treatment of WT. It may be most effective as an adjuvant therapy together with other inhibitors. Thus, our current study provides a good rationale for initiating animal studies to confirm the efficacy of COX-2 inhibitors in decreasing tumor cell growth in vivo.

  16. Risk of fracture in adults on renal replacement therapy

    DEFF Research Database (Denmark)

    Hansen, Ditte; Olesen, Jonas B; Gislason, Gunnar H

    2016-01-01

    BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and ex....... Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy....

  17. Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Stefan Jenkins

    2013-12-01

    Full Text Available Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP and aqueous normal phase (ANP chromatographic separations, as well as electrospray ionization (ESI and atmospheric pressure chemical ionization (APCI sources for detection in both ion polarities. Unsupervised principle component analysis (PCA and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published

  18. The use of irradiated food for immuno-suppressed hospital patients

    International Nuclear Information System (INIS)

    Pryke, D.C.

    1994-01-01

    The treatment of leukaemia and other forms of haematological malignancies involves destruction of the bone marrow followed by bone-marrow transplant. This results in patients becoming severely immuno-suppressed. Other diseases result in a similar condition, most notably Acquired Immuno-Deficiency Syndrome (AIDS). Irradiation using radioactive sources or machines has been proposed as a method for preparing foods for immuno-suppressed patients and other high risk groups. Doses of around 30 kGy ensure a total sterility whilst a dose of 10 kGy (the recommended maximum for food available to the general public) results in a significant reduction in the number of pathogenic microorganisms. Irradiation has a number of advantages over other processing methods, in particular that flavour, texture and nutritional changes are limited. This is important as patients are often in a compromised state and need clinical assistance in returning to normal eating habits. In recognition of the potential of irradiated foods for hospital patients this use has been specifically exempted from regulatory control in the UK. This paper reviews the experience in the UK of irradiation-sterilized foods in hospitals. It was found that for practical reasons use is currently restricted. The future prospects for food irradiated at non-sterilized doses are also considered. It is concluded that as well as providing greater choice for consumers (high risk and the general public as a whole) irradiated foods could extend and improved the diets of immuno-suppressed hospital patients; this could be an important factor in recovery. (author)

  19. Single mutations in the transmembrane envelope protein abrogate the immunosuppressive property of HIV-1

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    Morozov Vladimir A

    2012-08-01

    Full Text Available Abstract Background The mechanism by which HIV-1 induces AIDS is still unknown. Previously, synthetic peptides corresponding to the conserved immunosuppressive (isu domain in gp41 of HIV-1 had been shown to inhibit proliferation and to modulate cytokine expression of immune cells. The question is, whether the viral gp41 can do the same. Results We show for the first time that two trimeric forms of glycosylated gp41 released from transfected human cells modulated expression of cytokines and other genes in human PBMCs in the same manner, but at least seven hundred-fold stronger compared to that induced by the isu peptide. Single amino acid substitutions in the isu domain of gp41 introduced by site-directed mutagenesis abrogated this property. Furthermore, replication-competent HIV-1 with a mutation in the isu domain of gp41 did not modulate the cytokine expression, while wild-type virus did. Interestingly, most of the abrogating mutations were not reported in viral sequences derived from infected individuals, suggesting that mutated non-immunosuppressive viruses were eliminated by immune responses. Finally, immunisation of rats with gp41 mutated in the isu domain resulted in increased antibody responses compared with the non-mutated gp41. These results show that non-mutated gp41 is immunosuppressive in immunisation experiments, i.e. in vivo, and this has implications for the vaccine development. Conclusions These findings indicate that the isu domain of gp41 modulates cytokine expression in vitro and suppresses antibody response in vivo and therefore may contribute to the virus induced immunodeficiency.

  20. Immunosuppressive effects of Pteridium aquilinum enhance susceptibility to urethane-induced lung carcinogenesis.

    Science.gov (United States)

    Caniceiro, Beatriz D; Latorre, Andreia O; Fukumasu, Heidge; Sanches, Daniel S; Haraguchi, Mitsue; Górniak, Silvana L

    2015-01-01

    Pteridium aquilinum (bracken fern), one of the most important toxic plants in the world, contains the toxic norsequiterpene ptaquiloside that induces cancers in humans and farm animals. Previous studies in the laboratory demonstrated immunotoxic effects produced by ptaquiloside, which are characterized by suppression of natural killer (NK) cell activity (i.e. cytotoxicity and interferon [IFN]-γ production). However, it is unknown whether these immunosuppressive effects could contribute to carcinogenesis in situ in general because of the important function of NK cells in innate killing of tumor cells. This study assessed the impact of P. aquilinum-induced immunosuppression on urethane-induced lung cancer in C57BL/6 mice. Adult mice were treated with an extract of P. aquilinum (30 g/kg/day) by gavage once daily for 14 days, followed by gavage (5 days/week) during an 11-week period that was accompanied by treatment with urethane (1 g/kg) via once-weekly intraperitoneal injection; 20 weeks after the end of the treatment period, all lungs were evaluated. The results indicated there was a significant increase in lung nodule number as well as in multiplicity of lesions in mice treated with both P. aquilinum and urethane (PU group) compared to values in mice treated only with the urethane (U group). In addition, histologic evaluation revealed a 76% increase in the rate of lung adenomas and a 41% increase in rate of bronchiolization of alveoli in the mice from the PU group compared to levels seen in mice within the U group. Taken together, the results here show for the first time that immunosuppressive effects of P. aquilinum could increase the risk of cancer formation in exposed hosts.

  1. Association of Marek's Disease induced immunosuppression with activation of a novel regulatory T cells in chickens.

    Directory of Open Access Journals (Sweden)

    Angila Gurung

    2017-12-01

    Full Text Available Marek's Disease Virus (MDV is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT, fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour

  2. [Correlation of the manifestations of tuberculosis and the degree of immunosuppression in patients with HIV].

    Science.gov (United States)

    Kouassi, B; N'Gom, A; Horo, K; Godé, C; Ahui, B; Emvoudou, N M L; Koffi, N; Anon, J C; Konaté, K F; Itchi, M; Koffi, M O; Ano, A; Manewa, S F; Gro Bi, A; Aka-Danguy, E; Gnazé, A; Touré, K

    2013-09-01

    Correlation of the manifestations of tuberculosis and the degree of immunosuppression in patients with HIV. The advent of HIV has contributed to the increase in the number of people with tuberculosis. The clinical and paraclinical of TB/HIV co-infected are polymorphic and function of immune status. To determines the clinical and paraclinical characteristics of TB related to different levels of CD4 lymphocytes. A retrospective case series based on analysis of 450 patients with both TB/HIV co-infections. It focused on the records of patients with pulmonary smear-positive (TPM +) with a positive HIV status. The effect of immunosuppression was analyzed in groups based on the CD4 count (350/mm(3)), in a chronological fashion from April to September 2010 until there were 150 patients in each CD4 group. Among the 450 patients, 71.1% were between 25 and 45years old. The clinical signs were more significant as the level of CD4 fell. The clinical signs were predominantly fever (93%) and weight loss (62.7%). Pulmonary cavitation (59.3%), infiltrates (38.7%) and the location of the lesions at the lung apex (72%) were more common in the third group patients. By contrast, extra pulmonary lesions (mediastinal lymphadenopathy, pleurisy) and normal x-ray (9.3%) were more frequent in patients of the first group. The scarcity of cavitations (22.3% compared to 59.3% CD4>350) and the increase in associated lesions became more marked if patients were immunocompromised. Hematologic, hepatic, renal disorders were more frequent and severe in the most immunocompromised patient group. HIV-associated tuberculosis has an atypical clinical, radiological, biological presentation and is more severe when there is significant immunosuppression. Copyright © 2013. Published by Elsevier Masson SAS.

