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Sample records for chronic immune thrombocytopenic

  1. Chronic immune thrombocytopenic purpura. New agents.

    Science.gov (United States)

    Rodeghiero, F; Ruggeri, M

    2009-01-01

    First generation thrombopoietic growth factors (rhTPO and PEG-rHuMGDF), investigated in the early 2000s, proved effective in increasing platelet count in normal volunteers, in thrombocytopenia due to chemotherapy and also in a few cases of immune thrombocytopenic purpura (ITP). These agents did not complete their clinical development since one of them induced antibodies in the recipients that cross reacted with endogenous thrombopoietin (TPO), thus causing thrombocytopenia. This promoted the ingenious design of a new generation of thrombopoietic growth factors having no sequence homology with natural TPO. The two main agents are romiplostim, a peptibody already approved for clinical use in USA and eltrombopag, a non-peptide, orally active small molecule. In open label and placebo-controlled trials both agents proved to predictably increase platelet count in normal volunteers and in patients with ITP. With appropriate dosages (1-10 microg/kg weekly sub cutaneously for romiplostim; 50-75 mg/die per os for eltrombopag ) a platelet increase becomes significant after 7-10 days and peaks between 10-14 days. By discontinuing treatment, platelet count returns to baseline level in 10-15 days. The response rate with both agents is above 70-80%, also in patients that had undergone several lines of treatment, or that have failed splenectomy. The response is maintained during the treatment, but is almost invariably lost even after several months of successful administration. Due to the lack of a curative potential and to the incomplete knowledge of long-term side effects, the place of these new drugs in the management of ITP is still unsettled and their use is best restricted to refractory patients or in preparation of splenectomy. It seems however that a new paradigm in the treatment of ITP has been established where the focus is not on reducing platelet consumption but on increasing platelet production.

  2. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura : a double-blind randomised controlled trial

    NARCIS (Netherlands)

    Kuter, David J.; Bussel, James B.; Lyons, Roger M.; Pullarkat, Vinod; Gernsheimer, Terry B.; Senecal, Francis M.; Aledort, Louis M.; George, James N.; Kessler, Craig M.; Sanz, Miguel A.; Liebman, Howard A.; Slovick, Frank T.; de Wolf, J. Th M.; Bourgeois, Emmanuelle; Guthrie, Troy H.; Newland, Adrian; Wasser, Jeffrey S.; Hamburg, Solomon I.; Grande, Carlos; Lefrere, Francois; Lichtin, Alan Eli; Tarantino, Michael D.; Terebelo, Howard R.; Viallard, Jean-Francois; Cuevas, Francis J.; Go, Ronald S.; Henry, David H.; Redner, Robert L.; Rice, Lawrence; Schipperus, Martin R.; Guo, D. Matthew; Nichol, Janet L.

    2008-01-01

    Background Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic

  3. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

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    Sheema, Khan; Arshi, Naz; Farah, Naz; Imran, Sheikh

    2017-01-01

    Background. Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET) on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count 3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA). Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 109/l to 94.2 ± 26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia.

  4. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

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    Khan Sheema

    2017-01-01

    Full Text Available Background. Idiopathic thrombocytopenic purpura (ITP is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count 3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA. Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6% were male and 53 (62.3% were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA was detected in 34 (40% patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56±21.7 × 109/l to 94.2±26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia.

  5. Quantifying the reduction in immunoglobulin use over time in patients with chronic immune thrombocytopenic purpura receiving romiplostim (AMG 531)

    NARCIS (Netherlands)

    Pullarkat, Vinod A.; Gernsheirner, Terry B.; Wasser, Jeffrey S.; Newland, Adrian; Guthrie, Troy H.; de Wolf, Joost Th. M.; Stewart, Ron; Berger, Dietmar

    2009-01-01

    Patients with Immune thrombocytopenic purpura (ITP) often require immunoglobulin (Ig) therapy with intravenous 19 (IVIG) or anti-D to prevent or treat the serious bleeding events. Because the thrombopoietin (TPO) mimetic romiplostim (AMG 531; Nplate) elevates platelet counts in patients with chronic

  6. Is Tc-99m Sulfur Colloid Scintigraphy Necessary in Chronic Immune Thrombocytopenic Purpura Before Splenectomy?

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    Ilçe HT et al.

    2011-05-01

    Full Text Available One of the most common reasons for elective splenectomy on adults ischronic immune thrombocytopenic purpura. It is characterized by thrombocyte destruction in spleen, so, management of splenectomy is the gold standard. However if there is remnant spleen tissue postoperatively it cause to going on thrombocytopenia. The principal reason of remnant spleen tissue is accessory spleen. So it is important to detect this tissue pre or postoperatively. Thirty years old, male patient underwent splenectomy four years ago because of chronic immunethrombocytopenic purpura. When thrombocytopenia recurrence occurredabdominal ultrasonography was performed and there was no abnormal sign. Then, Tc–99 m Sulfur Colloid Spleen Scintigraphy was performed and spleen tissue was detected in left hypochondriac region. Tc-99mSulfur Colloid Spleen Scintigraphy is one of the imaging method for accessory spleen. Especially if it is performed preoperatively the surgeon can be careful during the operation and at the same time detected accessory spleen was removed and recurrence can be prevented.

  7. Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

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    Boyers, Dwayne; Jia, Xueli; Jenkinson, David; Mowatt, Graham

    2012-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^⁹/L and 400 × 10^⁹/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed

  8. Tuberculosis presenting as immune thrombocytopenic purpura

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    Bahadir-Erdogan Beril

    2004-09-01

    Full Text Available Abstract Background Although various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event. Case Presentation We report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy. Conclusion Immune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.

  9. Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle

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    Andreas Rank

    2010-05-01

    Full Text Available Andreas Rank, Oliver Weigert, Helmut OstermannMedizinische Klinik III – Grosshadern, Klinikum der Ludwig Maximilians-Universitaet Munich, Munich, GermanyAbstract: Traditionally, anti-platelet autoantibodies accelerating platelet clearance from the peripheral circulation have been recognized as the primary pathopysiological mechanism in chronic immune thrombocytopenia (ITP. Recently, increasing evidence supports the co-existence of insufficient megakaryopoiesis. Inadequate low thrombopoietin (TPO levels are associated with insufficient proliferation and differentiation of megakaryocytes, decreased proplatelet formation, and subsequent platelet release. Recently two novel activators of TPO receptors have been made available: romiplostim and eltrombopag. In several phase III studies, both agents demonstrated increase of platelet counts in about 80% of chronic ITP patients within 2 to 3 weeks. These agents substantially broaden the therapeutic options for patients with chronic ITP although long-term results are still pending. This review will provide an update on the current conception of underlying mechanisms in ITP and novel, pathophysiologically based treatment options.Keywords: immune thrombocytopenia, romiplostim, eltrombopag, megakaryopoiesis

  10. Thrombopoietin mimetic agents in the management of immune thrombocytopenic purpura.

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    Newland, Adrian

    2007-10-01

    Thrombopoietin (TPO) is a potent endogenous cytokine and the principal regulator of platelet production. Advances in the understanding of the structure of TPO enabled development of the first generation of thrombopoietic growth factors, recombinant human thrombopoietin (rhTPO) and pegylated human recombinant megakaryocyte growth and development factor (PEG-rHuMGDF). Clinical results showed that these agents were effective in promoting increases in platelet counts in a variety of thrombocytopenic disorders. However, clinical development was halted when studies demonstrated risk for autoantibody formation with cross-reactivity to endogenous TPO. A second generation of thrombopoietic growth factors, including TPO peptide and nonpeptide mimetics and TPO agonist antibodies, utilizing different mechanisms from recombinant growth factors to promote platelet production, are currently in development. The TPO peptide mimetic AMG 531 and the nonpeptide mimetic eltrombopag are in advanced clinical trials and have both resulted in dose-dependent increases in platelets in healthy subjects and in significant increases in platelets in patients with chronic immune thrombocytopenic purpura (ITP). Clinical trials are also being conducted to examine the efficacy and safety of eltrombopag to treat thrombocytopenia in hepatitis C virus (HCV)-infected individuals. These agents appear to be well tolerated and the formation of autoantibodies appears to be limited to first-generation growth factors. Increases in marrow reticulin have been demonstrated with some growth factors, but this appears to be a reversible phenomenon and is not associated with formation of collagen fibrosis. There appears to be no increased incidence of thrombotic events in patients who achieve high platelet counts with growth factor treatments, and although occasional thrombotic events have been reported, their association to the treatment is uncertain. While there is evidence that activation of signaling pathways

  11. Recurrent Acute Myocardial Infarction in Patients with Immune Thrombocytopenic Purpura

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    Fengyi Shen

    2014-01-01

    Full Text Available Immune thrombocytopenic purpura (ITP, also known as idiopathic thrombocytopenic purpura, is an acquired immune-mediated disease of adults and children characterized by a transient or persistent decrease of platelets and, depending upon the degree of thrombocytopenia, an increased risk of bleeding. The use of standard treatments for acute myocardial infarction (AMI, such as antiplatelet agents and anticoagulants, pose serious problems in patients with ITP due to the potential higher risk of bleeding complications. There are no current guidelines available for management of ITP patients with AMI. In this brief review of the limited available literature, we discuss the proposed pathophysiological link between ITP and arterial thrombosis and the challenging medical and interventional treatment of these patients.

  12. Splenectomy during pregnancy: treatment of refractory immune thrombocytopenic purpura

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    Mahey, Reeta; Kaur, Simran Deep; Chumber, Sunil; Kriplani, Alka; Bhatla, Neerja

    2013-01-01

    Immune thrombocytopenic purpura (ITP) complicates 1–2/10 000 pregnancies and accounts for 5% of cases of pregnancy-associated thrombocytopenia. Corticosteroids and intravenous immunoglobulin remain the first-line therapy in pregnancy, and a majority of pregnant women respond to this conventional therapy. Other cytotoxic and immunosuppressive agents used for treatment in non-pregnant patients, for example, danazol, cyclophosphamide, vinca alkaloids and azathioprine, are potential teratogens an...

  13. Impact of chronic Immune Thrombocytopenic Purpura (ITP on health-related quality of life: a conceptual model starting with the patient perspective

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    George James N

    2008-02-01

    Full Text Available Abstract Background Immune thrombocytopenic purpura (ITP, a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL. Methods A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. Results The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. Conclusion ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP.

  14. Treatment of immune thrombocytopenic purpura: focus on eltrombopag

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    Lawrence Rice

    2009-03-01

    Full Text Available Lawrence RiceWeill Cornell Medical College, The Methodist Hospital, Houston, Texas, USAAbstract: Immune thrombocytopenic purpura (ITP is a relatively common autoimmune disorder in which antibodies are produced to circulating platelets. Symptoms can be mild, but for most patients the risk of severe bleeding is unacceptable and treatment is required. Glucocorticoids followed by splenectomy had been the mainstays of therapy. High dose intravenous immunoglobulin and anti-RhD therapy are available for patients with severe illness, but produce only temporary benefit. Rituximab may provide more durable responses, danazol may be underutilized, and immunosuppressants and cytotoxic agents are less often required. Recently the pathophysiology of ITP has been more clearly elucidated, particularly the importance of decreased production of platelets in most patients and the very blunted rise that occurs in serum thrombopoietin (TPO. The isolation of TPO and better understanding of its role in thrombopoiesis has led to the development of new highly effective treatments. TPO analogs had some successes in treating highly refractory ITP patients but were taken out of development due to TPO-antibody induction. Two second-generation TPO-mimetics, romiplostim and the orally available eltrombopag, have recently been licensed in some territories for the treatment of ITP. Approval of eltrombopag was based on results from Phase II and III placebo-controlled clinical trials and a long-term extension study. About 80% of patients achieve significant increases in platelet count (11% of placebo patients, with reduced bleeding and reduced use of concomitant medications; responses are often durable with no tachyphylaxis. The side effects of eltrombopag are generally mild and not worse than placebo, although there are concerns about hepatic dysfunction, and the potentials for thromboses, marrow reticulin fibrosis, rebound thrombocytopenia and cataracts. This is an important new

  15. A review of immune thrombocytopenic purpura: focus on the novel thrombopoietin agonists

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    Meaghan Khan

    2010-03-01

    Full Text Available Meaghan Khan, Joseph MikhaelDivision of Hematology – Oncology, Scottsdale, AZ, USAAbstract: Immune thrombocytopenic purpura (ITP is an autoimmune disorder that is characterized by antibody-mediated platelet destruction and decreased platelet production. ITP and its treatments have been recognized to cause diminished quality of life in those afflicted with this illness on levels comparable to other chronic diseases. The disease can be self-limiting, but in adults it often is a chronic process requiring medical intervention to maintain appropriate platelet counts and to reduce bleeding events. Many patients go on to develop disease that is refractory to current interventions. Historically, the aim of treatment has been focused on reducing the amount of antibody-mediated destruction but newer therapies have centered on the decreased platelet production. Two new medications that target production of platelets have recently been USA, Food and Drug Administration (FDA approved for the treatment of chronic relapsing ITP. Here, we provide an overview of ITP and a comprehensive review of the newest therapies aimed at the stimulation of platelet production.Keywords: immune thrombocytopenic purpura, therapy, thrombopoietin, romiplostim, AMG 531, eltrombopag

  16. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

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    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  17. Immune thrombocytopenic purpura as sole manifestation in a case of acute hepatitis A.

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    Tanir, Gönül; Aydemir, Cumhur; Tuygun, Nilden; Kaya, Ozge; Yarali, Neşe

    2005-12-01

    Acute hepatitis due to hepatitis A virus is usually a benign selflimiting disease during childhood. Although many viral infections such as hepatitis B virus, Parvovirus, and Epstein-Barr virus are associated with extrahepatic autoimmune phenomena, such manifestations are rare in patients with acute hepatitis A infection. Immune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. Immune thrombocytopenic purpura is rarely reported as a manifestation of acute hepatitis A. We report a five-year-old boy with immune thrombocytopenic purpura as the sole manifestation of anicteric acute hepatitis A infection. Acute hepatitis A should be included in the differential diagnosis of immune thrombocytopenic purpura.

  18. Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura.

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    Schmidt, E E; MacDonald, I C; Groom, A C

    1991-09-15

    The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction.

  19. Acute immune thrombocytopenic purpura triggered by insect bite

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    Namdev R

    2009-03-01

    Full Text Available Idiopathic Thrombocytopenic Purpura (ITP is a blood disorder characterized by an abnormal decrease in the number of platelets in the blood. Acute thrombocytopenic purpura is most commonly seen in young children, with a sudden onset, following a viral illness, vaccination or an insect bite. The report is a rare case of ITP, which was triggered by a honey-bee bite and caused continuous intermittent bleeding from the gingival sulcular region of the maxillary left permanent first molar, and ecchymotic spots on the forehead, scalp, and lower limbs. A complete hemogram revealed severe thrombocytopenia with platelet count as low as 15,000/mm3. The patient was immediately hospitalized and administered platelet replacement and medication. With this report, the authors, as dentists, emphasize the significance of recognition, early diagnosis, and referral of such patients with bleeding disorders to specialized centers, for prompt treatment.

  20. Long-term outcomes of combined chemotherapy in chronic refractory idiopathic thrombocytopenic purpura

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    TAO Jie; HUANG Ying; LI Hong-qiang; WANG Ting-ting; WANG Xiao-yan; JI Lin-xiang; YANG Ren-chi

    2007-01-01

    @@ Adult idiopathic thrombocytopenic purpura (ITP) is a chronic acquired organ-specific autoimmune hemorrhagic disease characterized by the production of auto-antibodies against antigens on the membranes of platelet, resulting in enhanced Fc-mediated destruction of the platelets by macrophages in the reticuloendothelial system.

  1. Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura.