  3. A novel peptide mimotope identified as a potential immunosuppressive vaccine for organ transplantation.

    Science.gov (United States)

    Chiang, Kuei-Chen; Shimada, Yayoi; Nakano, Toshiaki; Lai, Chia-Yun; Hsu, Li-Wen; Goto, Shigeru; Ohmori, Naoya; Mori, Kenji; Miyagi, Takamitsu; Kawamoto, Seiji; Ono, Kazuhisa; Chen, Chao-Long; Goto, Takeshi; Sato, Shuji

    2009-04-01

    We reported that anti-histone H1 autoantibody is one of the main immunosuppressive factors in serum that is induced after orthotopic liver transplantation in a rat tolerogenic model. We generated a novel anti-histone H1 IgM mAb produced by hybridoma 16G9 (16G9 mAb) that shows MLR-inhibitory activity. Identification of a functional epitope responsible for the immunosuppressive activity of 16G9 mAb may lead to the establishment of a novel therapeutic strategy. We used a combinatorial phage display peptide library to screen for peptides that bind to 16G9 mAb. Consequently, two peptides that bind to 16G9 mAb, SSV and LPQ, were selected from the library. The binding of 16G9 mAb to histone H1 was inhibited by SSV. SSV was recognized by rat tolerogenic post-orthotopic liver transplantation serum and the binding to SSV was inhibited by histone H1. Mice were immunized with keyhole limpet hemocyanin-conjugated SSV and LPQ. Abs induced by SSV immunization inhibited Con A-stimulated splenocyte proliferation, and the inhibition was neutralized by preincubation with SSV. Splenocytes stimulated by anti-CD3 Ab were inhibited by SSV-induced Abs using CFSE labeling. SSV immunization in rats before heterotopic heart transplantation resulted in significant prolonged allograft survival. These findings suggested that SSV is a functional histone H1-binding epitope for 16G9 mAb. SSV is capable of determining serum immunoreactivity against histone H1 as an index marker for tolerance. The inhibitory activity of SSV-induced Abs on blast cell proliferation and the prolonged graft survival that results from SSV immunization imply a potential for the development of an immunosuppressive vaccine.

  4. CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ding, E-mail: qqhewd@gmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Chen, Ke, E-mail: chenke_59@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Du, Wei Ting, E-mail: duwtpumc@yahoo.com.cn [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); Han, Zhi-Bo, E-mail: zhibohan@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Ren, He, E-mail: knifesharp2000@hotmail.com [National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, TEDA, Tianjin (China); Chi, Ying, E-mail: caizhuying@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); and others

    2010-09-10

    Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  5. Effect of ginseng polysaccharides on NK cell cytotoxicity in immunosuppressed mice.

    Science.gov (United States)

    Sun, Yaoyao; Guo, Mofei; Feng, Yuanjie; Zheng, Huifang; Lei, Ping; Ma, Xiande; Han, Xiaowei; Guan, Hongquan; Hou, Diandong

    2016-12-01

    The aim of the present study was to investigate the effects of Ginseng polysaccharides (GPS) on natural killer (NK) cell cytotoxicity in immunosuppressed mice. Cyclophosphamide (Cy) was used to construct an immunosuppressed mouse model. The mice in each group were submitted to gavages with 200 or 400 mg/kg GPS every day for 10 days. Magnetic-activated cell sorting was used to isolate spleen NK cells, and the NK cell cytotoxicity, blood distribution, expression levels of perforin and granzyme, and the mRNA expression levels of interferon (IFN)-γ were detected. Compared with the normal control group, the cytotoxicity and proportion of NK cells in the blood, and the expression levels of perforin, granzyme and IFN-γ mRNA in the Cy model group were significantly reduced (Pcytotoxicity and proportion of NK cells in the whole blood, and the expression levels of perforin and granzyme in the NK cells in the Cy + low-dose GPS and Cy + high-dose GPS groups were significantly increased (P0.05). Compared with the normal control group, the cytotoxicity and proportion of NK cells in the whole blood, and the expression levels of perforin in the Cy + low-dose GPS and the Cy + high-dose GPS groups were significantly lower (P0.05). These results suggested that GPS promotes NK cell cytotoxicity in immunosuppressed mice by increasing the number of NK cells in the whole blood and upregulating the expression of perforin and granzyme. Thus, the present study investigated the molecular mechanism underlying NK cell activation by GPS, the research showed that GPS have a wide application prospects in the treatment of cancer and immunodeficiency diseases.

  6. Gastrointestinal disorders after immunosuppression: an experimental model to evaluate the influence of monotherapy on motility parameters.

    Science.gov (United States)

    Dall'Agnol, Denize Jussara Rupolo; Corá, Luciana Aparecida; Teixeira, Maria do Carmo Borges; de Lima, Maysa Bruno; Gama, Loyane Almeida; Miranda, José Ricardo de Arruda; Américo, Madileine Francely

    2017-08-01

    What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg -1  day -1 considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min -1 ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs

  7. Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression

    International Nuclear Information System (INIS)

    Blum, J.E.; de Silva, S.M.; Rachman, D.B.; Order, S.E.

    1988-01-01

    Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity

  8. Venom-Induced Immunosuppression: An Overview of Hemocyte-Mediated Responses

    Directory of Open Access Journals (Sweden)

    Aylin Er

    2011-01-01

    Full Text Available Parasitic wasps are important natural enemies of several insect pests. They use a variety of methods to modulate their insect host for their progeny to develop. For example, the female wasp needs to avoid or suppress the host immune responses by introducing venom with or without virus like particles and/or polydnaviruses. The aim of this paper is to provide a synthesis of current knowledge regarding the immunosuppression of host immunity with venom in parasitoids that are devoid of symbiotic viruses. Special emphasis is given through disabling host hemocytes by venom of the endoparasitoid Pimpla turionellae (Hymenoptera: Ichneumonidae with comparisons of venoms from other parasitoid species.

  9. The role of urocanic acid in UV-induced immunosuppression: recent advances (1992-1994)

    International Nuclear Information System (INIS)

    Norval, M.

    1995-01-01

    Cis-urocanic acid (UCA), formed in the epidermis by UV irradiation of trans-UCa, has been implicated as a mediator of the immunosuppression induced by UV exposure of the skin. This review covers recent work in which the wavelength dependence of cis-UCa formation, the interaction of UCA isomers with DNA, the effects of UCA isomers on the immune system and their interaction with histamine are examined. Results are frequently conflicting, particularly when considering the possible mode of action of cis-UCA but, overall, a multifaceted role for UCA in immunomodulation by UV radiation is substantiated. (author)

  10. VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection.

    Science.gov (United States)

    Gebremariam, Teclegiorgis; Wiederhold, Nathan P; Fothergill, Annette W; Garvey, Edward P; Hoekstra, William J; Schotzinger, Robert J; Patterson, Thomas F; Filler, Scott G; Ibrahim, Ashraf S

    2015-12-01

    We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests

    DEFF Research Database (Denmark)

    Hammer, J H; Nielsen, Hans Jørgen; Moesgaard, F

    1992-01-01

    The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four times....... In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days....

  12. Future therapies for pemphigus vulgaris: Rituximab and beyond.

    Science.gov (United States)

    Huang, Amy; Madan, Raman K; Levitt, Jacob

    2016-04-01

    The conventional treatment for patients with pemphigus vulgaris (PV) centers on global immunosuppression, such as the use of steroids and other immunosuppressive drugs, to decrease titers of antidesmoglein autoantibodies responsible for the acantholytic blisters. Global immunosuppressants, however, cause serious side effects. The emergence of anti-CD20 biologic medications, such as rituximab, as an adjunct to conventional therapy has shifted the focus to targeted destruction of autoimmune B cells. Next-generation biologic medications with improved modes of delivery, pharmacology, and side effect profiles are constantly being developed, adding to the diversity of options for PV treatment. We review promising monoclonal antibodies, including veltuzumab, obinutuzumab (GA-101), ofatumumab, ocaratuzumab (AME-133v), PRO131921, and belimumab. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Proton therapy

    Science.gov (United States)

    Proton beam therapy; Cancer - proton therapy; Radiation therapy - proton therapy; Prostate cancer - proton therapy ... that use x-rays to destroy cancer cells, proton therapy uses a beam of special particles called ...

  14. The central effect of biological Amines on immunosuppressive effect of restraint stress in rat

    Directory of Open Access Journals (Sweden)

    Zeraati F

    2000-10-01

    Full Text Available The effects of some histaminergic agents were evaluated on stress- induced immunosuppression in immunized nale rats. In rat immunized with sheep red blood cells ( SRBCs. Restraint stress (RS prevented the booster-induced rise in anti-SRBC antibody titre and cell immunity response. Intracerebroventicular (I.C>V injection of histamine (150 µg/rat induced a similar effect with RS. Pretreatment with chlorpheniramine (50 µg/rat reduced the inhibitory effect of Ras on immune function. Also histamine could inhibit the effect of RS on immune function. Also histamine could inhibitory the effect of chlorpheniramine when injected simultaneously. Pretreatment with ranidine (10 µg/rat had not a significant effect. Serotonin (3 µg/rat and dopamine (0.2 µg/rat could reverse the effects of chlorpheniromine when injected with chlorpheniramine (P<0.05. Epinephrine (0.2 µg/rat had not a significant effect. The results indicate that histamine mediates the immunosuppression of restraint stress by influencing the histamine H1 receptor in the brain and this effects of histamine may be modulated by serotoninergic and dopaminergic system.

  15. Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

    Science.gov (United States)

    Barthélémy, Inès; Uriarte, Ane; Drougard, Carole; Unterfinger, Yves; Thibaud, Jean-Laurent; Blot, Stéphane

    2012-01-01

    The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease. PMID:23185260

  16. Mesenchymal stem cell infusion on skin wound healing of dexamethasone immunosuppressed wistar rats

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    Betânia Souza Monteiro

    Full Text Available ABSTRACT: To evaluate the therapeutic contribution of MSC intravenous infusion to surgical wound healing in dexamethasone-immunosuppressed rats, thirty-five rats were randomly divided into 2 groups: in the Control Group (CG, five rats received normal saline as 0.2ml subcutaneous (SC injections every 24 hours, for 30 consecutive days and, in the Dexamethasone Group (DG, 30 rats were given 0.2mL subcutaneous dexamethasone (0.1mg kg-1 every 24 hours, for 30 consecutive days. After 30 days, all rats underwent surgery to create an experimental skin wound. The 30 animals of the DG group were divided into two equal groups, which received different treatments: the dexamethasone group (DG received a single application of 0.5ml normal saline, via the intravenous route (IV, 48 hours after wound creation; and the Mesenchymal Stem Cells Dexamethasone group (MSCDG received MSC transplantation at a concentration of 9x106 cells in a single IV application, 48 hours after wound creation. The surgical wounds of CG rats closed on average 14.75 days after creation and DG rats had wounds closed within 22 days; whereas, the surgical wounds of MSCDG rats were closed in 14 days. MSC infusion in dexamethasone-immunosuppressed patients contributed positively to epithelial healing in less time.

  17. Oral candidiasis in immunosuppressed children and young adults after liver or kidney transplantation.

    Science.gov (United States)

    Olczak-Kowalczyk, Dorota; Pawłowska, Joanna; Garczewska, Barbara; Smirska, Ewa; Grenda, Ryszard; Syczewska, Małgorzata; Kowalczyk, Wojciech

    2010-01-01

    Candidiasis is an infectious complication in organ transplant recipients resulting from the patients' immunodeficiency and virulence of fungi pathogens. The purpose of this study was to evaluate the frequency of Candida spp. and identify their presence in the oral lesions of graft recipients. This study included 185 patients, 1.5 to 25.2 years of age (mean = 13.1 +/- 4.2 years) who were receiving combined immunosuppression treatment after kidney or liver transplantation and 70 control subjects. Evaluation included clinical oral examination, mycology, and statistical analysis. Candida spp. colonies were found in the oral mucosa of 63 (34%) graft recipients and in 19 (27%) control subjects. Candida albicans was the most prevalent species. This study showed that, regardless of the type of the organ transplant and immunosuppression, frequent, regular oral follow-up and mycologic tests are recommended. Diagnosing increased density of Candida spp. colonies in the oral cavity will help initiate early antifungal treatment. Candida spp. prevalence in the oral cavity in transplant recipients was higher than in immunocompetent control subjects. Kidney or liver transplantation predisposes one to the development of an increased density of Candida spp. colonies.

  18. Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses

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    Hsin-Chun Chen

    2016-08-01

    Full Text Available Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC and gas chromatography/mass spectrometry (GC/MS with direct injection (DI/GC or headspace-solid phase microextraction (HS-SPME/GC. In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial. An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases.

  19. Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study

    Directory of Open Access Journals (Sweden)

    Daniela Cristina Sampaio de Brito

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE : Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. DESIGN AND SETTING : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. METHODS :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. RESULTS : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P < 0.05 and had a marginal trend toward significance with more advanced phases of stress (OR 4.7; CI: 0.99-22.51; P = 0.053. CONCLUSION :Stress and coping strategies may have implications for understanding and managing nonadherent behavior among transplantation patients and should be considered among the strategies for reducing nonadherence.