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    Suntsova, Elena V; Demina, Irina M; Ignatova, Anastasia A; Ershov, Nikolay M; Trubina, Natalia M; Dobrynina, Juliya; Serkova, Irina V; Supik, Zhanna S; Orekhova, Ekaterina V; Hachatryan, Lili A; Kotskaya, Natalia N; Pshonkin, Aleksey V; Maschan, Aleksey A; Novichkova, Galina A; Panteleev, Mikhail A

    2017-03-07

    It has been suggested that platelet function in chronic immune thrombocytopenic purpura (ITP) may be abnormal. Thrombopoietin mimetics used for treatment can affect it, but the data remain limited. We investigated platelet function of 20 children diagnosed with severe ITP (aged 1-16 years, 12 females and eight males). Platelet functional activity in whole blood was characterized by flow cytometry before and after stimulation with SFLLRN plus collagen-related peptide. Levels of CD42b, PAC1, and CD62P, but not CD61 or annexin V, were significantly increased (P < 0.05) in resting platelets of patients before treatment compared with healthy donors. On average, PAC1 and CD62P in patients after activation were also significantly elevated, although some patients failed to activate integrins. Romiplostim (1-15 μg/kg/week s.c.) was prescribed to seven patients, with clinical improvement in six. Interestingly, one patient had clinical improvement without platelet count increase. Eltrombopag (25-75 mg/day p.o.) was given to four patients, with positive response in one. Others switched to romiplostim, with one stable positive response, one unstable positive response, and one non-responding. Platelet quality improved with romiplostim treatment, and their parameters approached the normal values. Our results suggest that platelets in children with severe ITP are pre-activated and abnormal, but improve with treatment.

  2. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study

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    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-01-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequen...

  3. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus

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    Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m2 (P75). A biochemical analysis showed 1×109 platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient’s glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin. PMID:27026836

  4. Variant clinical courses in children with immune thrombocytopenic purpura: Sixteen year experience of a single medical center

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    Işın Yaprak

    2010-09-01

    Full Text Available Objective: Immune thrombocytopenic purpura (ITP is the most common cause of acquired thrombocytopenia in children. The objective of this study was to evaluate the presenting features, variation in the clinical courses, initial response rate to therapy, and long-term outcome in patients with ITP. Materials and Methods: Three hundred and fifty out of 491 newly diagnosed patients with ITP between the initial diagnosis ages of 6 months to 16 years were included in this retrospective, descriptive study. Patients with acute vs chronic ITP, acute vs recurrent ITP and chronic vs recurrent ITP were compared in terms of age at diagnosis, gender, initial platelet count, response rate to initial therapy, long-term outcome, and total duration of follow-up. Results: The clinical courses of the patients were determined as acute, chronic and recurrent in 63.8%, 29.1%, and 7.1%, respectively. Platelet count >20x109/L and initial diagnosis age >10 years were found to increase the probability of chronic outcome by at least two-fold. Conclusion: It is concluded that ITP in childhood is a common disease with low morbidity and mortality. In addition to the acute and chronic form, a rare recurrent form, which accounts for about 4-7% of all ITP patients, should be considered.

  5. Immune thrombocytopenic purpura in ulcerative colitis: a case report and systematic review

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    Subhash Chandra

    2014-04-01

    Full Text Available Over 100 extraintestinal manifestations are reported in ulcerative colitis (UC. A commonly reported hematological manifestation is autoimmune hemolytic anemia. On rare occasions, immune thrombocytopenic purpura (ITP has been reported with UC. The presence of thrombocytopenia can complicate the clinical scenario as the number of bloody bowel movements is an important indicator of disease activity in UC. A proposed theory for this association is antigenic mimicry between a platelet surface antigen and bacterial glycoprotein. We are reporting a case of UC and associated ITP managed successfully with anti-TNF therapy. We also performed a systemic review of case reports and a case series reporting this association.

  6. Level of IL-16 and Reticulated Platelets Percentage during the Clinical Course of Immune Thrombocytopenic Purpura in Children.

    Science.gov (United States)

    Abd El-Glil, Reem R; Assar, Effat H

    2015-01-01

    Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease with transient or persistent decrease of thrombocytes number in the blood. Cytokines play important roles in the immune regulation and are known to be deregulated in autoimmune diseases. This study aimed to investigate serum IL-16 levels in relation to reticulated platelets in children with ITP and platelet count. Twenty six children with ITP (11 with newly diagnosed ITP, 9 with persistent ITP and 6 with chronic ITP) and 12 age-matched healthy children controls were studied. Serum level of IL-16 and reticulated platelets count were assessed by Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry respectively. Serum IL-16 levels were significantly higher in patients as compared to controls (P platelets were also elevated in patients compared to controls and the increase was significant in newly diagnosed group (P platelets and platelets counts (r = -0.284, P = 0.028, r = 0.274 P = 0.25) respectively. It is concluded that IL-16 may be valuable in predicting the clinical course of pediatrics ITP. Measurement of reticulated platelets may provide significant information about thrombopoietic activity during the clinical course of ITP in children.

  7. Immune Thrombocytopenic Purpura Associated with Hepatitis A Infection in a Five-year Old Boy: A Case Report.

    Science.gov (United States)

    Urganci, N; Kilicaslan, O; Kalyoncu, D; Yilmaz, S

    2014-09-01

    Acute hepatitis A infection is usually a self-limiting disease and mostly asymptomatic in children younger than six years old. Extrahepatic autoimmune manifestations such as immune thrombocytopenic purpura (ITP) have been reported rarely in children with acute hepatitis A infection. We report herein a paediatric case with ITP which is due to hepatitis A virus infection.

  8. Plasma microRNA profiling of pediatric patients with immune thrombocytopenic purpura.

    Science.gov (United States)

    Bay, Ali; Coskun, Enes; Oztuzcu, Serdar; Ergun, Sercan; Yilmaz, Fatih; Aktekin, Elif

    2014-06-01

    Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

  9. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study.

    Science.gov (United States)

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-10-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

  10. Multiple cycles of recombinant human thrombopoietin therapy in a patient with chronic refractory idiopathic thrombocytopenic purpura.

    Science.gov (United States)

    Hua, Baolai; Zou, Nong; Wang, Shujie; Zhu, Tienan; Zhao, Yongqiang

    2005-06-01

    We describe a 41-year-old woman with chronic idiopathic thrombocytopenic purpura who received recombinant human thrombopoietin (rhTPO) therapy. rhTPO was administrated subcutaneously at a dosage of 1.0 mug/kg daily for a maximum of 14 days until the platelet count was more than 50 x 10/l. The patient received three cycles (six, 13, and eight doses each) of rhTPO, each initiated when the platelet counts was less than 10 x 10/l. The platelet count increased to above 50 x 10/l on days 5, 11 and 8, and peaked at 456 x 10/l, 130 x 10/l and 82 x 10/l on days 9, 15 and 13 in the three respective cycles, each followed by a gradual decline. The durations of platelet counts at more than 50 x 10/l in the three cycles were 13, 7 and 10 days, respectively. rhTPO was well tolerated with no adverse event observed. Antibodies to rhTPO by enzyme-linked immunosorbent assay were not detected. Our observations suggested that rhTPO could transiently increase the peripheral platelet count in patients with chronic refractory idiopathic thrombocytopenic purpura. The reasons why the peak platelet counts decreased and the duration of response shortened after successive cycles of treatment were unclear.

  11. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

    Science.gov (United States)

    Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar

    2013-04-01

    Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

  12. DNMT3B promoter polymorphism and risk of immune thrombocytopenic purpura in pediatric Egyptians.

    Science.gov (United States)

    Shaheen, Iman A; Abukhalil, Reham E; Ali, Dina K; Afifi, Rasha A

    2012-10-01

    Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between a single nucleotide polymorphism (SNP) in the promoter of DNMT3B gene and the risk for ITP in pediatric Egyptians. DNMT3B SNP was genotyped by PCR-restriction fragment length polymorphism in 71 pediatric ITP patients and 82 healthy controls matched for age and sex. The C/C wild genotype was not detected in ITP patients or in the controls. The frequencies of the T/T and C/T genotypes were 93.9 and 6.1% in the controls and 91.5 and 6.1% in ITP patients, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These results demonstrated that this SNP may not be used as a stratification marker to predict the susceptibility to childhood ITP in Egypt.

  13. Dentoalveolar trauma in a patient with chronic idiopathic thrombocytopenic purpura: a case report.

    Science.gov (United States)

    Finucane, David; Fleming, Padraig; Smith, Owen

    2004-01-01

    A case is presented of a 13-year-old boy with chronic idiopathic thrombocytopenic purpura (ITP) who sustained traumatic labial luxation of both lower central incisors, with partial alveolar fracture resulting in displacement of the labial alveolar plate. Intravenous immunoglobulin (Fleibogamma, 1 g/kg body weight x 2 days) was administered, resulting in the patient's platelet count rising from 15,000/mm3 to 70,000/mm3. Under general anesthesia, the displaced lower labial alveolus and luxated teeth were repositioned and splinted 2 days following trauma. Healing was uneventful. Subsequently, both lower central incisors became nonvital and were endodontically treated. The dental treatment of this patient with ITP is discussed in terms of emergency management, and subsequent care.

  14. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    Science.gov (United States)

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-06-08

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  15. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    Directory of Open Access Journals (Sweden)

    Maryam Maghbool

    2009-07-01

    Full Text Available Idiopathic thrombocytopenic purpura (ITP is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years. A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150x109/L or partial (platelet count between 50 and 150x109/L. We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  16. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    Directory of Open Access Journals (Sweden)

    Alex Shimanovsky

    2016-01-01

    Full Text Available Immune thrombocytopenic purpura (ITP is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases the etiology is not known, but viral illness is thought to play a role in the development of some cases of ITP. The current (2011 American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. While most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long term steroid maintenance and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV can persist in spite of standard therapy and that antiviral therapy maybe indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV infected infant and placenta. Furthermore we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV as part of the work-up for severe and refractory ITP prior to splenectomy.

  17. Common variable immunodeficiency unmasked by treatment of immune thrombocytopenic purpura with Rituximab

    DEFF Research Database (Denmark)

    Mogensen, Trine H; Jensen, Jens Magnus Bernth; Petersen, Charlotte C;

    2013-01-01

    BACKGROUND: Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs of immunod......BACKGROUND: Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs...... of immunodeficiency, this is not always recognized. Despite novel insight into the molecular immunology of common variable immunodeficiency, several areas of uncertainty remain. In addition, the full spectrum of immunological effects of the B cell depleting anti-CD20 antibody Rituximab has not been fully explored....... To our knowledge this is the first report of development of CVID in a patient with normal immunoglobulin prior to Rituximab treatment. CASE PRESENTATION: Here we describe the highly unusual clinical presentation of a 34-year old Caucasian male with treatment refractory immune thrombocytopenic purpura...

  18. Rapidly calcified all of multiple intracranial hemorrhages occurred in a patient with Chronic idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Seong Rok Han, M.D., Ph.D.

    2016-03-01

    Full Text Available We report a 38-year-old female patient with chronic idiopathic thrombocytopenic purpura (ITP who occurred in rapidly calcified all of multiple intracranial hemorrhage (ICH lesions. The patient was admitted with poor oral intake and confused mentality. Neurologic examination revealed drowsy consciousness but no motor weakness. She had been diagnosed ITP 5 years ago, however, she was not taking any medication at the time of presentation. Brain CT demonstrated that multiple ICHs, which were located in left frontal lobe, left temporal lobe and right cerebellar hemisphere. Platelet count was 10,000 cells/mm3. The patient was treated with conservative management, which included corticosteroids and platelet transfusion. Follow-up CT performed 12 days after the admission revealed that multiple ICHs were grossly resolving state. Interestingly, high attenuated lesions were seen all of multiple ICH sites, which were considered calcification. After 30 months after hemorrhage, follow-up brain CT showed prominent calcification of all of previous multiple ICH lesions. The patient was well- being state.

  19. Treatment of Infantile Chronic Idiopathic Thrombocytopenic Purpura by Auxiliary Use of Auriculo-Acupoint Pressing

    Institute of Scientific and Technical Information of China (English)

    卢燕

    2001-01-01

    @@According to the TCM theories of Meridian and Pulse-Picture, the author probed in the treatment of idiopathic thrombocytopenic purpura (ITP) with auriculo-acupoint pressing (AAP) and obtained good result. The study was reported as follows. METHODS General Materials Forty-five patients with chronic refractory of ITP selected from the 269 ITP in-patients, hospitalized from January 1991 to January 1998, were observed. They were diagnosed according to the clinical manifestations, peripheral blood picture and bone marrow examination, as well as platelet antibody test in some of them, which were all in accordance with the unified diagnostic standard of ITP in China(1). All of the patients had course of disease over half a year and their disease treated with hormone for 2-3 months ineffectively, and had hemorrhagic symptoms, such as dermatorrhagia and rhinorrhagia, with no hepatosplenomegaly, and platelet count within 8-72×109/L. The hormone therapy was withdrawn or stopped gradually in the observation period.

  20. Chronic idiopathic thrombocytopenic purpura in adult Chinese patients: a retrospective single-centered analysis of 1791 cases

    Institute of Scientific and Technical Information of China (English)

    LI Hong-qiang; ZHANG Lei; ZHAO Hui; JI Lin-xiang; YANG Ren-chi

    2005-01-01

    Background Adult chronic idiopathic thrombocytopenic purpura (ITP) is a common hematologic disease characterized by persistent thrombocytopenia. So far, there were only a few reports on adult Chinese patients with chronic ITP. This study aimed at defining the treatment outcome and prognostic factors for chronic ITP based on a large cohort of Chinese patients followed up for over 25 years at a single center.Methods The medical records of 1791 patients aged 14 years or older who were diagnosed as having chronic ITP at our hospital from 1974 to 1999 were retrospectively analyzed.Conclusions Adult Chinese chronic ITP patients can have long-term remission after steroid therapy and splenectomies. Primary steroid refractoriness is a prognostic factor predicting poor subsequent response to a splenectomy.

  1. Clinical efficacy of lower dose rituximab for chronic refractory immune thrombocytopenic purpura%小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床观察

    Institute of Scientific and Technical Information of China (English)

    李燕; 王晓敏; 毛敏; 张晓燕; 富玲; 艾合买江; 张莲兴

    2012-01-01

    目的 探讨小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症(ITP)的疗效及安全性.方法 研究纳入20例复发难治性ITP患者,给予利妥昔单抗100 mg静脉滴注,每周1次,连用4周,动态观察血常规、肝肾功能及凝血功能.采用流式细胞术检测治疗前后CD3+、CD4+、CD8+、CD19+淋巴细胞数.免疫比浊法定量检测治疗前后血清免疫球蛋白(IgG、lgM、IgA)水平.用ELISA方法检测血小板膜糖蛋白抗体.治疗前后各项检测指标比较采用配对t检验.结果 治疗后中位起效时间为18d,PLT达峰值时间为(24±7)d.治疗后PLT[(124±106)×109/L]显著高于治疗前[(13±5)×109/L](P<0.01).11例(55%)患者达完全反应(CR),4例(20%)有效(R),5例(25%)无效(NR).中位疗效持续时间为8(5~23)个月.治疗前后外周血WBC、HGB、血清免疫球蛋白以及CD3+、CD4+、CD8+淋巴细胞数无明显变化,CD19+淋巴细胞数治疗后[(50.53±29.11)×106/L]较治疗前[(125.65±14.12)×106/L]明显下降(P<0.01).3例患者治疗前血小板自身抗体检测阳性,治疗后均为阴性.1例患者在首次输注利妥昔单抗后发生轻微不良反应.结论 小剂量利妥昔单抗是一种治疗复发难治性ITP安全有效的药物,但其最佳用药方案、长期疗效以及不良反应有待临床进一步观察验证.%Objective To investigate the efficacy and safety as well as the effects of lower dose of rituximab on B-lymphocytes,serum immunoglobulin,and platelet glycoprotein-specific antibodies in patients with chronic refractory immune thrombocytopenic purpura (ITP).Methods Twenty chronic refractory ITP patients,median age 47(20 to 60) years old,received intravenous rituximab at the dose of 100mg once weekly for 4 consecutive weeks.Laboratory studies included complete blood cell count,regular monitoring of liver and kidney functions,blood coagulation and serum concentrations of IgG,IgM and IgA. CD3 +,CD4 +,CD8 +,CD19 +,CD20 + cell

  2. A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

    Institute of Scientific and Technical Information of China (English)

    Hong Wei; Xinchun Ding; Jiangong Ren; Ka Liu; Pingping Tan; Daquan Li; Runlin Z.Ma

    2008-01-01

    Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im-munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura (ITP) has not been fullyunderstood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or plateletdestruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into theBalb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini-mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h (6 days). Final homeostasis reached atapproximately 408 h (17 days), following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed andcompared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration ofmRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be-tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when plateletnumber reached the maximum (144 h). In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleentissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Ourresults provided the supportive evidence that expression of the above seven genes are more related to negative regulation of plateletnumber in spleen tissue, at least in the model animals.