  20. Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study.

    Science.gov (United States)

    Brito, Daniela Cristina Sampaio de; Marsicano, Elisa Oliveira; Grincenkov, Fabiane Rossi Dos Santos; Colugnati, Fernando Antônio Basile; Lucchetti, Giancarlo; Sanders-Pinheiro, Helady

    2016-01-01

    : Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P transplantation patients and should be considered among the strategies for reducing nonadherence.

  1. Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma patients.

    Science.gov (United States)

    Torrance, Hew Dt; Brohi, Karim; Pearse, Rupert M; Mein, Charles A; Wozniak, Eva; Prowle, John R; Hinds, Charles J; OʼDwyer, Michael J

    2015-04-01

    To explore the hypothesis that blood transfusion contributes to an immunosuppressed phenotype in severely injured patients. Despite trauma patients using disproportionately large quantities of blood and blood products, the immunomodulatory effects of blood transfusion in this group are inadequately described. A total of 112 ventilated polytrauma patients were recruited. Messenger RNA (mRNA) was extracted from PAXGene tubes collected within 2 hours of the trauma, at 24 hours, and at 72 hours. T-helper cell subtype specific cytokines and transcription factors were quantified using real-time polymerase chain reaction. Median injury severity score was 29. Blood transfusion was administered to 27 (24%) patients before the 2-hour sampling point. Transfusion was associated with a greater immediate rise in IL-10 (P = 0.003) and IL-27 (P = 0.04) mRNA levels. Blood products were transfused in 72 (64%) patients within the first 24 hours. There was an association between transfusion at 24 hours and higher IL-10 (P transfused. Multiple regression models confirmed that the transfusion of blood products was independently associated with altered patterns of gene expression. Blood stream infections occur in 15 (20.8%) of those transfused in the first 24 hours, compared with 1 patient (2.5%) not transfused (OR = 10.3 [1.3-81], P = 0.008). The primarily immunosuppressive inflammatory response to polytrauma may be exacerbated by the transfusion of blood products. Furthermore, transfusion was associated with an increased susceptibility to nosocomial infections.

  2. The Release of Immunosuppressive Factor(s in Young Males Following Exercise

    Directory of Open Access Journals (Sweden)

    Julien S. Baker

    2012-05-01

    Full Text Available It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th–9th min post-exercise eluates (P < 0.05. Such findings suggest that intense eccentric type exercise may lead to generation of immunosuppressive factor(s in young males.

  3. Thymoglobulin induction in heart transplantation: patient selection and implications for maintenance immunosuppression

    Science.gov (United States)

    Zuckermann, Andreas; Schulz, Uwe; Deuse, Tobias; Ruhpawar, Arjang; Schmitto, Jan D; Beiras-Fernandez, Andres; Hirt, Stephan; Schweiger, Martin; Kopp-Fernandes, Laurenz; Barten, Markus J

    2015-01-01

    Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor-specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence-based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics. PMID:25363471

  4. Medicare immunosuppressant coverage and access to kidney transplantation: a retrospective national cohort study

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    Grubbs Vanessa

    2012-08-01

    Full Text Available Abstract Background In December 2000, Medicare eliminated time limitations in immunosuppressant coverage after kidney transplant for beneficiaries age ≥65 and those who were disabled. This change did not apply to younger non-disabled beneficiaries who qualified for Medicare only because of their end-stage renal disease (ESRD. We sought to examine access to waitlisting for kidney transplantation in a cohort spanning this policy change. Methods This was a retrospective cohort analysis of 241,150 Medicare beneficiaries in the United States Renal Data System who initiated chronic dialysis between 1/1/96 and 11/30/03. We fit interrupted time series Cox proportional hazard models to compare access to kidney transplant waitlist within 12 months of initiating chronic dialysis by age/disability status, accounting for secular trends. Results Beneficiaries age Conclusions The most recent extension in Medicare immunosuppressant coverage appears to have had little impact on the already increasing access to waitlisting among ≥65/ disabled beneficiaries eligible for the benefit but may have decreased access for younger, non-disabled beneficiaries who were not. The potential ramifications of policies on candidacy appeal for access to kidney transplantation should be considered.

  5. Feasibility of ionizing radiation decontamination of ready to eat fresh vegetable salads for immunosuppressed patients

    International Nuclear Information System (INIS)

    Horak, Celina I.; Narvaiz, Patricia; Kairiyama, Eulogia; Adeil Pietranera, Maria S.; Gimenez, Palmira; Gronostajsky, D.

    2003-01-01

    In the last years consumer trends have increased for fresh like and minimally processed foods. Also, foods are frequently requested without or reduced chemical preservatives. Minimally processed foods have a limited shelf life and mainly rely on HACCP and refrigeration for preservation. However, over the last years, the detection of food borne illness outbreaks associated with fresh vegetables and fruits has increased. This is possible because these product characteristics, high moisture and their cut surface, provide excellent conditions for microorganisms growth. As the feasibility of applying ionizing radiation to inactivate microorganisms is well known, this project will contribute to define the minimal and maximum doses in order to assure the hygienic quality and shelf life of this fresh pre-cut vegetables and fruits. Immunosuppressed patients have different classes of diets, depending on the immunosuppression grade. The hygienic quality was determined on the basis of levels 2 and 3, for (recovery and ambulatory patients respectively). The products investigated were carrots and tomatoes and the irradiation facility was a Cobalt Source. The microorganisms analysed were TBC, Mould and Yeasts, Total coliforms and faecal coliforms. Sensorial evaluation was carried out on the basis of a hedonic scale. (author)

  6. Reflex sympathetic dystrophy syndrome in renal transplanted patients under immunosuppression with tacrolimus.

    Science.gov (United States)

    Ybarra, J; Crespo, M; Torregrosa, J V; Fuster, D; Campistol, J M; Oppenheimer, F

    2003-12-01

    Reflex sympathetic dystrophy syndrome (RSDS), which probably has a multifactorial etiology, may appear after kidney transplantation. Its clinical manifestations include severe periarticular pain with inflammatory signs, especially in knees and ankles, causing functional disability. Symptoms develop during the first 3 months after transplantation and usually disappear 3 to 6 months later without sequelae. In renal transplant recipients it has previously been related to immunosuppressive treatment with cyclosporine. Therefore we had suggested that introducing tacrolimus could be a therapeutic option. We now present four cases of RSDS in kidney transplant recipients treated with tacrolimus. All but one patient were receiving tacrolimus monotherapy, excluding other drugs that might have been involved to cause the syndrome. It is also interesting that one of our cases develop RSDS long after transplantation when immunosuppressive treatment was changed. Symptoms correlated with an increase in alkaline phosphatase and with bone scintigraphy findings. All patients recovered without sequels 3 to 6 months afterward. In conclusion, RSDS is a relevant osteoarticular complication in patients receiving either anticalcineurinic drug (CyA or tacrolimus), even under monotherapy or with a low steroid dose.

  7. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis.

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St; Wadowsky, Robert M; Paterson, David L; McCurry, Kenneth R; Reinhart, Todd A; Husain, Shahid; Rinaldo, Charles R

    2007-02-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.