  3. The etiology of childhood immune thrombocytopenic purpura: how complex is it?

    Science.gov (United States)

    Chanock, Stephen

    2003-12-01

    Recent developments in genomics and basic immunology have provided a new set of tools for investigation into the etiology and treatment of childhood immune thrombocytopenia purpura (ITP). The genomic revolution is generating a catalog of germ-line common genetic variants, some of which could influence the susceptibility or outcome of ITP. Similarly, in vitro analyses and animal models have been employed to probe the basic alterations underlying ITP. The emergence of a more refined understanding of complex diseases such as ITP has important implications for prevention, therapy, and follow-up. The relative contribution of the genetic component and its interaction with the strong environmental stimulus, such as an acute, antecedent viral infection, remains to be determined.

  4. Idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    L Kayal

    2014-01-01

    Full Text Available Idiopathic thrombocytopenic purpura (ITP is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production, and increased splenic sequestration. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. We present a case report on ITP with clinical presentation, diagnosis and management.

  5. 儿童特发性血小板减少性紫癜急性转慢性危险因素分析%Risk factors of acute idiopathic thrombocytopenic purpura developing into chronic idiopathic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    王缉干; 罗建明

    2012-01-01

    目的 探讨影响小儿急性特发性血小板减少性紫癜(AITP)发展成慢性特发性血小板减少性紫癜(CITP)的危险因素.方法 选择2006年5月至2010年4月于广西医科大学一附院诊断AITP住院患儿138例,对患儿临床表现、实验室检查、治疗方案等16个相关因素分别进行单因素成组对照研究.对有意义的单因素,再运用非条件Logistic多因素回归模型分析,以期找到有意义的因素.结果 病程(患儿起病至治疗时间)、ORh(D)+型血、用含有大剂量丙种球蛋白的治疗方案、血小板上升正常时间都是影响AITP患儿转为慢性的主要因素,而与发病年龄、治疗初用血小板、血小板开始回升时间、性别、有无前驱显性感染、治疗前血小板数、血小板平均体积、血小板平均分布系数、骨髓巨核细胞数、幼稚巨核细胞数、颗粒型巨核细胞数、有无幼稚淋巴细胞数无关.结论 AITP患儿早期治疗时用有大剂量丙种球蛋白的治疗方案是改善预后的关键,治疗时血小板回升正常时间晚、ORh(D)+血型(相对于A和B血型)是转为慢性的高危因素.%Objectives To investigate the risk factors for children with acute idiopathic thrombocytopenic purpura (AITP) developing into chronic idiopathic thrombocytopenic purpura (CITP). Methods A total of 138 patients with AITP from May 2006 to April 2010 in the First Affiliated Hospital of Guangxi Medical University were Selected and telephoned for retrospective analysis. The 16 related factors, including clinical presentation, laboratory tests and treatment programs, were performed single case-control study. For those significant single factors, multi-factor non-conditional Logistic regression analysis was used to find meaningful factors. Results The main influencing factors were the onset-to-treatment time,0 Rh (D) + type blood, treatment with gamma globulin and platelets increasing to normal time. The age of onset, early treatment

  6. DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

    Science.gov (United States)

    Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

    2012-12-10

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

  7. Thrombocytopenic purpura as initial presentation of acute hepatitis A.

    Science.gov (United States)

    Scott, Julius Xavier; Gnananayagam, Ebor Jacob; Gupta, Sanjay; Simon, Anna; Mukhopadhya, Ashish

    2003-01-01

    Extrahepatic immune manifestations are rare in hepatitis A virus infection. We report a 4 1/2-year-old girl who presented with thrombocytopenic purpura as initial manifestation of hepatitis A virus infection. She responded to steroid therapy.

  8. Idiopathic thrombocytopenic purpura: laboratory diagnosis and management

    Directory of Open Access Journals (Sweden)

    Alvina Alvina

    2016-02-01

    Full Text Available Idiopathic thrombocytopenic purpura (ITP or immune thrombocytopenic purpura is a disease characterized by low platelet count (<150,000/ìL caused by autoantibody-mediated platelet destruction and the absence of other causes of thrombocytopenia. Acute primary ITP is more common in children 2-6 years of age, with similar incidence between males and females, while the chronic form is usually encountered in adults with median age of 40-45 years. The clinical signs of ITP are purpura, ecchymosis, petechiae and gastrointestinal tract bleeding, gingival bleeding, epistaxis, and urinary tract bleeding. Spontaneous mucosal, intracranial, and gastrointestinal hemorrhage may occur at platelet counts of <10000/ìL. To date, the diagnosis of ITP is still arrived at by exclusion, i.e. by elimination of other causes of thrombocytopenia. The diagnosis of ITP also requires a medical history (anamnesis, physical examination, platelet count, and examination of a peripheral blood smear. The latter examination in ITP shows low numbers of normal-sized platelets, occasionally also giant platelets, while erythrocytes and leukocytes have a normal morphology. The bone marrow is usually normal or shows increased megakaryocytes. Assessment of antithrombocyte antibody may assist in establishing the diagnosis of ITP. Management of ITP is based on platelet count and severity of bleeding. Treatment is aimed at interfering with antibodies that damage the platelets, by inhibiting the functions of macrophage Fcã receptors and decreasing the production of antiplatelet antibodies. Thrombopoietin (TPO receptor agonists including eltrombopag and romiplostim have offered an important new option in treating ITP.

  9. Cesarean Section and Chronic Immune Disorders

    DEFF Research Database (Denmark)

    Sevelsted, Astrid; Stokholm, Jakob; Bønnelykke, Klaus;

    2015-01-01

    OBJECTIVES: Immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have shown a parallel increase in prevalence during recent decades in westernized countries. The rate of cesarean delivery has also increased in this period and has been associated...... with the development of some of these diseases. METHODS: Mature children born by cesarean delivery were analyzed for risk of hospital contact for chronic immune diseases recorded in the Danish national registries in the 35-year period 1977-2012. Two million term children participated in the primary analysis. We......, or celiac disease. CONCLUSIONS: Cesarean delivery exemplifies a shared environmental risk factor in early life associating with several chronic immune diseases. Understanding commonalities in the underlying mechanisms behind chronic diseases may give novel insight into their origin and allow prevention....

  10. Thrombophilia in patients with chronic immune thrombocytopenia.

    Science.gov (United States)

    Wong, Raymond S M; Bakshi, Kalpana; Brainsky, Andres

    2015-01-01

    An increased risk of thromboembolic events among patients with chronic immune thrombocytopenia has been reported but is still not fully understood. A thrombophilia panel (factors suspected/known to denote a thrombophilic state or indicate activation of the clotting cascade) was measured in previously treated patients with chronic immune thrombocytopenia enrolled in an eltrombopag trial to assess potential thrombophilia risk markers. Of 167 patients, 136 (81%) had abnormal levels of at least 1 known or suspected thrombosis risk marker or coagulation cascade activation marker. Six patients reported thromboembolic events, and all of these patients had at least two abnormal analytes in the thrombophilia panel. The presence of multiple baseline thrombophilia risk markers support the theory that chronic immune thrombocytopenia is a pro-thrombotic disease.

  11. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. 1946.

    Science.gov (United States)

    2016-01-01

    This paper, by one of the legends of hematology, William Dameshek, and his colleague Edward Miller, is from the inaugural issue of Blood. By studying bone marrow specimens from controls, patients with acute or chronic immune thrombocytopenia, or patients with other thrombocytopenic disorders, the authors concluded that, in idiopathic thrombocytopenic purpura (ITP), production of platelets from megakaryocytes is defective, even while marrow megakaryocytes are greatly increased in number. This defect resolved after splenectomy. The authors appropriately credit E. Frank with having proposed defective platelet production from megakaryocytes in ITP in 1915. The idea that platelet production was defective in ITP was superseded or ignored for decades, but it has now been validated by the therapeutic effectiveness of the thrombopoietin mimetics in ITP.

  12. Dieulafoy Lesion in the Ascending Colon Presenting with Gastrointestinal Bleeding and Severe Anemia Complicated by a Coexisting Severe Resistant Chronic Idiopathic Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2014-01-01

    Full Text Available Background. GI (gastrointestinal bleeding can be due to a variety of etiologies ranging from being common like bleeding peptic ulcer disease or esophageal varices. One of the rarely documented causes is the Dieulafoy lesion which is known as an abnormally large ectatic artery that penetrates the gut wall, occasionally eroding through the mucosa causing massive bleeding. In addition to that, we refer to the uncommon presentation of Dieulafoy lesion itself as it is well known to be found in the stomach, esophagus, duodenum, and jejunum but not the ascending colon as in our case. The patient had a coexisting ITP (idiopathic thrombocytopenic purpura that was resistant to different therapies. Case Report. We report a case of a 48-year-old Egyptian female known for chronic ITP resistant to treatment. The patient presented with bright red bleeding per rectum and severe life threatening anemia. Endoscopic study showed a Dieulafoy lesion. Endoscopic clipping was successful in controlling the bleeding. Conclusion. Dieulafoy lesion is a rare reason for GI bleeding and can present in common or unexpected places. Also extreme caution should be used in patients with bleeding tendency due to different reasons, like ITP in our case.

  13. Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

    Directory of Open Access Journals (Sweden)

    Haiyan Lang

    2016-07-01

    Conclusion: According to the syndrome differentiation criteria for disease-syndrome combined model of ITP, the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model. It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

  14. Immune regulation during chronic visceral leishmaniasis.

    Science.gov (United States)

    Faleiro, Rebecca J; Kumar, Rajiv; Hafner, Louise M; Engwerda, Christian R

    2014-07-01

    Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.

  15. A disease-specific measure of health-related quality of life for use in adults with immune thrombocytopenic purpura: Its development and validation

    Directory of Open Access Journals (Sweden)

    McMillan Robert

    2007-02-01

    Full Text Available Abstract Background No validated disease-specific measures are available to assess health-related quality of life (HRQoL in adult subjects with immune thrombocytopenic purpura (ITP. Therefore, we sought to develop and validate the ITP-Patient Assessment Questionnaire (ITP-PAQ for adult subjects with ITP. Methods Information from literature reviews, focus groups with subjects, and clinicians were used to develop 50 ITP-PAQ items. Factor analyses were conducted to develop the scale structure and reduce the number of items. The final 44-item ITP-PAQ, which includes ten scales [Symptoms (S, Bother-Physical Health (B, Fatigue/Sleep (FT, Activity (A, Fear (FR, Psychological Health (PH, Work (W, Social Activity (SA, Women's Reproductive Health (RH, and Overall (QoL], was self-administered to adult ITP subjects at baseline and 7–10 days later. Test-retest reliability, internal consistency reliability, construct and known groups validity of the final ITP-PAQ were evaluated. Results Seventy-three subjects with ITP completed the questionnaire twice. Test-retest reliability, as measured by the intra-class correlation, ranged from 0.52–0.90. Internal consistency reliability was demonstrated with Cronbach's alpha for all scales above the acceptable level of 0.70 (range: 0.71–0.92, except for RH (0.66. Construct validity, assessed by correlating ITP-PAQ scales with established measures (Short Form-36 v.1, SF-36 and Center for Epidemiologic Studies Depression Scale, CES-D, was demonstrated through moderate correlations between the ITP-PAQ SA and SF-36 Social Function scales (r = 0.67, and between ITP-PAQ PH and SF-36 Mental Health Scales (r = 0.63. Moderate to strong inter-scale correlations were reported between ITP-PAQ scales and the CES-D, except for the RH scale. Known groups validity was evaluated by comparing mean scores for groups that differed clinically. Statistically significant differences (p Conclusion Results provide preliminary evidence of

  16. A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

    Science.gov (United States)

    Viner, Maya; Murakhovskaya, Irina

    2016-11-24

    Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

  17. The potential role of thrombopoietin in idiopathic thrombocytopenic purpura

    NARCIS (Netherlands)

    von dem Borne, A; Folman, C; van den Oudenrijn, S; de Jong, S; de Haas, M

    2002-01-01

    Thrombopoietin (TPO) plays a central role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), as it does in other immune-mediated thrombocytopenias. Because TPO is bound and internalized by platelets, it is destroyed together with platelets at an accelerated rate in the macrophage syst

  18. 病毒感染与免疫性血小板减少性紫癜的临床观察%Clinical observation of the relationship between immune thrombocytopenic purpura and virus infection

    Institute of Scientific and Technical Information of China (English)

    张永卓

    2013-01-01

    Objective To investigate the relationship between immune thrombocytopenic purpura (ITP) and virus infection.Methods A retrospectively analysis was based on the clinical records.ELSIA tests of EBV and CMV antibody were performed at 50 children suffered from ITP.The clinical characteristics and therapeutic effects in viral infection group and non-viral infection group were compared.Results Thirty-eight children in 50 cases who suffered from ITP were infected by EBV or CMV.Between viral infection group and non viral infection group,there was no significant difference in clinical features,hemoglobin and platelet (P > 0.05).But,it showed that the effects of viral infection group were better than those of non viral infection group at the time of two months and six months after treatment (P < 0.05).There were 18 cases ineffective in the viral infection group for six months treatment.There was the higher chronic tendency incidence in viral infection group (47.3%) than that in the non viral infection group (8.3%).Conclusions Most ITP patients infected by virus.Virus associated ITP had poor treatment effect and is easy to prolong course.%目的 探讨免疫性血小板减少性紫癜(ITP)与病毒感染的关系.方法 回顾性分析50例ITP儿童的临床资料,采用ELISA法检测50例ITP患儿血清病毒抗体(EB病毒及巨细胞病毒等),比较病毒抗体检测在病毒感染组及非病毒感染组ITP患儿中的临床特点及治疗效果.结果 病毒血清学检测:病毒感染38例,非病毒感染12例.病毒感染组与非病毒感染组比较:①两组临床表现、Hb及血小板计数比较差异均无统计学意义(P>0.05);②治疗后2个月效果比较差异有统计学意义(P<0.05),病毒感染组初始疗效较非病毒感染组治疗有效率低;③治疗后6个月两组疗效比较差异有统计学意义(P<0.05),治疗后6个月病毒感染组无效18例(47.4%),且呈慢性倾向,明显高于非病毒感染组(8.3%).结论

  19. Innate immunity and chronic immune activation in HCV/HIV-1 co-infection.

    Science.gov (United States)

    Gonzalez, Veronica D; Landay, Alan L; Sandberg, Johan K

    2010-04-01

    Innate immune responses are critical in the defense against viral infections. NK cells, myeloid and plasmacytoid dendritic cells, and invariant CD1d-restricted NKT cells mediate both effector and regulatory functions in this early immune response. In chronic uncontrolled viral infections such as HCV and HIV-1, these essential immune functions are compromised and can become a double edged sword contributing to the immunopathogenesis of viral disease. In particular, recent findings indicate that innate immune responses play a central role in the chronic immune activation which is a primary driver of HIV-1 disease progression. HCV/HIV-1 co-infection is affecting millions of people and is associated with faster viral disease progression. Here, we review the role of innate immunity and chronic immune activation in HCV and HIV-1 infection, and discuss how mechanisms of innate immunity may influence protection as well as immunopathogenesis in the HCV/HIV-1 co-infected human host.

  20. A Remarkable Improvement of Patients with Idiopathic Thrombocytopenic Purpura after appendectomy including Carcinoid tumor

    OpenAIRE

    Hamidreza Alizadeh-Otaghvar; Saeedeh Firoozbakht; Sahar Montazeri; Samaneh Khazraie; Marjan Bani Ahmad; Maryam Hajiloo

    2011-01-01

    The assistance of chronic idiopathic thrombocytopenic purpura and appendiceal carcinoid tumor is so rare and has not been reported before .we present here in a 11 year old boy that is the known case of chronic idiopathic thrombocytopenic purpura (with the platelet count of 20000 when admitted). He reffered due to anorexia, pain and tenderness of right lower quadrant of abdomen and vomiting. He also had leukocytosis and abdominal free fluid in sonographic report. These findings suggested the d...

  1. Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling

    Science.gov (United States)

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0388 TITLE: Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling ...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Subgrouping Chronic Fatigue Syndrome Patients By Genetic And Immune Profiling 5b. GRANT...studying the results. We have finished the DNA isolation and anticipate the HLA testing to be completed this upcoming year. We want to interrogate the

  2. Polyphasic innate immune responses to acute and chronic LCMV infection: Innate immunity to acute & chronic viral infection

    OpenAIRE

    Norris, Brian A; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after ...

  3. Immune regulation in chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou;

    2016-01-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion...... and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs....... Thus, the major immune players during chronic HCV infection are characterized by a decrease of cytotoxic function and increase of inhibitory functions. This may be an approach to diminish intrahepatic and systemic inflammation. Finally, there has been increasing awareness of regulatory functions...

  4. Extrahepatic immune related manifestations in chronic hepatitis C virus infection.

    Science.gov (United States)

    Tampaki, Maria; Koskinas, John

    2014-09-21

    The association of chronic hepatitis C with immune related syndromes has been frequently reported. There is a great range of clinical manifestations affecting various systems and organs such as the skin, the kidneys, the central and peripheral nervous system, the musculoskeletal system and the endocrine glands. Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C, the exact pathogenesis is not always clear. They have been often associated with mixed cryoglobulinemia, a common finding in chronic hepatitis C, cross reaction with viral antigens, or the direct effect of virus on the affected tissues. The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes, their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

  5. Latent viral immune inflammatory response model for chronic multisymptom illness.

    Science.gov (United States)

    Maloney, Sean R; Jensen, Susan; Gil-Rivas, Virginia; Goolkasian, Paula

    2013-03-01

    A latent viral immune inflammatory response (LVIIR) model is presented which integrates factors that contribute to chronic multisymptom illness (CMI) in both the veteran and civilian populations. The LVIIR model for CMI results from an integration of clinical experience with a review of the literature in four distinct areas: (1) studies of idiopathic multisymptom illness in the veteran population including two decades of research on Gulf War I veterans with CMI, (2) new evidence supporting the existence of chronic inflammatory responses to latent viral antigens and the effect these responses may have on the nervous system, (3) recent discoveries concerning the role of vitamin D in maintaining normal innate and adaptive immunity including suppression of latent viruses and regulation of the immune inflammatory response, and (4) the detrimental effects of extreme chronic repetitive stress (ECRS) on the immune and nervous systems. The LVIIR model describes the pathophysiology of a pathway to CMI and presents a new direction for the clinical assessment of CMI that includes the use of neurological signs from a physical exam, objective laboratory data, and a new proposed latent viral antigen-antibody imaging technique for the peripheral and central nervous system. The LVIIR model predicts that CMI can be treated by a focus on reversal of immune system impairment, suppression of latent viruses and their antigens, and healing of nervous system tissue damaged by chronic inflammation associated with latent viral antigens and by ECRS. In addition, the LVIIR model suggests that maintaining optimal serum 25 OH vitamin D levels will maximize immune system suppression of latent viruses and their antigens and will minimize immune system inflammation. This model also emphasizes the importance of decreasing ECRS to improve immune system function and to minimize nervous system injury from excess serum glucocorticoid levels. The proposed model supports growing evidence that increasing

  6. Subgrouping Chronic Fatigue Syndrome Patients By Genetic and Immune Profiling

    Science.gov (United States)

    2015-12-01

    phospho- flow , flow cytometry, pico-green, quality control, Chronic Fatigue Immune Dysfunction, genetic, immune, infectious disease 16. SECURITY...instrumentation, materials , or assay operation), we will employ the mean response from the prior batch as a covariate and also account for the fact that the...of each derived phenotype as a binary outcome variable in a logistic regression structured per model E1. BODY (HLA Typing): Analyses to date

  7. The analysis of factors of acute Idiopathic thrombocytopenic purpura conversing to chronic Idiopathic thrombocytopenic purpura in children%儿童特发性血小板减少性紫癜急性转慢性危险因素分析

    Institute of Scientific and Technical Information of China (English)

    周丹; 杨萍; 田立新; 冯玉兰; 宋丽琼

    2013-01-01

    Objective:To analyze the factors of cute Idiopathic thrombocytopenic purpura (AITP) conversing to chronic Idiopathic thrombocytopenic purpura (CITP). Methods:Choosed 156 children of AITP to analyze by lab, diagnosis and treatment, effect and prognosis. Methods:There were 12 index having difference, among these 2 index were continuous variable (weight, peak platelet). Implement multi-factor analysis of these 12 factors, and screened medical history, age, low count of WBC, weight,high count of marrow megakaryocyte and peak of platelet. Conclusion:Dignosising AITP patients with count of marrow megakaryocyte, peak of platelet to determine prognosis is effective.%目的:分析致使 AITP(即为:儿童特发性急性的血小板减少性紫癜)转变为 CITP(即为:儿童特发性慢性的血小板减少性紫癜)的相关因素。方法:随机对156例患儿分组,行调查分析、实验室分析、诊治方法分析、诊治效果分析、机体预后情况分析。结果:在所有因素指标之中,12项指标存在显著差异,P<0.05,其中,有2项是连续型变量,包括体重(生病之时)、血小板峰值(诊治以后),对存在显著意义且经单因素分析的12项因素实施多因素分析(Logistic非条件回归模型),各危险因素分别为诊治前较长的病史、年龄大(发病之时)、白细胞计数在病初阶段降低或者正常、体重于发病时较大、骨髓巨核细胞于病初阶段数目高、血小板峰值于诊治后降低。结论:在初诊AITP病儿之时,检查骨髓巨核细胞,并于诊治中对血小板最大值予以观察,对判断预后很有价值,对AITP预后的改善有利的因素即为早确诊、早诊治。

  8. Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura

    Science.gov (United States)

    Takahashi, Tohru; Maruyama, Yumiko; Saitoh, Mayuko; Itoh, Hideto; Yoshimoto, Mitsuru; Tsujisaki, Masayuki; Nakayama, Masato

    2016-01-01

    A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved. PMID:27746431

  9. The influence of chronic stress on T cell immunity

    OpenAIRE

    Sommershof, Annette

    2010-01-01

    Chronic environmental and psychological stress has long been suspected to increase the susceptibility and outcome of numerous infectious and inflammatory diseases. The release of neurotransmitters (catecholamines) and adrenal hormones (glucocorticoids) has been well documented as the basis for a connection between the central nervous system and peripheral components of the immune system. Glucocorticoids, the end products of stress-induced neuroendocrine pathways and the hypothalamic-pituitary...

  10. Lung transplantation: chronic allograft dysfunction and establishing immune tolerance.

    Science.gov (United States)

    Gracon, Adam S A; Wilkes, David S

    2014-08-01

    Despite significant medical advances since the advent of lung transplantation, improvements in long-term survival have been largely unrealized. Chronic lung allograft dysfunction, in particular obliterative bronchiolitis, is the primary limiting factor. The predominant etiology of obliterative bronchiolitis involves the recipient's innate and adaptive immune response to the transplanted allograft. Current therapeutic strategies have failed to provide a definitive treatment paradigm to improve long-term outcomes. Inducing immune tolerance is an emerging therapeutic strategy that abrogates allograft rejection, avoids immunosuppression, and improves long-term graft function. The aim of this review is to discuss the key immunologic components of obliterative bronchiolitis, describe the state of establishing immune tolerance in transplantation, and highlight those strategies being evaluated in lung transplantation.

  11. Interleukin-17 and innate immunity in infections and chronic inflammation.

    Science.gov (United States)

    Isailovic, Natasa; Daigo, Kenji; Mantovani, Alberto; Selmi, Carlo

    2015-06-01

    Interleukin 17 (IL-17) includes several cytokines among which IL-17A is considered as one of the major pro-inflammatory cytokine being central to the innate and adaptive immune responses. IL-17 is produced by unconventional T cells, members of innate lymphoid cells (ILCs), mast cells, as well as typical innate immune cells, such as neutrophils and macrophages located in the epithelial barriers and characterised by a rapid response to infectious agents by recruiting neutrophils as first line of defence and inducing the production of antimicrobial peptides. Th17 responses appear pivotal in chronic and acute infections by bacteria, parasites, and fungi, as well as in autoimmune and chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and psoriatic arthritis. The data discussed in this review cumulatively indicate that innate-derived IL-17 constitutes a major element in the altered immune response against self antigens or the perpetuation of inflammation, particularly at mucosal sites. New drugs targeting the IL17 pathway include brodalumab, ixekizumab, and secukinumab and their use in psoriatic disease is expected to dramatically impact our approach to this systemic condition.

  12. A Case Associated with Comorbidities Among Cerebral Infarction, Idiopathic Thrombocytopenic Purpura, and Triple X Syndrome

    Directory of Open Access Journals (Sweden)

    Hanjun Kim

    2014-06-01

    Full Text Available A 46-year-old female presented to the emergency room due to the chief complaint of left-sided weakness. By imaging study, she was diagnosed with cerebral infarction. Thrombolytic and antiplatelet agents were not considered due to the “golden hour” for treatment having passed and a low platelet count. The peripheral blood smear, bone marrow biopsy, and aspirate findings were consistent with immune thrombocytopenic purpura. The chromosome analysis revealed the 47,XXX karyotype. To the best of our knowledge, this is the first case report associated with the comorbidities of cerebral infarction, idiopathic thrombocytopenic purpura, and triple X syndrome.

  13. Epithelial NEMO links innate immunity to chronic intestinal inflammation.

    Science.gov (United States)

    Nenci, Arianna; Becker, Christoph; Wullaert, Andy; Gareus, Ralph; van Loo, Geert; Danese, Silvio; Huth, Marion; Nikolaev, Alexei; Neufert, Clemens; Madison, Blair; Gumucio, Deborah; Neurath, Markus F; Pasparakis, Manolis

    2007-03-29

    Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease. The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis-acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides. However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF-kappaB, a master regulator of pro-inflammatory responses, functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gut microflora. Intestinal epithelial-cell-specific inhibition of NF-kappaB through conditional ablation of NEMO (also called IkappaB kinase-gamma (IKKgamma)) or both IKK1 (IKKalpha) and IKK2 (IKKbeta)-IKK subunits essential for NF-kappaB activation-spontaneously caused severe chronic intestinal inflammation in mice. NF-kappaB deficiency led to apoptosis of colonic epithelial cells, impaired expression of antimicrobial peptides and translocation of bacteria into the mucosa. Concurrently, this epithelial defect triggered a chronic inflammatory response in the colon, initially dominated by innate immune cells but later also involving T lymphocytes. Deficiency of the gene encoding the adaptor protein MyD88 prevented the development of intestinal inflammation, demonstrating that Toll-like receptor activation by intestinal bacteria is essential for disease pathogenesis in this mouse model. Furthermore, NEMO deficiency sensitized epithelial cells to tumour-necrosis factor (TNF)-induced apoptosis, whereas TNF receptor-1 inactivation inhibited intestinal inflammation, demonstrating that TNF receptor-1 signalling is crucial for disease induction. These findings demonstrate that a primary NF-kappaB signalling defect in intestinal epithelial cells disrupts immune homeostasis in the gastrointestinal tract

  14. Immune and hemorheological changes in Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Ashton Kevin J

    2010-01-01

    Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. Methods Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16- and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. Results CFS patients (n = 10 had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56brightCD16- NK phenotypes in comparison to healthy controls (n = 10. However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar between the two groups. Conclusion These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients.

  15. The Role of Innate Immunity and Aeroallergens in Chronic Rhinosinusitis.

    Science.gov (United States)

    London, Nyall R; Tharakan, Anuj; Ramanathan, Murugappan

    2016-01-01

    Allergy has been inferred to contribute to the pathophysiology of chronic rhinosinusitis (CRS) although this role is controversial and the mechanism is debated. Furthermore, the role of aeroallergens in CRS is poorly defined and has been postulated to contribute to CRS through direct penetration in the sinuses or downstream systemic consequences. Common aeroallergens implicated in chronic rhinosinusitis include air pollution/second hand smoke, dust mite and pollen [1,2,3]. One emerging potential mechanism whereby aeroallergens contribute to CRS is through sinonasal epithelial barrier disruption (fig. 1). Characterization of cytokine disruption of sinonasal epithelial cell barrier has been described including interleukin (IL)-4 and IL-13, as well as aeroallergens such as house dust mite and cigarette smoke. Recent results have demonstrated severe barrier disruption in response to direct application of either particulate matter (PM) or house dust mite (HDM) to sinonasal epithelial cells. Sinonasal epithelial barrier disruption may contribute to CRS by enabling the perpetual and chronic exposure of inflammatory allergens and stimuli. The sinonasal epithelial barrier plays a significant role in innate immune host defense. Mechanisms of innate immune defense include pattern recognition receptors (PRRs), secreted endogenous antimicrobials and inflammatory cytokines that aid in repair mechanisms including IL-33. Here we discuss recent evidence implicating aeroallergens and dysregulated host innate immune responses in the development of CRS. 1Fig. 1. Aeroallergens and inflammatory stimuli disrupt sinonasal epithelial barrier function. These agents act to destabilize the barrier through stimulating endocytosis and destruction of cell junction proteins via oxidative stress and MyD88-dependent mechanisms. Furthermore, aeroallergens and inflammatory stimuli induce secretion of IL-25, IL-33, and TSLP from sinonasal epithelial cells.F01.

  16. Celiac Disease Presenting with Immune Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Hakan Sarbay

    2017-01-01

    Full Text Available Celiac disease (CD is an immunological disorder. Clinical manifestations occur as a result of intestinal mucosa damage and malabsorption. CD is also associated with extraintestinal manifestations and autoimmune disorders. The coexistence of CD and autoimmune diseases has been described before. In this article, a patient with CD presenting with thrombocytopenia is discussed.

  17. The paradox of chronic neuroinflammation, systemic immune suppression and autoimmunity after traumatic chronic spinal cord injury

    OpenAIRE

    Schwab, Jan M.; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G.

    2014-01-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the “immune privileged/specialized” milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of “SCI disease” ...

  18. Acupuncture and Immune Function in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized, Controlled Study

    Science.gov (United States)

    Lee, Shaun Wen Huey; Liong, Men Long; Yuen, Kah Hay; Krieger, John N

    2014-01-01

    Objective The immune system has been implicated as one mechanism underlying the benefits of acupuncture therapy. Evidence suggests that acupuncture can ameliorate symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but the association between clinical response and the immune system has not been investigated. Design/Setting We investigated 12 CP/CPPS patients participating in a prospective randomized clinical trial comparing acupuncture versus sham acupuncture for effects on cellular immunity. Blood samples were taken before the first needling and after the last of 20 treatment sessions (week 10). Patients also completed questionnaires examining their CP/CPPS symptoms and mood status at the baseline and end of study visits. Results At the end of study 8 of 12 participants (67%) were classified as treatment responders, 4 participants each from the acupuncture and sham groups. The acupuncture group averaged a 5% increase in natural killer cell levels compared to corresponding sham (-13%; p=0.03). Similarly, patients randomized to acupuncture reported a reduction in other white blood cell parameters examined, supporting the possibility that immunity might be important in the pathophysiology of CP/CPPS. Conclusions The specific effect of acupuncture on CP/CPPS remains unclear. Further research is warranted to examine the mechanisms by which acupuncture therapy may improve clinical symptoms in patients with CP/CPPS. PMID:25453515

  19. Basal inflammation and innate immune response in chronic multisite musculoskeletal pain

    NARCIS (Netherlands)

    Generaal, E.; Vogelzangs, N.; MacFarlane, G.J.; Geenen, R.; Smit, J.H.; Dekker, J.; Penninx, B.W.J.H.

    2014-01-01

    Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain.

  20. Disruption of immune regulation by microbial pathogens and resulting chronic inflammation.

    Science.gov (United States)

    Barth, Kenneth; Remick, Daniel G; Genco, Caroline A

    2013-07-01

    Activation of the immune response is a tightly regulated, coordinated effort that functions to control and eradicate exogenous microorganisms, while also responding to endogenous ligands. Determining the proper balance of inflammation is essential, as chronic inflammation leads to a wide array of host pathologies. Bacterial pathogens can instigate chronic inflammation via an extensive repertoire of evolved evasion strategies that perturb immune regulation. In this review, we discuss two model pathogens, Mycobacterium tuberculosis and Porphyromonas gingivalis, which efficiently escape various aspects of the immune system within professional and non-professional immune cell types to establish chronic inflammation.