  8. Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis▿

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St.; Wadowsky, Robert M.; Paterson, David L.; McCurry, Kenneth R.; Reinhart, Todd A.; Husain, Shahid; Rinaldo, Charles R.

    2007-01-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses. PMID:17065270

  9. Radiostrontium-induced oncogenesis and the role of immunosuppression. Pt. 2

    International Nuclear Information System (INIS)

    Bierke, P.; Nilsson, A.

    1990-01-01

    The significance of depressed immune function for the development and progression of tumours induced by 90 Sr (mainly osteosarcomas and malignant lymphomas) was investigated in a series of experiments by comparing the tumour responses in normal mice with those in immunocompromised mice. The present paper (part II) reports on lympho-reticular (LR) and extraskeletal neoplastic lesions in male CBA/SU mice after exposure to different single doses of 90 Sr with or without additional immunosuppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. Neoplastic lesions in bone were reported in part I. The status of the animal's immune system and responsive ability were examined in parallel experiments. The tumor yields were analysed in relation to the dosage of 90 Sr and the immunosuppressive treatments employed. Although the incidences and latency times of induced tumours were clearly dose-dependent, they were never significantly influenced by ATx/ALG treatments. Thus, no substantial support was gained for the theory that the immune system plays a controlling or modifying role in 90 Sr carcinogenesis. The results, which are in agreement with the bone tumour responses, suggest that 90 Sr induced tumours either do not express the antigens necessary for immune rejection or that the decline in immune responsiveness induced by ATx/ALG was of little consequence for tumour development and spread. The pathogenesis of 90 Sr induced malignant lymphomas (MLs) and their immunophenotypes are discussed. (orig.)

  10. Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    Science.gov (United States)

    Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

    Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

  11. Amniotic membrane transplantation ineffective as additional therapy in patients with aggressive Mooren's ulcer.

    Science.gov (United States)

    Schallenberg, Maurice; Westekemper, Henrike; Steuhl, Klaus-Peter; Meller, Daniel

    2013-12-17

    Mooren's ulcer is a severe ulcerative inflammation of the cornea. The exact pathogenesis remains unclear. Therefore many therapies of Mooren's ulcer are recommended in literature. To shed more light on the ongoing question of optimal treatment of severe progressive Mooren's ulcer, we here report on a retrospective case series of patients treated with systemic immunosuppressive therapy and additional amniotic membrane transplantation. Medical records from seven patients (eleven eyes), 4 male and 3 female, with severe progressive Mooren's ulcer were analysed retrospectively. The mean follow up was 88.4 ± 80.8 months (range 12-232 month). A HLA-typing was performed in all patients. A systemic immunosuppressive therapy was administered in all patients. The amniotic membrane was transplanted after the base of the ulcer was resected. Multiple amniotic membrane transplantations were necessary in six patients. The visual outcome of all patients was poor. No patient achieved a visual acuity better than 20/630 Snellen chart. Five patients were positive for HLA-DQ2 and four patients were positive for HLA-DR17(3). The aggressive and highly inflammatory form of Mooren's ulcer is difficult to treat and the progression of the disease is hard to influence positively even under systemic immunosuppressive therapy. Therefore, the main intention of therapy is to achieve a stable epithelialized corneal surface without the risk of perforation. Amniotic membrane transplantation is not able to cure severe forms of Mooren's ulcer. However it supports the immunosuppressive therapy in acute situations as in critical corneal thinning.

  12. Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study

    OpenAIRE

    Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Ant?nio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

    2015-01-01

    Background Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Methods Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adher...

  13. A Marked Response to Immunosuppressive Intervention for Abruptly Occurring Cardiac Complications in a Case of Juvenile Systemic Sclerosis Overlapped with Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Tsunehisa Nagamori

    2017-01-01

    Full Text Available Juvenile-onset systemic sclerosis (jSSc is a rare condition, having unique characteristic features compared to adult-onset SSc. Although cardiac involvement (CI is known as a leading cause of mortality overall in SSc, the importance of CI in jSSc has not been emphasized. Here we present a 13-year-old female with jSSc overlapped with dermatomyositis (DM complicated CI. She developed skin thickness and induration, Raynaud’s phenomenon, digital pitting scars in fingertips, and skeletal myositis. Oral prednisolone and pulse methotrexate treatment led to the improvement of skin findings; however two weeks after the initiation she suddenly presented with muscle pain and dyspnea within a few days. Cardiac investigations then showed pericardiac effusion and diastolic dysfunction due to significant biventricular hypertrophy causing heart failure. As pericardiac effusion and exacerbation of skeletal myositis were evident, steroid pulse therapy was initiated. Unexpectedly, not only the myositis but also the CI including diastolic dysfunction was improved. She thereafter followed a favorable clinical course without reactivation of the CI or cardiac fibrosis. As a conclusion, close attention to CI must be paid in jSSc patients, especially when skeletal muscle involvement is evident and immunosuppressive therapy may be effective for CI in jSSc in cases where it occurs abruptly.

  14. Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection.

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    Teresa G Martins

    Full Text Available BACKGROUND: Buruli ulcer (BU is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX. Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of

  15. COMPARATIVE IMMUNO PATHOLOGICAL AND IMMUNOSUPPRESSIVE EEFECTS OF THREE DIFFERENT GUMBORO VACCINE STRAINS AGAINST NEWCASTLE DISEASE VACCINA TION IN BROILERS

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    R. M. Ayyub, A. Aslam, S. A. Khan and M. A. Munir1

    2003-12-01

    Full Text Available This project was carried out to study the comparative immunosuppressive effects of three different Gumboro live vaccine strains on Newcastle disease (NO vaccination. A total of 100 chicks were divided into four equal groups (A, B, C and O. Birds of all the groups were vaccinated against ND on 5th and 21st day of age. Specific Gumboro vaccine strain was given to specific group at 14th and 28th day of age. Group A, Band C were vaccinated with 228-E, D- 78 and Bursine-2, respectively, while group D was kept as control. Immune organs including bursa, thymus and spleen were examined for their gross and, histopathological changes, before and after Infectious Bursal disease (IBO vaccination. For this purpose, these organs were collected at 13th, 17th and 31st days of age. At 13th day (before 1BD vaccination no gross and histopathological lesions were observed in any bird of any group. At 17th and 31st day, severe lesions were noted in group A, moderate lesions in group B, mild lesions in group C and no lesions were observed in immune organs of group D. Haemagglutination inhibition (HI test showed that 228-E vaccine strain, (group A was highly immunosuppressive, D- 78 vaccine strain (group B was less immunosuppressive while Bursine-2 vaccine strain (group C was least immunosuppressive. No humoral immunosuppression was observed in unvaccinated control group D. This study suggests the use of Bursine-2 strain of IBD vaccine in a flock having risk of ND infection, as it has least immunosuppressive effect against ND vaccination.

  16. Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin.

    Science.gov (United States)

    Deters, M; Hütten, H; Kaever, V

    2013-01-15

    The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not-human cell lines. Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. To answer this question we investigated the interaction of both these substances on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation. OKT3-induced human PBMC proliferation was determined by measuring (3)H-thymidine incorporation. Influence of curcumin on interleukin-2 (IL-2) release and IκB-phosphorylation in PBMC was determined by ELISA and western blot, respectively. Curcumin-induced apoptosis and necrosis was analyzed by FACS analysis. Whereas curcumin completely inhibited OKT3-induced PBMC proliferation in a dose-dependent manner with an IC(50) of 2.8 μM, sirolimus could reduce PBMC proliferation dose-dependently only to a minimum of 28% at a concentration of 5 ng/ml (IC(50) 1.1 ng/ml). When curcumin was combined at concentrations of 1.25-2.5 μM with sirolimus at concentrations from 0.63 to 1.25 ng/ml the effects were synergistic. Combination of curcumin (1.25-2.5 μM) with sirolimus (5 ng/ml) showed additive effects. The effects after combination of curcumin at 5 μM with each sirolimus concentration and sirolimus at 10 ng/ml with each curcumin concentration were presumably antagonistic. We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3-activated PBMC. Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

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    Coutinho, Agnes E.; Chapman, Karen E.

    2011-01-01

    Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here. PMID:20398732

  18. Immunosuppressant Medication-Induced Lower Extremity Pain After Combined Liver and Kidney Transplant: A Case Report.

    Science.gov (United States)

    Mohideen, Thanzeela Kausar; Wu, Hong

    2018-03-01

    Calcineurin inhibitors are imperative in the success of a transplanted organ. However, these immunosuppressants can lead to a rare complication known as calcineurin inhibitor-induced pain syndrome, which may not be recognized early and managed appropriately. We present a case of a 35-year-old woman who underwent a combined liver/kidney transplant and developed lower extremity pain while being maintained on tacrolimus. This case illustrates a patient with previously reported characteristic clinical features of calcineurin inhibitor-induced pain syndrome in addition to uncharacteristic neuropathic symptoms and imaging findings. The patient was treated successfully with gabapentin, calcitonin nasal spray, and acupuncture. Early recognition of this syndrome can help improve a patient's quality of life. V. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  19. [Kaposi sarcoma and HHV-8: a model of cutaneous cancer in immunosuppressed patients].

    Science.gov (United States)

    Dupin, Nicolas; Deleuze, Jean

    2014-03-01

    The virus HHV-8 will celebrate its twentieth birthday by the end of this year and its relationships with Kaposi sarcoma are not completely elucidated. HHV-8 is an enigmatic virus, with an inhomogeneous distribution, a salivary transmission while it is not an ubiquitous virus, at least in western countries. However, HHV-8 has a unique genetic equipment rending is role in Kaposi sarcoma more than plausible. While the virus is necessary, it appears that it is not sufficient as the development of Kaposi sarcoma is frequently associated with immunosuppression whatever the cause (iatrogenic, viral, age-related). Kaposi sarcoma should be more considered as an opportunistic tumour than a viral-induced cancer and the best treatment for Kaposi sarcoma is immune restoration at least when it is possible.

  20. Simple aromatics identified with a NFAT-lacZ transcription assay for the detection of immunosuppressants.

    Science.gov (United States)

    Burres, N S; Premachandran, U; Hoselton, S; Cwik, D; Hochlowski, J E; Ye, Q; Sunga, G N; Karwowski, J P; Jackson, M; Whittern, D N

    1995-05-01

    Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.

  1. Can immunosuppressive therapy facilitate the diagnosis and affect the clinical signs of canine scabies? A retrospective study of 79 cases.

    Science.gov (United States)

    Souza, Clarissa P; Torres, Sheila M F; Koch, Sandra N; Rendahl, Aaron; Verocai, Guilherme G

    2016-06-01

    Scabies infestation is one of the most pruritic dermatoses of dogs. It is often misdiagnosed and dogs are treated with immunomodulatory drugs (IMD) to relieve pruritus. The primary goals of this study were to determine the impact of IMD on skin scraping results, pruritus level and extent of skin lesions, and to evaluate whether disease duration is associated with positive skin scrapings and contagion. Seventy nine dogs with a final diagnosis of scabies. Inclusion in this retrospective study required a positive skin scraping for scabies or a clinical response to an acaricidal treatment trial. The average pruritus score of dogs that received IMD (8.71) was significantly higher than those that did not (7.43; P = 0.03). However, there were no significant differences in either the rates of positive skin scrapings (79.6% versus 59.1%; P = 0.13) or the mean number of body sites affected (3.8 versus 3.4; P = 0.30) between dogs that received IMD and those that did not. Neither skin scraping status nor duration of clinical signs were correlated with a report of contagion within the household. IMD was associated with a significant increase in the pruritus level, but not with the mean number of lesional body sites. Dogs exposed to IMD had a 20.5% higher rate of positive skin scrapings. This difference could be clinically relevant and lack of statistical significance may indicate an underpowered study. © 2016 ESVD and ACVD.

  2. GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) trial: study protocol for a phase II/III randomised controlled trial.

    Science.gov (United States)

    Oughton, Jamie B; Collett, Laura; Howard, Dena R; Hockaday, Anna; Munir, Talha; McMahon, Kathryn; McParland, Lucy; Dimbleby, Claire; Phillips, David; Rawstron, Andy C; Hillmen, Peter

    2017-07-26

    Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an independent predictor of survival even with a variety of different treatment approaches and regardless of the line of therapy. GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is a seamless phase II/III, multi-centre, randomised, controlled, open, parallel-group trial for patients with CLL who have recently responded to chemotherapy. Participants will be randomised to receive either obinutuzumab (GA-101) consolidation or no treatment (as is standard). The phase II trial will assess safety and short-term efficacy in order to advise on continuation to a phase III trial. The primary objective for phase III is to assess the effect of consolidation therapy on progression-free survival (PFS). One hundred eighty-eight participants are planned to be recruited from forty research centres in the United Kingdom. There is evidence that achieving MRD eradication with alemtuzumab consolidation is associated with improvements in survival and time to progression. This trial will assess whether obinutuzumab is safe in a consolidation setting and effective at eradicating MRD and improving PFS. ISRCTN, 64035629 . Registered on 12 January 2015. EudraCT, 2014-000880-42 . Registered on 12 November 2014.

  3. Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer?

    Science.gov (United States)

    COGHILL, Anna E.; SHIELS, Meredith S.; RYCROFT, Randi K.; COPELAND, Glenn; FINCH, Jack L.; HAKENEWERTH, Anne M.; PAWLISH, Karen S.; ENGELS, Eric A.