  1. Patient-reported treatment burden of chronic immune thrombocytopenia therapies

    Directory of Open Access Journals (Sweden)

    Brown T

    2012-03-01

    Full Text Available Abstract Background Chronic immune thrombocytopenia (ITP is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy. This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. Methods A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress, and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS, intravenous immunoglobulin (IVIg, anti-D immunoglobulin (anti-D, rituximab (RT, and splenectomy (SPL, as well as for other patient-referenced therapies (captured as "other". Results The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71, and 68% reported a typical low platelet count of P P P P Conclusions Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

  2. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Science.gov (United States)

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  3. Esplenectomia vídeo-laparoscópica para púrpura trombocitopênica imune: técnica e resultados Laparoscopic splenectomy for immune thrombocytopenic purpura: technique and results of a prospective study

    Directory of Open Access Journals (Sweden)

    Ricardo Zorrón

    2004-08-01

    ópica é segura e efetiva, tornando-se o tratamento de escolha para PTI com indicação cirúrgica.BACKGROUND: Immune thrombocytopenic purpura (ITP is a common indication for splenectomy. In order to evaluate the results of Laparoscopic Splenectomy, 17 patients with ITP were submitted to this procedure in a prospective study. METHODS: Using three trocars through a posterior approach and simple inabsorbable ligatures, without using hemoclips and vascular stapplers, splenectomy was carried out in a prospective series of 17 patients. RESULTS: All patients were successfully managed laparoscopically, with no conversion to open surgery. Complications ocurred in three patients: one wound haematoma, one residual splenic tissue requiring reoperation, and one pancreatic pseudocyst that was treated by conservative measures. An additional fourth trocar was needed in four patients. Mean operative time was 132.9min, mean postoperative stay was 2.53 days. Intraoperative platelet transfusion was needed in two patients (11.8% and accessory spleen was detected in four (23.5%. Favourable sustained response to splenectomy was obtained in 13 patients (76.5%, with partial or no response in four (23.5%. CONCLUSION: Careful anatomical dissection technique and search for accessory tissue is needed to avoid splenosis and therapy failure. Detection of accessory spleens by this method is precise and reliable. Patients with PTI have the same remission rates of open surgery, with less complications and shortened postoperative stay. The results suggest that Laparoscopic Splenectomy is effective and safe, and has become the golden standard for the treatment of ITP with surgical indication.

  4. A Remarkable Improvement of Patients with Idiopathic Thrombocytopenic Purpura after appendectomy including Carcinoid tumor

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    Hamidreza Alizadeh-Otaghvar

    2011-09-01

    Full Text Available The assistance of chronic idiopathic thrombocytopenic purpura and appendiceal carcinoid tumor is so rare and has not been reported before .we present here in a 11 year old boy that is the known case of chronic idiopathic thrombocytopenic purpura (with the platelet count of 20000 when admitted. He reffered due to anorexia, pain and tenderness of right lower quadrant of abdomen and vomiting. He also had leukocytosis and abdominal free fluid in sonographic report. These findings suggested the diagnosis of acute appendicitis and the patient underwent appendectomy, after the operation, the platelet count became normal. The pathologic report of the specimen of the appendix was carcinoid tumor. Now the question is whether the appendiceal carcinoid tumor can be the reason of symptoms of chronic idiopathic.

  5. Chronic pediatric pulmonary disease and primary humoral antibody based immune disease.

    Science.gov (United States)

    Dosanjh, A

    2011-04-01

    Chronic inflammation of the larger airways is a common occurrence in children. A number of factors such as younger age, premature birth, male gender, exposure to environmental smoke or pollution, and crowded housing can increase a child's susceptibility to chronic lung disease. Chronic bronchitis may be caused by an underlying humoral immunodeficiency if the clinical course is recurrent or prolonged. Primary humoral immunodeficiency accounts for approximately 70% of all immunodeficiencies. The differential of chronic bronchitis also includes Cystic Fibrosis, ciliary defects and immune cellular and phagocytic defects. This review will summarize the most common humoral antibody based immune based deficiencies associated with chronic pulmonary disease.

  6. [State of local immunity in patients with chronic generalized parodontitis].

    Science.gov (United States)

    Schmidt, D V; Schmagel; Mozgovaia, L A; Beliaeva, O V

    2008-01-01

    The aim of this work was the determination of the state of local immunity in periodontal complex in patients with chronic generalized periodontitis (CGP). 96 individuals were examined (mean age 43.6+/-1.2 years). All the patients were divided into 2 groups: basic group with CGP patients (76 persons) and comparative group - individuals with intact periodontium (20 persons). To evaluate local immunity in dentogingival fluids the determination of concentrations of IgG, IgM, and IgA immunoglobulins has been used, as well as TNF-alpha, IL-1, IL-6, IL-8, INF-gamma, IL-1ra, IL-10, and IL-4 cytokines, and also factors controlling the state of bone tissue, namely, osteoprotegerine (OPG), and RANK-ligand. In gingival fluid of CGP patients the increase in both pro-, and anti-inflammatory mediators with indication to Th2-deviation (decrease of INF-gamma level and elevation of IL-4 level) was observed. CGP patients exhibited in their periodontal complex marked increase of IgG, IgM, and IgA concentrations that apparently evidenced to the consequence of local polyclonal activation of B-lymphocytes. Gingival fluid of CGP patients showed the elevation of RANKL, TNF-alpha, and IL-1 levels, and the decrease in OPG concentration that could be the reason for osteoclast activation and subsequent destruction of bone tissue. In case of CGP in the zone of periodontium developed inflammation that is characterized by elevated level of IL-8 and predominance of neutrophil number over the quantity of other types of leukocytes.

  7. Central immune alterations in passive strategy following chronic defeat stress.

    Science.gov (United States)

    Joana, Perez-Tejada; Amaia, Arregi; Arantza, Azpiroz; Garikoitz, Beitia; Eneritz, Gomez-Lazaro; Larraitz, Garmendia

    2016-02-01

    The relationship between stress, mood disorders and immune disorders is known, but what remains to be resolved is why certain individuals are more susceptible than others to suffer different disorders, along with the biological mechanisms that underlie these differences. The objective of this study was to analyze the changes in the expression patterns of proinflammatory cytokines in the hypothalamus, hippocampus, amygdala and prefrontal cortex after chronic defeat, depending on the coping strategy used. The expression levels of α1b and α2a adrenergic receptors and cytokine-inducible nitric oxide synthase (iNOS) in the prefrontal cortex were also measured. The results indicated that subjects with a passive coping strategy showed high levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression in several cerebral structures in resting conditions after 21 days of chronic stress and increases in these cytokine levels in the hippocampus following an additional stress. Low expression levels of tumour necrosis factor-alpha (TNF-α) in the prefrontal cortex in active subjects at rest and in passive subjects after an additional defeat were detected. The iNOS expression levels were lower in the prefrontal cortex of the active group at rest. With respect to adrenergic receptor expression, there were no changes as a function of stress, but there were changes as a function of coping strategy. These results indicate differences in the variables studied in terms of the coping strategy adopted, with passive subjects having a biological profile that could be considered more vulnerable to the development of stress-related disorders.

  8. CHRONIC URTICARIAL IN CHILDHOOD. IMMUNE PATHOLOGY OF CHRONIC URTICARIAL IN CHILDREN (PART I

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    N. A. Sinelnikova

    2013-01-01

    Full Text Available Abstract. This section of our review article deals with prevalence, genetic factors, and some immune mechanisms of chronic urticaria in children. In any form of chronic urticaria, the main pathogenetic role is ascribed to mast cells and basophiles. Increased production of cyto- and chemokines, e.g., CCL2, CХCL8, IL-1, IL-4, IL-6, IL-10, IL-13, IL-17, is observed during chronic inflammatory reactions typical to this disease. Activation of mast cells and basophiles proceeds via specific receptors on the target cell membranes. Autoimmune urticaria is of special importance. In this disorder, autoantibodies are directed against IgE or FCεRIα, thus causing histamine release, due to cross-linking of α-chains of high-affinity IgE receptor, or binding of IgE fixed on the mast cells. Degranulation of basophils is followed by occurrence of activation molecules (СD203с, CD63. Some workers presumet that association between СD203с expression and positive autologous serum skin test may be a sign of autoimmune process. Increased expression of CD40L ligand on the surface of activated T cells suggests enhanced signaling for B cell activation and production of autoantibodies.

  9. Cardiac surgery in a patient with immunological thrombocytopenic purpura: Complications and precautions

    Directory of Open Access Journals (Sweden)

    Vivek Chowdhry

    2013-01-01

    Full Text Available Immune thrombocytopenic purpura (ITP patients are at high-risk for bleeding complications during and after cardiac surgeries involving cardiopulmonary bypass. We report a patient with ITP with severe coronary artery disease and mitral valve regurgitation who underwent uncomplicated coronary artery bypass grafting and mitral valve replacement. Three weeks later, the patient was readmitted in a very low general condition with signs of pericardial tamponade. We describe our experience of managing the case.

  10. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Sk Md Fazle Akbar; Norio Horiike; Morikazu Onji

    2006-01-01

    Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses.However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult.During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective.A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

  11. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study

    DEFF Research Database (Denmark)

    Cheng, Gregory; Saleh, Mansoor N; Marcher, Claus

    2011-01-01

    Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period....

  12. Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    Nobuyuld Toshikuni; Ryumei Yamato; Haruhiko Kobashi; Ken Nishino; Nobu Inada; Ritsuko Sakanoue; Mitsuhiko Suehiro; Yoshinori Fujimura; Gotaro Yamada

    2008-01-01

    Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-yearold man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count.Interestingly, human leukocyte antigen genotyping detected the alleles DQBI*0601 and DRBI*0803, which are related to both PBC and ITP in Japanese patients.This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.

  13. Evaluation of chronic immune system stimulation models in growing pigs.

    Science.gov (United States)

    Rakhshandeh, A; de Lange, C F M

    2012-02-01

    Two experiments (EXPs) were conducted to evaluate models of immune system stimulation (ISS) that can be used in nutrient metabolism studies in growing pigs. In EXP I, the pig's immune response to three non-pathogenic immunogens was evaluated, whereas in EXP II the pig's more general response to one of the immunogens was contrasted with observations on non-ISS pigs. In EXP I, nine growing barrows were fitted with a jugular catheter, and after recovery assigned to one of three treatments. Three immunogens were tested during a 10-day ISS period: (i) repeated injection of increasing amounts of Escherichia coli lipopolysaccharide (LPS); (ii) repeated subcutaneous injection of turpentine (TURP); and (iii) feeding grains naturally contaminated with mycotoxins (MYCO). In EXP II, 36 growing barrows were injected repeatedly with either saline (n = 12) or increasing amounts of LPS (n = 24) for 7 days (initial dose 60 μg/kg body weight). Treating pigs with TURP and LPS reduced feed intake (P < 0.02), whereas feed intake was not reduced in pigs on MYCO. Average daily gain (ADG; kg/day) of pigs on LPS (0.50) was higher than that of pigs on TURP (0.19), but lower than that of pigs on MYCO (0.61; P < 0.01). Body temperature was elevated in pigs on LPS and TURP, by 0.8°C and 0.7°C, respectively, relative to pre-ISS challenge values (39.3°C; P < 0.02), but remained unchanged in pigs on MYCO. Plasma concentrations of interleukin-1β were increased in pigs treated with LPS and TURP (56% and 55%, respectively, relative to 22.3 pg/ml for pre-ISS; P < 0.01), but not in MYCO-treated pigs. Plasma cortisol concentrations remained unchanged for pigs on MYCO and TURP, but were reduced in LPS-treated pigs (30% relative to 29.8 ng/ml for pre-ISS; P < 0.05). Red blood cell glutathione concentrations were lower in TURP-treated pigs (13% relative to 1.38 μM for pre-ISS; P < 0.05), but were unaffected in pigs on LPS and MYCO. In EXP I, TURP caused severe responses including skin ulceration and

  14. Disruption of Immune Regulation by Microbial Pathogens and Resulting Chronic Inflammation

    OpenAIRE

    2013-01-01

    Activation of the immune response is a tightly regulated, coordinated effort that functions to control and eradicate exogenous microorganisms, while also responding to endogenous ligands. Determining the proper balance of inflammation is essential, as chronic inflammation leads to a wide array of host pathologies. Bacterial pathogens can instigate chronic inflammation via an extensive repertoire of evolved evasion strategies that perturb immune regulation. In this review, we discuss two model...

  15. Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

    Science.gov (United States)

    Gungor, Bilgi; Kahraman, Tamer; Gursel, Mayda; Yilmaz, Bilge

    2017-01-01

    Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. PMID:28170444

  16. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog...

  17. In vivo immunization in combination with peg-interferon for chronic hepatitis B virus infection

    NARCIS (Netherlands)

    Sprengers, D; van der Molen, R G; Binda, R; Kusters, J G; de Man, R A; Niesters, H G M; Schalm, S W; Janssen, H L A

    2007-01-01

    Only in a minority of patients with chronic hepatitis B (CHB) will treatment with interferon (IFN)-alpha or nucleoside analogues lead to sustained virological response. In vivo immunization (IVI) following virus suppression aims to optimize conditions for an effective immune response: following rapi

  18. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

    Science.gov (United States)

    Kim, Edy Y; Battaile, John T; Patel, Anand C; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H; Benoit, Loralyn A; Byers, Derek E; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W; Morton, Jeffrey D; Castro, Mario; Polineni, Deepika; Patterson, G Alexander; Schwendener, Reto A; Allard, John D; Peltz, Gary; Holtzman, Michael J

    2008-06-01

    To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

  19. Moxifloxacin (Avelox Induced Thrombotic Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Sikander P. Surana

    2012-01-01

    Full Text Available We report a case of a 66-year-old African-American female who presented with complaints of progressively worsening weakness, shortness of breath on minimal exertion, lethargy for the last few days, and short episodes of aphasia lasting 20–30 seconds. Prior to presentation, she was treated with two courses of moxifloxacin for sinusitis. Laboratory examination was remarkable for anemia and thrombocytopenia with elevated lactate dehydrogenase and no evidence of renal failure. Peripheral smear showed numerous schistocytes and she was diagnosed with thrombotic thrombocytopenic purpura. Moxifloxacin was identified as the offending agent. The patient was treated with prednisone and plasmapheresis. To the best of our knowledge, this is the first reported case of thrombotic thrombocytopenic purpura associated with the use of moxifloxacin. Although rare, physicians should be aware of this serious complication associated with its use.

  20. Thrombocytopenic purpura: Importance of early diagnosis

    OpenAIRE

    Linklater, David M.; Voth, Arnold

    1996-01-01

    Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are important diagnostic considerations for family physicians because therapy can be lifesaving. Treatment with plasmapheresis is usually successful. Therefore, early diagnosis is essential. A patient with microangiopathic hemolytic anemia is described. Diagnosis of Hodgkin's disease was confirmed after the initial episode. The case highlights the important role of family physicians in the diagnosis and treatment of uncommon he...

  1. Thrombotic Thrombocytopenic Purpura Associated with Pneumococcal Sepsis

    Directory of Open Access Journals (Sweden)

    Jeffrey R Schriber

    1993-01-01

    Full Text Available The first documented case of thrombotic thrombocytopenic purpura (TTP associated with pneumococcal septicemia is reported. This association has been previously demonstrated with hemolytic uremic syndrome. The patient presented with recurrent seizures, oliguric renal failure, fever, thrombocytopenia and microangiopathic hemolytic anemia; coagulation studies were normal. Blood and sputum cultures were positive for Streptococcus pneumoniae. The patient responded to therapy with plasmapheresis and antiplatelet agents as well as antibiotics. Coincident infection should be searched for in all cases of TTP.

  2. Natural Health Products, Modulation of Immune Function and Prevention of Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Pierre S. Haddad

    2005-01-01

    Full Text Available The immune system is increasingly found to be involved in the development of several chronic illnesses, for which allopathic medicine has provided limited tools for treatment and especially prevention. In that context, it appears worthwhile to target the immune system in order to modulate the risk of certain chronic illnesses. Meanwhile, natural health products (NHPs are generating renewed interest, particularly in the prevention and treatment of several chronic diseases. Over 20 scientists from fields related to immune function and NHPs were thus convened to establish the state of knowledge on these subjects and to explore future research directions. This review summarizes the result of discussions held during the symposium. It thus seeks to be thought provoking rather than to comprehensively cover such broad areas of research. Notably, a brief overview of the immune system is presented, including potentially useful targets and strategies to keep it in an equilibrated state, in order to prevent certain disorders. The pertinence and limitations of targeting the immune system to prevent chronic diseases is also discussed. The paper then discusses the usefulness and limitations of current experimental tools available to study the immune modulating effects of NHPs. Finally, a concise review of some of the most studied NHPs showing promising immunomodulatory activity is given, and avenues for future research are described.

  3. Preoperative embolization of the splenic artery in patients that underwent splenectomy for immune thrombocytopenic purpura Embolização pré-operatória da artéria esplênica em pacientes submetidos à esplenectomia por púrpura trombocitopênica immune

    Directory of Open Access Journals (Sweden)

    PlínioCarlos Baú

    2007-12-01

    Full Text Available Transfusion of platelets, red blood cells, or both is usually necessary immediately after splenic artery ligature in patients with immune thrombocytopenic purpura who undergo splenectomy. PURPOSE: To investigate whether preoperative embolization of the splenic artery reduced the need for transfusion of platelets, red blood cells, or both. METHODS: Twenty- seven consecutive patients that underwent splenectomy for purpura between October 1999 and March 2006 performed by the same surgical team were enrolled. The first 17 patients did not undergo embolization and were compared with the next 10 patients, who composed the embolization group. RESULTS: The platelet count in the embolization group rose from a mean 7000 u/µl before to 75000 u/µl after the procedure. There was no need for platelet or red blood cell transfusion in the embolization group; in the group without preoperative embolization, 11 patients (p=0.001 required platelet transfusion and 8 (p=0.01, red blood cell transfusion. CONCLUSION: Embolization of the splenic artery before splenectomy is a safe method to avoid blood transfusions in patients with ITP.A transfusão de plaquetas e ou hemácias geralmente é realizada em pacientes submetidos a esplenectomia por Purpura Trombocitopênia Imune (PTI. OBJETIVO: Investigar se a embolização pré-operatória da artéria esplênica é eficaz na redução da necessidade de transfusão de hemácias ou plaquetas. MÉTODOS: Vinte e sete pacientes foram submetidos a esplenectomia por PTI de Outubro de 1999 a Março de 2006 pela mesma equipe cirúrgica. Os primeiros 17 pacientes não foram submetidos a embolização e foram comparados com os outros 10 individuos nos quais a embolização foi realizada. RESULTADOS: A contagem de plaquetas no grupo em que a embolização foi realizada subiu de uma média de 7000u/µl antes do procedimento, para 75000 u/µl após. Não foi necessário transfundir plaquetas ou glóbulos vermelhos no grupo submetido a

  4. The effect of physician’s recommendation on seasonal influenza immunization in children with chronic diseases

    Directory of Open Access Journals (Sweden)

    Pandolfi Elisabetta

    2012-11-01

    Full Text Available Abstract Background Despite recommendations by Health Authorities, influenza immunization coverage remains low in children with chronic diseases. Different medical providers involved in the management of children with chronic conditions may affect the pattern of influenza vaccine recommendations and coverage. The likelihood of vaccination by type of provider in children with chronic conditions is poorly understood. Therefore, the objectives of this study were to analyze the pattern and the effect of recommendations for seasonal influenza immunization provided by different physician profiles to families of children with chronic diseases and to measure the frequency of immunization in the study population. Methods We recruited children with chronic diseases aged 6 months–18 years who subsequently presented to specialty clinics for routine follow-up visits, during spring 2009, in three Italian Regions Families of children with chronic diseases were interviewed during routine visits at reference centers through a face-to-face interview. We analyzed the following immunization predictors: having received a recommendation toward influenza immunization by a health provider; child’s sex and age; mothers and fathers’ age; parental education and employment; underlying child’s disease; number of contacts with health providers in the previous year. Influenza immunization coverage was calculated as the proportion of children who received at least one dose of seasonal influenza vaccine in the previous season. We calculated prevalence ratios and we used a generalized linear model with Poisson family, log link and robust error variance to assess the effect of socio-demographic variables, underlying diseases, and recommendations provided by physicians on influenza immunization. Results We enrolled 275 families of children with chronic diseases. Overall influenza coverage was 57.5%, with a low of 25% in children with neurological diseases and a high of 91

  5. The Jeremiah Metzger Lecture: Inflammation, Immune Modulators, and Chronic Disease.

    Science.gov (United States)

    Dubois, Raymond N

    2015-01-01

    Chronic inflammation is a risk factor for many different diseases. It is clear that inflammation is associated with degenerative brain diseases, obesity, metabolic syndrome, cardiovascular disease, diabetes, and cancer. Throughout the past 100 years, changes in the causes of death in the US have been dramatic. The most recent data indicate that cardiovascular disease and cancer are now responsible for 63% of mortality in the US population. Although progression of these diseases is related to diet, lifestyle, and genetic factors, a common but often unrecognized link is the presence of underlying chronic inflammation. As of 2014, 83.6 million people were living with some form of cardiovascular disease, 29.1 million people have been diagnosed with diabetes, 14 million people carried the diagnosis of cancer, and 5.2 million people were living with Alzheimer disease. These diseases are a huge burden on our health care system and all have been associated with chronic inflammation.

  6. The clinical significance of immune-related marker detection in idiopathic thrombocytopenic purpura%特发性血小板减少性紫癜患者免疫相关指标的检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    陈剑芳; 杨林花; 冯建军; 常丽贤; 刘秀娥; 鹿育晋

    2010-01-01

    Objective To assess the clinical significance of detecting the immune markers in idiopathic thrombocytopenic purpura (ITP). Methods The frequencies of circulating B cells secreting platelet-specific antibody, platelet-specific antibody, the percentage of T lymphocyte subsets, the percentage of reticulated platelet and the level of thrombopoietin in 64 ITP patients and 31 healthy controls were measured with enzyme-linked immunospot assay (ELISPOT),modified monoclonal antibody immunobilization of platelet antigens assay (MAIPA), flow cytometry and sandwich enzyme-linked innnunosorbent assay respectively. Results Compared with the controls[1.3 ± 0. 5/105 peripheral blood mononuclear cell (PBMC), (0.33±0.06,0.41±0.03), (22.08±4.54)% and (8.19±2.46)%], the frequencies of circulating B cells secreting platelet-specific antibody (7.6±4.6/105 PBMC in acute ITP group, 5.3±3.0/105 PBMC in chronic ITP group), platelet-specific antibody (including the anti-GP Ⅱ b/Ⅲa antibody, anti-GP Ⅰ b/X antibody) (0.51 ±0.11, 0.48±0.06 in acute ITP group; 0.49±0.10,0.46±0.09 in chronic ITP group), the percentage of CD8+ T Lymphocyte (27.09±9.86 ) %, the percentage of reticulated platelet in ITP patients[the megakaryocyte cytosis group (24. 85 ± 19. 18)%, the normal megakaryocyte group (23.89±18.90)%]were significantly increased ( all P<0.05).The frequencies of circulating B cells secreting platelet-specific antibody in acute ITP patients were notably increased (P<0.05) compared to the chronic ITP patients. In T lymphocyte subsets, the percentage of CD3+T lymphocyte and CD4+ T lymphocyte and the ratio of CD4+/CD8+ in the patients with ITP[(60.88±14.59)%, (28.41±10.55)%, 1.18±0.59]were notably decreased than those in the healthy controls [(69.89±6.43)%, (35.38±5.05) %, 1.64±0.29, P<0.05]. There was no apparent difference of the level of thrombopoietin between ITP patients with megakaryocyte cytosis (72. 09 ± 41.64 ) and health controls (75.37± 26. 32, P > 0

  7. EB病毒感染与儿童急性免疫性血小板减少性紫癜关系的初步探讨%Preliminary Exploration of the Relationship between Epstein-Barr Virus Infection and Acute Immune Thrombocytopenic Purpura in Children

    Institute of Scientific and Technical Information of China (English)

    颜慕霞; 张力; 林涛

    2011-01-01

    目的 探讨Epstein-Barr病毒(EBV)感染与儿童急性免疫性血小板减少性紫癜(ITP)的关系.方法 分别用实时荧光定量聚合酶链反应(FQ-PCR)方法和血清酶联免疫吸附试验(ELISA)方法检测115例急性ITP患儿和50例健康儿童的EBV DNA和EBV IgM抗体.结果 急性ITP患儿EBV DNA、EBV IgM阳性率均明显高于健康对照儿童,差异均有统计学意义(P<0.01).结论 儿童感染EB病毒可能是儿童发生急性免疫性血小板减少性紫癜的重要因素之一.%Objective To explore the relationship between Epstein-Barr Virus ( EBV ) infection and acute immune thrombocytopenic purpura ( aITP ) in children.Methods EBV-DNA in peripheral blood and serum EBV-IgM in 115 cases with ITP and 50 healthy children were detected by fluorescence quantitative-polymerase chain reaction( FQ-PCR ) and enzyme linked immunosorbent assay( ELISA ).Results The positive rates of EBV DNA,EBV IgM in the aITP group were higher than in the control group.There were significant difference between the two groups( P < 0.01 ).Conclusion EBV infection may be an important pathogenic factor of aITP in children.

  8. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

    Directory of Open Access Journals (Sweden)

    Avital F. Barak

    2011-12-01

    Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

  9. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...... of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  10. Impaired SNX9 Expression in Immune Cells during Chronic Inflammation: Prognostic and Diagnostic Implications.

    Science.gov (United States)

    Ish-Shalom, Eliran; Meirow, Yaron; Sade-Feldman, Moshe; Kanterman, Julia; Wang, Lynn; Mizrahi, Olga; Klieger, Yair; Baniyash, Michal

    2016-01-01

    Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition. We found that myeloid-derived suppressor cells, which are elevated in the course of chronic inflammation, are responsible for the observed SNX9 reduced expression. Moreover, SNX9 downregulation is reversible, as its expression levels return to normal and immune functions are restored when the inflammatory response and/or myeloid-derived suppressor cells are neutralized. SNX9 downregulation was detected in numerous mouse models for pathologies characterized by chronic inflammation such as chronic infection (Leishmania donovani), cancer (melanoma and colorectal carcinoma), and an autoimmune disease (rheumatoid arthritis). Interestingly, reduced levels of SNX9 were also observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host's immune status and inflammatory stage. Our new discovery of SNX9 as being regulated by chronic inflammation and its association with immunosuppression, in addition to the CD247 regulation under such conditions, show the global impact of chronic inflammation and the generated immune environment on different cellular pathways in a diverse spectrum of diseases.

  11. STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.

    Science.gov (United States)

    Desvignes, Ludovic; Weidinger, Carl; Shaw, Patrick; Vaeth, Martin; Ribierre, Theo; Liu, Menghan; Fergus, Tawania; Kozhaya, Lina; McVoy, Lauren; Unutmaz, Derya; Ernst, Joel D; Feske, Stefan

    2015-06-01

    Chronic infections induce a complex immune response that controls pathogen replication, but also causes pathology due to sustained inflammation. Ca2+ influx mediates T cell function and immunity to infection, and patients with inherited mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we demonstrate that STIM1 is required for T cell-mediated immune regulation during chronic Mtb infection. Compared with WT animals, mice with T cell-specific Stim1 deletion died prematurely during the chronic phase of infection and had increased bacterial burdens and severe pulmonary inflammation, with increased myeloid and lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly reduced IFN-γ production during the early phase of Mtb infection, bacterial growth was not immediately exacerbated. During the chronic phase, however, STIM1-deficient T cells displayed enhanced IFN-γ production in response to elevated levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with impaired activation-induced cell death upon repeated TCR engagement and pulmonary lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb-infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells (iTregs) due to a T cell-intrinsic requirement for STIM1 in iTreg differentiation and excessive production of IFN-γ and IL-12, which suppress iTreg differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell-mediated immune regulation to limit injurious inflammation during chronic infection.

  12. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases.

    Science.gov (United States)

    Khatami, Mahin

    2009-01-01

    Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

  13. Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

    DEFF Research Database (Denmark)

    Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

    2016-01-01

    that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection. The aim of this study was to describe immune recovery in primary and chronic HIV infection and possible impact of TSLP. METHODS...

  14. SOME FEATURES OF IMMUNE STATUS IN THE CHILDREN WITH CHRONIC TONSILLITIS

    Directory of Open Access Journals (Sweden)

    O. V. Sorokin

    2007-01-01

    Full Text Available Abstract. The article provides some characteristics of immune status in the children suffering from chronic tonsillitis. Gender-associated peculiarities are taken into account, and comparative efficiency of certain rehabilitative therapeutic approaches is demonstrated for the children with different recurrence rates of this disorder.

  15. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    Science.gov (United States)

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  16. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ke-Xia Wang; Li-Hua Zhang; Jiang-Long Peng; Yong Liang; Xue-Feng Wang; Hui Zhi; Xiang-Xia Wang; Huan-Xiong Geng

    2005-01-01

    AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.METHODS: The levels of T lymphocyte subsets and mlL-2R in peripheral blood mononuclear cells (PBMCs)were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole.RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole.CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

  17. Systemic lupus erythematosus and thrombotic thrombocytopenic purpura:report of three cases

    Institute of Scientific and Technical Information of China (English)

    张文; 尤欣; 董怡

    2004-01-01

    @@ Systemic lupus erythematosus (SLE) is a multisystemic disease characterized by an autoimmune reaction.Thrombotic thrombocytopenic purpura (TTP) is a rare but severe syndrome with the manifestations of fever,thrombocytopenia, microangiopathic hemolysis,neurological symptoms, and renal involvement. The initial prognosis was reported to be dismal, 90% of patients dying within 3 months of onset. However, with the possibility of combined treatments, the survival rate has considerably improved. Data suggest a possible role of immune mechanisms in the development of TTP. 1,2We here report three cases of SLE complicated with TTP,and review the diagnosis, treatment, and outcome of SLE with TTP.

  18. Thrombotic thrombocytopenic purpura concomitant with autoimmune thyroiditis

    Directory of Open Access Journals (Sweden)

    Ali Bay

    2011-12-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is characterized by disseminated thrombotic occlusions located in the microcirculation, microangiopathic hemolytic anemia, thrombocytopenia, fever, and renal and neurologic abnormalities. A 14 year old girl admitted to our hospital complaining bruising on her body and prolonged menstrual bleeding. On her physical examination there were very common bruising on four extremities. On the laboratory studies, Hemoglobin was 9 g/dL; Hematocrit, 24%; white blood count 11600/mm3 and thrombocyte count, 9.000/mm3. According to these findings our first diagnose was idiopatic thrombocytopenic purpura so intravenous immunoglobulin was given to patient for two days. Bone marrow aspiration was performed because of persisting thrombocytopenia despite two days IVIG therapy. Increased number of megakaryocytes was seen in bone marrow. Some accompanying symptoms like headache, numbness in per oral region and extremities, difficulty in speaking, and fluctuation in consciousness for short time occurred. The patient was reevaluated; because thrombocytopenia persisted and some neurological symptoms was observed. Due to these findings we thought that TTP was the diagnosed and plasma exchange was started. Increase was seen in platelet count in the second days of treatment. TTP should be considered in children presenting with atypical thrombocytopenia.

  19. Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

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    Christopher Coleman

    2014-01-01

    Full Text Available Pulmonary hyalinizing granuloma (PHG is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP in our patient, may also favor HG. In this case report we find an association between PHG and ITP.

  20. Immunization coverage and timeliness of vaccination in Italian children with chronic diseases.

    Science.gov (United States)

    Pandolfi, E; Carloni, E; Marino, M G; Ciofi degli Atti, M L; Gesualdo, F; Romano, M; Giannattasio, A; Guarino, A; Carloni, R; Borgia, P; Volpe, E; Perrelli, F; Pizzuti, R; Tozzi, A E

    2012-07-20

    Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months-18 years were included in the study. Coverage for diphtheria-tetanus-pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles-mumps-rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.