    2015-01-01

    Objective Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. Design Population-based registry Methods We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991–2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons to the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. Results HIV-infected persons had an excess risk of rectal SCC compared to the general population (SIR=28.9; 95%CI 23.2–35.6), similar to the increase for anal SCC (SIR=37.3). Excess rectal SCC risk was most pronounced among HIV-infected men who have sex with men (MSM, SIR=61.2). Risk was not elevated for rectal non-SCC (SIR=0.88) or colon non-SCC (SIR=0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio=1.86; 95%CI 1.04–3.31). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. Conclusions HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumor location is needed to prove that rectal SCC is a distinct entity. PMID:26372482

  4. Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

    International Nuclear Information System (INIS)

    Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

    1988-01-01

    From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) [or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)], 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group

  5. Involvement of Regulatory T Cells in the Immunosuppression Characteristic of Patients with Paracoccidioidomycosis▿

    Science.gov (United States)

    Ferreira, Maria Carolina; de Oliveira, Rômulo Tadeu Dias; da Silva, Rosiane Maria; Blotta, Maria Heloisa Souza Lima; Mamoni, Ronei Luciano

    2010-01-01

    Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor β (TGF-β). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-β neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role. PMID:20643858

  6. Antigenic and immunosuppressive properties of a trimeric recombinant transmembrane envelope protein gp41 of HIV-1.

    Directory of Open Access Journals (Sweden)

    Michael Mühle

    Full Text Available The transmembrane envelope (TM protein gp41 of the human immunodeficiency virus-1 (HIV-1 plays an important role during virus infection inducing the fusion of the viral and cellular membranes. In addition, there are indications that the TM protein plays a role in the immunopathogenesis leading to the acquired immunodeficiency syndrome (AIDS. Inactivated virus particles and recombinant gp41 have been reported to inhibit lymphocyte proliferation, as well as to alter cytokine release and gene expression. The same was shown for a peptide corresponding to a highly conserved domain of all retroviral TM proteins, the immunosuppressive domain. Due to its propensity to aggregate and to be expressed at low levels, studies comprising authentic gp41 produced in eukaryotic cells are extremely rare. Here we describe the production of a secreted, soluble recombinant gp41 in 293 cells. The antigen was purified to homogeneity and characterised thoroughly by various biochemical and immunological methods. It was shown that the protein was glycosylated and assembled into trimers. Binding studies by ELISA and surface plasmon resonance using conformation-specific monoclonal antibodies implied a six-helix bundle conformation. The low binding of broadly neutralising antibodies (bnAb directed against the membrane proximal external region (MPER suggested that this gp41 is probably not suited as vaccine to induce such bnAb. Purified gp41 bound to monocytes and to a lesser extent to lymphocytes and triggered the production of specific cytokines when added to normal peripheral blood mononuclear cells. In addition, gp41 expressed on target cells inhibited the antigen-specific response of murine CD8+ T cells by drastically impairing their IFNγ production. To our knowledge, this is the first comprehensive analysis of a gp41 produced in eukaryotic cells including its immunosuppressive properties. Our data provide another line of evidence that gp41 might be directly involved in

  7. Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    Science.gov (United States)

    Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

    2016-01-01

    Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

  8. Resistance of a lizard (the green anole, Anolis carolinensis; Polychridae) to ultraviolet radiation-induced immunosuppression

    Science.gov (United States)

    Cope, R.B.; Fabacher, D.L.; Lieske, C.; Miller, C.A.

    2001-01-01

    The green anole (Anolis carolinensis) is the most northerly distributed of its Neotropical genus. This lizard avoids a winter hibernation phase by the use of sun basking behaviors. Inevitably, this species is exposed to high doses of ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B (UV-B) radiation secondary to stratospheric ozone depletion and habitat perturbation potentially place this species at risk of UVR-induced immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85 kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative doses of 192 kJ/m2 UV-B, 2.04 × 103 kJ/m2 UV-A) did not suppress the anole's acute or delayed type hypersensitivity (DTH) response to horseshoe crab hemocyanin. In comparison with the available literature UV-B doses as low as 0.1 and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans, respectively. Exposure of anoles to UVR did not result in the inhibition of ex vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2 have been reported to suppress murine splenic/peritoneal macrophage phagocytosis and nitric oxide production. These preliminary studies demonstrate the resistance of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin contained two peaks in the ultraviolet wavelength range that could be indicative of photoprotective substances. However, the resistance of green anoles to UVR is probably not completely attributable to absorption by UVR photoprotective substances in the skin but more likely results from a combination of other factors including absorption by the cutis and absorption and reflectance by various components of the dermis.

  9. Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats.

    Science.gov (United States)

    McLuckie, Alicia J; Barrs, Vanessa R; Wilson, Bethany; Westman, Mark E; Beatty, Julia A

    2017-03-14

    Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV) infection, making the interactions between feline immunodeficiency virus (FIV) and Felis catus gammaherpesvirus 1 (FcaGHV1) pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18) or feline leukemia virus (FeLV)-infected (P2, n = 57) patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57). In contrast, FIV/FeLV-co-infected cats (P3, n = 5) were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068), and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3) had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4). In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

  10. A Pilot Randomized Controlled Trial to Promote Immunosuppressant Adherence in Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Cukor, Daniel; Ver Halen, Nisha; Pencille, Melissa; Tedla, Fasika; Salifu, Moro

    2017-01-01

    Nonadherence to immunosuppressant medication is a prevalent practice among kidney transplant recipients and has been associated with increased risk for graft failure and economic burden. The aim of this pilot study was to test whether a culturally sensitive cognitive-behavioral adherence promotion program could significantly improve medication adherence to tacrolimus prescription as measured by telephone pill counts among kidney transplant recipients. Thirty-three adult transplant recipients were less than 98% adherent to tacrolimus prescription based on 3 telephone pill counts and were randomized either to the 2-session cognitive-behavioral adherence promotion program or to standard care. The curriculum was developed from an iterative process with transplant recipients into a 2-session group program that provided psychoeducation, addressed barriers to adherence, fostered motivation to improve adherence behavior, and discussed cultural messages on adherence behavior. The intervention group displayed significantly higher levels of adherence when compared to the control group (t = 2.2, p = 0.04) and. similarly, when the amount of change was compared between the groups, the intervention group showed more change than the control condition (F (22,1) = 12.005, p = 0.003). Tacrolimus trough concentration levels were used as a secondary measure of adherence and, while there were no significant between-group differences for mean trough concentration levels, the variability in the trough levels did significantly decrease over time indicating more consistent pill-taking behavior in the intervention group. There is preliminary support for the pilot program as a successful intervention in helping patients with their immunosuppressant medication. © 2016 S. Karger AG, Basel.

  11. Immunosuppression with FK506 has no influence on fracture healing in the rat.

    Science.gov (United States)

    Voggenreiter, Gregor; Siozos, Patrizia; Hunkemöller, Eva; Heute, Stefan; Schwarz, Markus; Obertacke, Udo

    2005-08-01

    Immunosuppressant drugs like cyclosporine A and FK506 are widely used for solid organ transplantation. They are accelerating bone remodeling but cause net bone loss. The aim of this study was to investigate the effect of FK506 on fracture healing in the rat. Eighty Lewis rats were divided into four groups, which received FK506 (1 mg/kg BW) or no treatment for 2 or 4 weeks, beginning after production of a closed, nondisplaced unilateral tibial fracture. Radiographic, histological, and biomechanical studies were used to evaluate fracture healing and histomorphometric analysis of the tibial metaphysis of the intact contralateral side was performed. Radiographs revealed no difference of the healing of the control fractures compared with the fractures in the FK506-treated group at 2 and 4 weeks. The mechanical parameters of the tested contralateral intact tibiae and of the fracture callus demonstrated no difference between control and immunosuppressed animals. Tibial bone histomorphometry revealed increased measures of bone formation and bone resorption, accompanied by a significant reduction of percent trabecular area. At 4 weeks, the fractures showed osseous healing with woven bone at the fracture site and only minimal amounts of cartilage. Histological grading was not different between the control and the FK506 group at both time points. We conclude that systemic application of FK506 has no biomechanical and histological effects of experimental fracture healing in the rat. However, resorption far in excess of formation leads to a net bone loss in the trabecular bone of the tibia that has no effect on the stability of the intact bone.

  12. Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

    Directory of Open Access Journals (Sweden)

    Alicia J. McLuckie

    2017-03-01

    Full Text Available Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV infection, making the interactions between feline immunodeficiency virus (FIV and Felis catus gammaherpesvirus 1 (FcaGHV1 pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18 or feline leukemia virus (FeLV-infected (P2, n = 57 patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57. In contrast, FIV/FeLV-co-infected cats (P3, n = 5 were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068, and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3 had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4. In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

  13. Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression.

    Science.gov (United States)

    Lachmann, Gunnar; von Haefen, Clarissa; Kurth, Johannes; Yuerek, Fatima; Spies, Claudia

    2018-01-01

    Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively ( od ) until day 5 after surgery ( pod5 ). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5. Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.

  14. Soluble Immune Response Suppressor (SIRS): Reassessing the immunosuppressant potential of an elusive peptide.

    Science.gov (United States)

    Webb, David R

    2016-10-01

    A previously studied immunosuppressive cytokine, Soluble Immune Response Suppressor (SIRS), may have relevance to current studies of immune suppression in a variety of human disease states. Despite extensive efforts using experimental models, mainly in mice, much remains to be discovered as to how autoimmune cells in mice and humans escape normal regulation and, conversely, how tumor cells evade evoking an immune response. It is the contention of this commentary that the literature pre-2000 contain results that might inform current studies. The broadly immunosuppressive protein, SIRS, was studied extensively from the 1970s to 1990s and culminated in the determination of the n-terminal 21mer sequence of this 15kDa protein which had high homology to the short neurotoxins from sea snakes, that are canonical members of the three finger neurotoxin superfamily (3FTx). It was not until 2007 that the prophylactic administration of the synthetic N-terminal peptide of the SIRS 21mer, identical to the published sequence, was reported to inhibit or delay the development of two autoimmune diseases in mice: experimental allergic encephalomyelitis (EAE) and type I diabetes (T1D). These findings were consistent with other studies of the 3FTx superfamily as important probes in the study of mammalian pharmacology. It is the perspective of this commentary that SIRS, SIRS peptide and the anti-peptide mAb, represent useful, pharmacologically-active probes for the study of the immune response as well as in the potential treatment of autoimmune, inflammatory diseases and cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Protective effect of intravitreal administration of tresperimus, an immunosuppressive drug, on experimental autoimmune uveoretinitis.

    Science.gov (United States)

    Bousquet, Elodie; Camelo, Serge; Leroux les Jardins, Guillaume; Goldenberg, Brigitte; Naud, Marie-Christine; Besson-Lescure, Bernadette; Lebreton, Luc; Annat, Jocelyne; Behar-Cohen, Francine; de Kozak, Yvonne

    2011-07-20

    To test the efficiency of locally administrated tresperimus in experimental autoimmune uveoretinitis (EAU). EAU was induced in Lewis rats by S-antigen (S-Ag) immunization. Three intravitreal injections of tresperimus (prevention or prevention/treatment protocols) were performed at different time points after immunization. The pharmacokinetics of tresperimus was evaluated in the ocular tissues and plasma. The in vitro effect of tresperimus was evaluated on macrophages. EAU was graded clinically and histologically. Blood ocular barrier permeability was evaluated by protein concentration in ocular fluids. Immune response to S-Ag was examined by delayed type hypersensitivity, the expression of inflammatory cytokines in lymph nodes, ocular fluids and serum by multiplex ELISA, and in ocular cells by RT-PCR. In vitro, tresperimus significantly reduced the production of inflammatory cytokines by lipopolysaccharide-stimulated macrophages. In vivo, in the treatment protocol, efficient tresperimus levels were measured in the eye but not in the plasma up to 8 days after the last injection. Tresperimus efficiently reduced inflammation, retinal damage, and blood ocular barrier permeability breakdown. It inhibited nitric oxide synthase-2 and nuclear factor κBp65 expression in ocular macrophages. IL-2 and IL-17 were decreased in ocular media, while IL-18 was increased. By contrast, IL-2 and IL-17 levels were not modified in inguinal lymph nodes draining the immunization site. Moreover, cytokine levels in serum and delayed type hypersensitivity to S-Ag were not different in control and treated rats. In the prevention/treatment protocol, ocular immunosuppressive effects were also observed. Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation.

  16. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients.

    Science.gov (United States)

    Fairfield, Cameron; Penninga, Luit; Powell, James; Harrison, Ewen M; Wigmore, Stephen J

    2018-04-09

    Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017. Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed-effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a

  17. Immunomodulatory therapies for acute pancreatitis

    Science.gov (United States)

    Li, Jing; Yang, Wen-Juan; Huang, Lu-Ming; Tang, Cheng-Wei

    2014-01-01

    It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. PMID:25493006

  18. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    NARCIS (Netherlands)

    Hampras, S.S.; Sucheston-Campbell, L.E.; Cannioto, R.; Chang-Claude, J.; Modugno, F.; Dork, T.; Hillemanns, P.; Preus, L.; Knutson, K.L.; Wallace, P.K.; Hong, C.C.; Friel, G.; Davis, W.; Nesline, M.; Pearce, C.L.; Kelemen, L.E.; Goodman, M.T.; Bandera, E.V.; Terry, K.L.; Schoof, N.; Eng, K.H.; Clay, A.; Singh, P.K.; Joseph, J.M.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Baker, H.; Bean, Y.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Cook, L.S.; Cramer, D.W; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Despierre, E.; Dicks, E.; Doherty, J.A.; Bois, A. du; Durst, M.; Easton, D.; Eccles, D.; Edwards, R.P.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Gronwald, J.; Harrington, P.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hogdall, C.; Hogdall, E.; Hosono, S.; Iversen, E.S.; Jakubowska, A.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.L.M.; Klapdor, R.; Kolomeyevskaya, N.; Krakstad, C.; Kjaer, S.K.; Kruszka, B.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Liu, S.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.A.G.; Matsuo, K.; McGuire, V.; et al.,

    2016-01-01

    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and

  19. A case report of vascular catheter-associated bacteremia caused by Mycobacterium tuberculosis in a non-immunosuppressed patient

    Directory of Open Access Journals (Sweden)

    PETRILLO Victor Flávio

    1999-01-01

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