  1. 白介素-11联合激素治疗慢性特发性血小板减少性紫癜的起效时间及血小板变化情况研究%STUDY OF THE ONSET TIME AND THE CHANGE IN TREATMENT FOR CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA WITH INTERLEUKIN -11 AND HORMONE

    Institute of Scientific and Technical Information of China (English)

    郑冬丽

    2011-01-01

    [Objective]To investigate the onset time and platelet changes in the treatment of chronic idiopathic thrombo-cytopenic purpura with IL -11 combined with dexamethasone.[Methods]90 chronic idiopathic thrombocytopenic puipura patients as research subjects in our hospital from January 2006-January 2010 were randomly divided into three groups, of which A group carried out IL -11 treatment, B group treated with dexamethasone, C group were combined hormone Interleukin -11 treated, observed and compared the onset time and platelet changes in three groups.[Results]After treatment, the total effective rate in C group was significantly higher than that in group A, B, and the time that C group reached the normal level of platelets was significantly shorter with the A group, B group (P all < 0.05).After beingtreated, platelets were significantly higher in three groups than before treatment, C group with more obvious increase, showed statistically significant differences between groups (P all < 0.05).The side effects were insomnia, hypertension, hyperglycemia, secondary infection, moon face, central obesity, and gastrointestinal bleeding.The incidence of side effects in C group was significantly lower than A, B groups, it showed statistically significant difference (P both <0.05), but between A, B groups, it showed no significance (P > 0.05).[Conclusion]Interleukin -11 combined hormone treatment for chronic idiopathic thrombocytopenic purpura is with faster onset time and less side reactions, significantly improves platelet function, which is worthy of clinical application.%[目的]探讨白介素-11联合地塞米松治疗慢性特发性血小板减少性紫癜的起效时间及血小板变化情况.[方法]选取某院2006年1月~2010年1月住院治疗的90例慢性特发性血小板减少性紫癜患者作为研究对象,随机分为3组各30例,其中A组采用白介素-11进行治疗,B组采用地塞米松进行治疗,C组采用白介素-11联合

  2. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    Michelle Fog Andersen

    2015-01-01

    Full Text Available Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting.

  3. Púrpura trombocitopênica imunológica como manifestação inicial de lúpus eritematoso sistêmico juvenil Idiopathic thrombocytopenic purpura as initial manifestation of juvenile systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Josefina Aparecida Pellegrini Braga

    2003-12-01

    salientar a importância da determinação de auto-anticorpos para lúpus eritematoso sistêmico nas crianças com a forma crônica desta patologia.Patients with Idiopathic Thrombocytopenic Purpura (ITP present a high trend to develop Systemic Lupus Erythematosus (SLE, especially those with chronic presentation. Some authors observed that female gender, older patients and familial history of autoimmune disease in patients with Idiopathic Thrombocytopenic Purpura are factors that lead to increased susceptibility for the development of Systemic Lupus Erythematosus. Based on these facts, we decided to study 5 children with chronic Idiopathic Thrombocytopenic Purpura and late Systemic Lupus Erythematosus. In this paper, we describe the clinical and laboratorial features of 5 female children with Idiopathic Thrombocytopenic Purpura that later developed Systemic Lupus Erythematosus. All patients were girls, 3 Caucasian, with Idiopathic Thrombocytopenic Purpura onset age ranged between 6 years and 3 months and 12 years and 1 month (mean - 9 years and 2 months. The age at Systemic Lupus Erythematosus diagnosis ranged between 8 years and 13 years and 8 months (mean - 10 years and 10 months. Though, the gap between Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus diagnosis ranged between 11 months and 2 years and 9 months (mean - 1 year and 10 months. All patients presented chronic Idiopathic Thrombocytopenic Purpura (thrombocytopenia lasts longer than 6 months. The Systemic Lupus Erythematosus classification criteria were (in decreasing frequency: malar erythema and positivity of ANA in 5 patients; arthritis, hematological (thrombocytopenia and immunological alterations (positivity of anti-DNA in 4 patients; photosensitivity and positivity of anti-cardiolipin in 3 patients. Other manifestations included oral ulcers, renal involvement, leukopenia and auto-immune hemolytic anemia, serositis (pericarditis, neurological involvement and positivity of anti-Sm antibody

  4. Decreased peripheral natural killer cells activity in the immune activated stage of chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available BACKGROUND & AIMS: The natural course of chronic hepatitis B virus (HBV infection is characterized by different immune responses, ranging from immune tolerant (IT to immune activated (IA stages. In our study, we investigated the natural killer (NK cells activity in patients at different immunological stages of chronic HBV infection. METHODS: Blood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB, including 15 patients in the immune tolerant (IT stage, 42 patients in the immune activated (IA stage, and 18 healthy individuals (HI. The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity. RESULTS: NK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (p<0.05. Patients in the IA stage of CHB had lower levels of NK cells activating receptor NKp30 and NKG2D expression, cytokine interferon-γ (IFN-γ and tumor necrosis factor-α (TNF-α production, as compared to patients in the IT stage and HI, respectively (p<0.05. Cytotoxicity of NK cells was lower in patients in the IA stage of CHB compared to patients in the IT stage and HI, respectively (p<0.05. The level of IFN-γ but not level of TNF-α and cytotoxicity of NK cells was inversely correlated with serum HBV load in patients with CHB. Peripheral NK cells activity did not correlate with ALT level. CONCLUSION: NK cells activity was lower in CHB patients, especially in those in the IA stage.

  5. Health related quality of life of chronic patients with immune system diseases: a pilot study

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    Claudia Campos Ribeiro

    2012-06-01

    Full Text Available Health related quality of life (HRQL and survival are two important outcome measures in chronic diseases. This study aimed to compared HRQL in patients with different chronic diseases of immune system and normative data from the general Portuguese Population. It was selected 103 out-patients, by convenience, to complete SF-36v2. The lowest scores were found among measures for general health (41.0, vitality (47.5, bodily pain (51.0, mental health (56.4; women, except for role-physical, and patients with auto-immune diseases have had the worse scores on all assessed dimension of subjective health, when compared with normative data. Highest scores were obtained in the following scales: physical functioning (69.1, social functioning (66.9, role-emotional (64.9. Living with chronic immune disease have impact on HRQL and it can be expected that the Portuguese version of SF-36v2 provide valid and reliable HRQL data.

  6. AGEs and chronic subclinical inflammation in diabetes: disorders of immune system.

    Science.gov (United States)

    Hu, Hang; Jiang, Hongfei; Ren, Haitao; Hu, Xinlei; Wang, Xingang; Han, Chunmao

    2015-02-01

    Chronic subclinical inflammation represents a risk factor of type 2 diabetes and several diabetes complications, including neuropathy and atherosclerosis including macro-vasculopathy and micro-vasculopathy. However, the inflammatory response in the diabetic wound was shown to be remarkably hypocellular, unregulated and ineffective. Advanced glycation end products (AGEs) and one of its receptors, RAGE, were involved in inducing chronic immune imbalance in diabetic patients. Such interactions attracts immune cell into diffused glycated tissue and activates these cells to induce inflammatory damage, but disturbs the normal immune rhythm in diabetic wound. Traditional measurements of AGEs are high-performance liquid chromatography and immunohistochemistry staining, but their application faces the limitations including complexity, cost and lack of reproducibility. A new noninvasive method emerged in 2004, using skin autofluorescence as indicator for AGEs accumulation. It had been reported to be informative in evaluating the chronic risk of diabetic patients. Studies have indicated therapeutic potentials of anti-AGE recipes. These recipes can reduce AGE absorption/de novo formation, block AGE-RAGE interaction and arrest downstream signaling after RAGE activation.

  7. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    Science.gov (United States)

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  8. Chronic Schistosoma japonicum infection reduces immune response to vaccine against hepatitis B in mice.

    Directory of Open Access Journals (Sweden)

    Lin Chen

    Full Text Available BACKGROUND: Hepatitis B and schistosomiasis are most prevalent in Africa and Asia, and co-infections of both are frequent in these areas. The immunomodulation reported to be induced by schistosome infections might restrict immune control of hepatitis B virus (HBV leading to more severe viral infection. Vaccination is the most effective measure to control and prevent HBV infection, but there is evidence for a reduced immune response to the vaccine in patients with chronic schistosomiasis japonica. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate in a mouse model that a chronic Schistosoma japonicum infection can inhibit the immune response to hepatitis B vaccine (HBV vaccine and lead to lower production of anti-HBs antibodies, interferon-γ (IFN-γ and interleukin-2 (IL-2. After deworming with Praziquantel (PZQ, the level of anti-HBs antibodies gradually increased and the Th2-biased profile slowly tapered. At 16 weeks after deworming, the levels of anti-HBs antibodies and Th1/Th2 cytokines returned to the normal levels. CONCLUSIONS/SIGNIFICANCE: The results suggest that the preexisting Th2-dominated immune profile in the host infected with the parasite may down-regulate levels of anti-HBs antibodies and Th1 cytokines. To improve the efficacy of HBV vaccination in schistosome infected humans it may be valuable to treat them with praziquantel (PZQ some time prior to HBV vaccination.

  9. Influence on the mouse immune system of chronic ingestion of {sup 137}Cs

    Energy Technology Data Exchange (ETDEWEB)

    Bertho, Jean-Marc; Faure, Marie-Cecile; Louiba, Sonia; Tourlonias, Elie; Stefani, Johanna; Siffert, Baptiste; Paquet, Francois; Dublineau, Isabelle, E-mail: Jean-marc.bertho@irsn.fr [IRSN, Laboratoire de Radiotoxicologie Experimentale, Fontenay aux Roses (France)

    2011-03-01

    The aim of this work was to determine the possible occurrence of damage to the immune system during the course of chronic ingestion of {sup 137}Cs. BALB/C mice were used, with {sup 137}Cs intake via drinking water at a concentration of 20 kBq l{sup -1}. Adults received {sup 137}Cs before mating and offspring were sacrificed at various ages between birth and 20 weeks. Phenotypic analysis of circulating blood cells and thymocytes did not show any significant modification of immune cell populations in animals ingesting {sup 137}Cs as compared with control animals, with the exception of a slight increase in Treg percentage at the age of 12 weeks. Functional tests, including proliferative response to mitogens such as phytohaemagglutinin, response to alloantigens in mixed lymphocyte reaction and immunoglobulin response to vaccine antigens such as tetanus toxin and keyhole limpet haemocyanin did not show any significant functional modification of the immune system in {sup 137}Cs-ingesting animals as compared with control animals. Overall, our results suggest that chronic ingestion of a low concentration of {sup 137}Cs in drinking water in the long term does not have any biologically relevant effect on the immune system.

  10. Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

    Science.gov (United States)

    Synhaeve, Nicholas; Musilli, Stefania; Stefani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc

    2016-03-01

    Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of (90)Sr ingestion on the immune system, the animals were chronically exposed to (90)Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19(+) B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which (90)Sr acts on the immune system remain to be elucidated. However, our results suggest that (90)Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout.

  11. Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders

    Science.gov (United States)

    te Velde, Anje A.; Bezema, Tjitske; van Kampen, Antoine H. C.; Kraneveld, Aletta D.; 't Hart, Bert A.; van Middendorp, Henriët; Hack, Erik C.; van Montfrans, Joris M.; Belzer, Clara; Jans-Beken, Lilian; Pieters, Raymond H.; Knipping, Karen; Huber, Machteld; Boots, Annemieke M. H.; Garssen, Johan; Radstake, Tim R.; Evers, Andrea W. M.; Prakken, Berent J.; Joosten, Irma

    2016-01-01

    In order to combat chronic immune disorders (CIDs), it is an absolute necessity to understand the bigger picture, one that goes beyond insights at a one-disease, molecular, cellular, and static level. To unravel this bigger picture we advocate an integral, cross-disciplinary approach capable of embracing the complexity of the field. This paper discusses the current knowledge on common pathways in CIDs including general psychosocial and lifestyle factors associated with immune functioning. We demonstrate the lack of more in-depth psychosocial and lifestyle factors in current research cohorts and most importantly the need for an all-encompassing analysis of these factors. The second part of the paper discusses the challenges of understanding immune system dynamics and effectively integrating all key perspectives on immune functioning, including the patient’s perspective itself. This paper suggests the use of techniques from complex systems science in describing and simulating healthy or deviating behavior of the immune system in its biopsychosocial surroundings. The patient’s perspective data are suggested to be generated by using specific narrative techniques. We conclude that to gain more insight into the behavior of the whole system and to acquire new ways of combatting CIDs, we need to construct and apply new techniques in the field of computational and complexity science, to an even wider variety of dynamic data than used in today’s systems medicine. PMID:28018353

  12. Engagement of specific innate immune signaling pathways during Porphyromonas gingivalis induced chronic inflammation and atherosclerosis.

    Science.gov (United States)

    Gibson, Frank C; Ukai, Takashi; Genco, Caroline A

    2008-01-01

    Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. The expression of TLRs are markedly augmented in human atherosclerotic lesions and this occurs preferentially by endothelial cells and macrophages in areas infiltrated with inflammatory cells. Furthermore polymorphisms in the human gene encoding one TLR receptor (TLR4) which attenuates receptor signaling and diminishes the inflammatory response to gram-negative pathogens, is associated with low levels of certain circulating mediators of inflammation and a decreased risk for atherosclerosis in humans. Recent advances have established a fundamental role for inflammation in mediating all stages of atherosclerosis. However, the triggers that initiate and sustain the inflammatory process have not been definitively identified. Although definitive proof of a role of infection contributing to atherogenesis is lacking, multiple investigations have demonstrated that infectious agents evoke cellular and molecular changes supportive of such a role. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen Porphyromonas gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. We have also established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate

  13. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  14. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    Energy Technology Data Exchange (ETDEWEB)

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  15. Clinical use of enteral immune nutrition in patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Zhi-cheng ZHANG

    2015-06-01

    Full Text Available Objective To investigate the use of enteral immune nutrition preparation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD, regard its efficacy in improving nutritional status, and its influence on immunity and the status of acute inflammatory reaction of the patients. Methods Sixty-two AECOPD patients requiring mechanical ventilation in ICU of our hospital were randomly divided into two groups: immune nutrition group [study group, n=32, receiving Ruineng (a product of Huarui Pharmaceutical Ltd., which contained essential fatty acids, Omega-3 fatty acids, and energy 1.3 kcal/ml] and conventional nutrition group (control group, n=30, receiving the hospital self-made homogenized diet with 1.2 kal/ml. Patients in the two groups took enteral nutrition of equal calorie, and it was given by nasointestinal tube. On the day of admission and the 14th and 18th after admission, venous blood was obtained for the determination of serum albumin, prealbumin, transferrin, C reactive protein (CRP, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6. At the same time upper arm muscle circumference (MAMC was measured at the bed side. The 14-day off-respirator rate and mechanical ventilation time within 28 days were compared between the two groups. Results The 14-day off-respirator rate was higher in study group than in control group (P0.05. Conclusions Compared with homogenized diet, immune enteral nutrition could better improve the nutritional status and immune function, lower the acute inflammatory response level, increase the success rate of early off-respirator in AECOPD patients, therefore, enteral immune nutrition preparation is a better nutrition support solution for AECOPD. DOI: 10.11855/j.issn.0577-7402.2015.05.17

  16. [Thrombotic thrombocytopenic purpura disclosing cancer: apropos of 2 cases].

    Science.gov (United States)

    Girard, P; Tardy, B; Page, Y; Mosnier, J F; Tardy-Poncet, B; Bertrand, J C

    1995-01-21

    Thrombotic thrombocytopenic purpura (TTP) causes severe haemolytic anaemia, thrombopenia, fever and neurological and renal involvement. Currently five large aetiologic groups have been identified: viral or bacterial infection, drugs, conjunctive tissue diseases, pregnancy and solid tumours. We observed two cases resulting from an adenocarcinoma. In the first case, a 71-year-old man with chronic silicosis, the presenting signs were asthenia, fever, epistaxis with diffus purpura and spontaneous haematomas of the lower limbs. Diagnosis of TTP was based on routine laboratory tests and the patient responded well to fresh frozen plasma. On the 5th day of treatment, haemoglobin level dropped sharply and melana occurred. Upper digestive tract endoscopy revealed a tumoural formation of the antrum-fundic junction and histology examination of the biopsy confirmed the diagnosis of adenocarcinoma. Ten months after gastrectomy the patient was in excellent health with no relapse of the TTP. In the second case, the presenting signs included spontaneous haematomas, rectorrhagia and low grade fever. Microscopic haematuria and renal failure were observed in addition to the biological syndrome of TTP. The patient responded poorly to fresh frozen plasma and packed cell transfusions. Plasma exchange was equally unsuccessful. The disease continued a fulminant course and the diagnosis of adenocarcinoma located in a pulmonary lymph nodes was made at autopsy. These rare cases of TTP caused by cancer emphasize the importance of a thorough aetiological research. Plasma exchange has been shown to be effective but mortality at 1 year approximately 85% in cancer related cases. Early diagnosis and specific anti-cancer therapy might improve prognosis. We report our personal experience with 16 other similar cases.

  17. Ascorbic acid: its role in immune system and chronic inflammation diseases.

    Science.gov (United States)

    Sorice, Angela; Guerriero, Eliana; Capone, Francesca; Colonna, Giovanni; Castello, Giuseppe; Costantini, Susan

    2014-05-01

    Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs.

  18. Chronic Activation of Innate Immunity Correlates With Poor Prognosis in Cancer Patients Treated With Oncolytic Adenovirus.

    Science.gov (United States)

    Taipale, Kristian; Liikanen, Ilkka; Juhila, Juuso; Turkki, Riku; Tähtinen, Siri; Kankainen, Matti; Vassilev, Lotta; Ristimäki, Ari; Koski, Anniina; Kanerva, Anna; Diaconu, Iulia; Cerullo, Vincenzo; Vähä-Koskela, Markus; Oksanen, Minna; Linder, Nina; Joensuu, Timo; Lundin, Johan; Hemminki, Akseli

    2016-02-01

    Despite many clinical trials conducted with oncolytic viruses, the exact tumor-level mechanisms affecting therapeutic efficacy have not been established. Currently there are no biomarkers available that would predict the clinical outcome to any oncolytic virus. To assess the baseline immunological phenotype and find potential prognostic biomarkers, we monitored mRNA expression levels in 31 tumor biopsy or fluid samples from 27 patients treated with oncolytic adenovirus. Additionally, protein expression was studied from 19 biopsies using immunohistochemical staining. We found highly significant changes in several signaling pathways and genes associated with immune responses, such as B-cell receptor signaling (P immunity before treatment is associated with inferior survival in patients treated with oncolytic adenovirus. Conversely, lack of chronic innate inflammation at baseline may predict improved treatment outcome, as suggested by good overall prognosis.

  19. Immune activation response in chronic HIV-infected patients: influence of Hepatitis C virus coinfection.

    Directory of Open Access Journals (Sweden)

    Mercedes Márquez

    Full Text Available We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated.Seventy HIV-infected patients [monoinfected by HIV (n = 20, HCV-coinfected (with (n = 25 and without (n = 25 liver cirrhosis] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months.Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase.In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.

  20. Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

    Science.gov (United States)

    Márquez, Mercedes; Romero-Cores, Paula; Montes-Oca, Monserrat; Martín-Aspas, Andrés; Soto-Cárdenas, María-José; Guerrero, Francisca; Fernández-Gutiérrez, Clotilde; Girón-González, José-Antonio

    2015-01-01

    Objectives We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated. Patients and methods Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months). Results Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase. Conclusion In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients. PMID:25775475

  1. Supraclavicular lymph node tuberculosis presenting with immune thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    LU Hua; WANG Yong-ren; JI Ou; XU Wei; ZHANG Jian-fu; FAN Qin-he; LI Jian-yong

    2007-01-01

    @@ Tuberculosis (TB) differs from many other infectious maladies in having particular social and geographic distributions. The disease was under control in developed nations and being brought under control in developing countries, as in China.

  2. [Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura].

    Science.gov (United States)

    Sagawa, Morihiko; Takao, Masaki; Nogawa, Shigeru; Mizuno, Masafumi; Murata, Mitsuru; Amano, Takahiro; Koto, Atsuo

    2003-10-01

    In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.

  3. Expression of Transforming Growth Factor-β1 and Its Receptors in Peripheral Blood of Patients with Immune Thrombocytopenic Purpura%转化生长因子-β1及其受体在免疫性血小板减少性紫癜症患者中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    方治; 张翼鷟; 蔡挺; 李克强; 余静; 罗央清; 赵海丰

    2012-01-01

    本研究通过检测外周血转化生长因子( TGF-β1)及其受体((TGF-βR)的表达探讨其在免疫性血小板减少性紫癜症(ITP)发病中的作用机制.以ITP患者为研究对象,健康人为对照,通过实时PCR方法检测外周血中TGF-β1及其受体(TGF-βRⅠ、TGF-βRⅡ和TGF-βRⅢ)的表达量,分析两组之间的差异.结果表明,ITP患者组TGF-β1和TGF-βRⅡmRNA的表达明显高于正常对照组,差异有统计学意义,而TGF-βR Ⅰ mRNA的表达明显低于正常对照组,差异有统计学意义.TGF-βRⅢmRNA的表达在两组间无统计学差异.结论:TGF-β1及其受体TGF-βR Ⅰ和TGF-pRⅡ在ITP患者中表达异常,表明TGF-β1信号通路在ITP患者发病中可能具有一定的作用.%This study was purposed to detect the expression of transforming growth factor β1 (TGF-β1 ) and its receptors (TGF-pR) and to investigate their roles in pathogenesis of immune thrombocytopenic purpura (ITP). The expressions of TGF-β1 and their receptors TGF-βR I , TGF-pR H and TGF-pR i in the peripheral blood of patients with FTP and healthy persons were detected by the real-time PCR, and differences of their expression levels were analysed. The results showed that the expression of TGF-&1 and TGF-βR II mRNA in ITP patients was significantly higher than that in the healthy controls, while the TGF-pR I mRNA expression in ITP patient was significantly lower than that in the controls. The expression of TGF-βR HI was not statistically different between the two groups. It is concluded that TGF-βl and its receptors including TGF-pR I and TGF-βR II express abnormally in the peripheral blood of ITP patients, which suggests that the TGF-p signaling pathway probably play a vital role in the pathogenesis of the ITP.

  4. 地塞米松冲击疗法治疗成人原发免疫性血小板减少症的疗效观察%The Efficacy Observation of Dexamethasone Impact Therapy in the Treatment of Immune Thrombocytopenic Purpura

    Institute of Scientific and Technical Information of China (English)

    张付华; 刘珍

    2014-01-01

    目的:观察地塞米松冲击疗法治疗成人原发免疫性血小板减少症(ITP)的临床疗效。方法:自2006年7月-2013年9月间笔者所在医院收治成人ITP患者38例,患者均给予胸腺肽α1联合大剂量维生素C治疗,其中19例同时应用4 d地塞米松冲击治疗,观察临床症状、血小板计数和不良反应。结果:胸腺肽α1+大剂量维生素C治疗组总有效率78.9%,平均起效时间(16.8±3.2)d;胸腺肽α1+大剂量维生素C联合地塞米松冲击治疗组总有效率84.2%,平均起效时间(6.7±2.7)d。两种治疗方案的不良反应均较轻微。结论:胸腺肽α1联合大剂量维生素C与冲击量地塞米松联合应用治疗成人ITP疗效较好,副作用少,可缩短起效时间。%Objective:To observe the curative effect of Dexamethasone impact therapy to the immune thrombocytopenic purpura(ITP).Method:38 ITP patients were all given thymosin alpha 1(Tα1)combined high-dose vitamin C,among them 19 patients were companied with flushing dose dexamethasone during the first 4 medicative days.The clinic syndrome,platelet counts and side effects were observed.Result:The total effective rate in Tα1 combined high-dose vitamin C therapy group reached 78.9%,the average onset time were(16.8±3.2)d;the total effective rate in Tα1 combined high-dose vitamin C and flushing dose dexamethasone therapy group was 84.2%,the average onset time were(6.7±2.7)d.The side effects of the two groups were slight.Conclusion:Tα1 combined high-dose vitamin C and flushing dose dexamethasone has good curative effect and fewer side effects on adult ITP;it can also act fsatly.

  5. PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    M. V. Osikov

    2016-01-01

    Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

  6. Refractory thrombotic thrombocytopenic purpura following acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ebisa Bekele; Bethel Shiferaw; Alexandra Sokolova; Arpan Shah; Phillip Saunders; Alida Podrumar; Javed Iqbal

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder with an estimated incidence of 4–5 cases per million people per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia and organ damage. There are reports in literature that TTP and acute pancreatitis are associated, indicating each can be the cause of the other. However, acute pancreatitis triggering TTP is very rare. A 71 years old female presented with abdominal pain of 3 days, followed by dark urine. She had icteric sclera, petechial rash and mild epigastric tenderness. Lab findings were significant for hemolytic anemia, thrombocytopenia and elevated lipase. CT of abdomen showed evidence of pancreatitis and cholelithiasis. After admission, patient developed symptoms of stroke. Further investigation showed elevated lactate dehydrogenase and normal coagulation studied with peripheral blood smear showed 5–6 schistocytes/high power field. Disintegrin and metalloproteinase with thrombospondin motifs-13 (ADAMTS13) activity showed less than 3% with high ADAMTS13 inhibitor 2.2. Patient required 6–7 weeks of daily plasmapheresis until she showed complete response. Our patient presented with clinical features of pancreatitis prior to having dark urine and petechial rash. Therefore, we strongly believe that our patient had pancreatitis which was followed by TTP. Patient's ADMTS13 activity was 6%after 10 plasma exchanges, signifying refractory TTP and higher risk for morbidity and mortality. There are limited data and consensus on the management of refractory TTP. TTP and acute pancreatitis are associated. However, refractory TTP following acute pancreatitis is rarely mentioned in the literature. We would like to emphasize the importance of having higher clinical suspicion of the association of both disease entities.

  7. Possible lower rate of chronic ITP after IVIG for acute childhood ITP an analysis from registry I of the Intercontinental Cooperative ITP Study Group (ICIS).

    Science.gov (United States)

    Tamminga, Rienk; Berchtold, Willi; Bruin, Marrie; Buchanan, George R; Kühne, Thomas

    2009-07-01

    In children, one-third of immune thrombocytopenic purpura (ITP) patients follow a chronic course. The present study investigated whether treatment with intravenous immunoglobulin (IVIG) at the time of diagnosis of ITP is of prognostic significance, using data from 1984 children entered in Registry I of the Intercontinental Cooperative ITP Study Group. A matched pairs analysis compared children with thrombocytopenia (platelet count or =50 x 10(9)/l at that time point, the former group was less often treated with IVIG than with steroids (P = 0.02). Prospective studies are required to further explore this potential effect of IVIG.

  8. Role of protein tyrosine phosphatases in regulating the immune system: implications for chronic intestinal inflammation.

    Science.gov (United States)

    Spalinger, Marianne R; McCole, Declan F; Rogler, Gerhard; Scharl, Michael

    2015-03-01

    Current hypothesis suggests that genetic, immunological, and bacterial factors contribute essentially to the pathogenesis of inflammatory bowel disease. Variations within the gene loci encoding protein tyrosine phosphatases (PTPs) have been associated with the onset of inflammatory bowel disease. PTPs modulate the activity of their substrates by dephosphorylation of tyrosine residues and are critical for the regulation of fundamental cellular signaling processes. Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses and finally for maintaining intestinal homeostasis. These observations have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly more susceptible to intestinal and systemic inflammation and feature alterations in innate and adaptive immune responses. PTPN22 controls inflammatory signaling in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion pattern and autophagosome formation. PTPN22 deficiency in vivo results in more severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase-induced cytokine secretion but limits secretion of nuclear factor κB-associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also associated with increased colitis severity in vivo. In summary, dysfunction of those PTPs results in aberrant and uncontrolled immune responses that result in chronic inflammatory conditions. This way, it becomes more and more evident that dysfunction of PTPs displays an important factor in the pathogenesis of chronic intestinal inflammation, in particular inflammatory bowel disease.

  9. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    Science.gov (United States)

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease.

  10. Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.

    Science.gov (United States)

    Roque-Cuéllar, M C; Sánchez, B; García-Lozano, J R; Praena-Fernández, J M; Núñez-Roldán, A; Aguilar-Reina, J

    2011-10-01

    It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.

  11. Active von Willebrand factor in thrombotic thrombocytopenic purpura and malaria

    NARCIS (Netherlands)

    Groot, E.

    2009-01-01

    Thrombotic thrombocytopenic purpura (TTP) and malaria are two diseases of distinct origin. TTP is a rare disorder caused by a deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13. Malaria is a poverty-related disease caused by protozoan parasites from the genus Plasmodium. TTP an

  12. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    Science.gov (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  13. PATHOGENETIC PROPERTIES OF IMMUNE STATUS AT CHRONIC VIRAL HEPATITIS B AND C IN CHILDREN

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    Rikalo N.A.

    2015-05-01

    Full Text Available In pathogenesis of chronic viral hepatitis (CVH B and C in children, there are distinct immune disorders. Purpose: to provide the pathogenic characterization of parameters of cellular and humoral immunity in children with CVH B and C, depending on the phase of viral replication and inflammatory activity. Materials and methods. An immunological study of peripheral blood of 50 children with CVH B and C, aged 1 to 18 years prior to the appointment of a specific antiviral treatment were conducted. We determined the CD3+, CD4+, CD8 +, CD16+, CD22+, CD25+ cell’s population and concentration of IgA, IgM and IgG. Results and discussion. The significant decrease of CD3+ (in 10,3 % and CD4+ (in 22% in the phase of viral replication, indicating a persistent shortage of cellular immunity were established. The increase of CD8+ (in 12,5% indicate the activation of cytotoxic reactions. In patients with the virus in the phase of integration or latent stage population of CD16+ were reduced in 31%, indicating inhibition of cytotoxic responses aimed at the destruction of virus-infected cells. The immune disorders in children with CVH B and C from the phase of viral replication and inflammatory activity in the liver was proven. Since the phase of replication and the increase of the activity of inflammation was an increase of CD8+, indicating activation of cytotoxic reactions and causes progressive destruction of hepatocytes. Conclusions: 1. The immune disorders in children with CVH B and C in phase of viral replication are proven. So, there is an increase CD8 +, which indirectly indicates the activation of cytotoxic reactions in the phase of viral replication. With the growth of virus replication activity was significantly intensified the ratio of CD4+/CD8+. This proves that is situ populations of CD4+ could positively regulate the activity of CD8+ at CVH B and C. 2. The increase of the activity of inflammation occurs a significant increase in CD8+ and CD16

  14. Characterization of the innate immune response to chronic aspiration in a novel rodent model

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    Lin Shu S

    2007-11-01

    Full Text Available Abstract Background Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. Methods Gastric fluid or normal saline was instilled into the left lung of rats (n = 48 weekly for 4, 8, 12, or 16 weeks (n = 6 each group. Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. Results Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. Conclusion This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.

  15. An investigation of the general immune status and specific immune responsiveness to retinal-(S)-antigen in patients with chronic posterior uveitis.

    Science.gov (United States)

    Froebel, K S; Armstrong, S S; Cliffe, A M; Urbaniak, S J; Forrester, J V

    1989-01-01

    Immunological abnormalities in endogenous posterior uveitis are widely reported but difficult to verify. We have therefore studied several immunological parameters in 14 patients with chronic posterior uveitis and compared the results with 14 healthy controls. Both the general immune status and the specific immune responsiveness to retinal S-antigen have been investigated. Results for the patient group as a whole were not significantly different from the control group. However the patients with severe eye disease (n = 4) had a reduced proliferative response to streptokinase-streptodornase antigen and two further individuals showed a general deficiency in functional cell mediated immunity. Circulating T-helper cells were marginally but not significantly reduced in patients. Responsiveness to bovine retinal S-antigen varied to a similar degree in both the patient and control groups. These findings indicate that, although severe uveitis may be associated with functional defects in cellular immunity in certain cases, in general the measurement of immune responsiveness of peripheral blood lymphocytes is unlikely to aid in the diagnosis or management of chronic posterior uveitis.

  16. 儿童慢性特发性血小板减少性紫癜与幽门螺杆菌感染的临床研究%CLINICAL STUDY ON CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA AND HELICOBACTOR PYLORI IN CHILDREN

    Institute of Scientific and Technical Information of China (English)

    武国霞; 彭建霞; 张建菊; 武建辉; 任蓉

    2012-01-01

    [Objective] To investigate the relationship of chronic idiopathic thrombocytopenic purpura (cITP) and heli-cobactor pylori (HP) in children, and observe the clinical effect on HP eradiating therapy in children with cITP. [Methods] Children with cITP were delected by 13C urea breath teat. 14 children, who had positive results, were randomly divided into study group (n = 9) and control group (n = 5). The children were treated with immunotherapy and HP eradiating therapy in study group, the children were only treated with immunotherapy in control group. Clinical effects and the platelets before treatment and in the 7th day, 1st month, 2nd month and 3rd month after treatment were compared between groups. [Results] 14 of 66 children with cITP were positive for HP infection (21.2%). The clearances of HP were achieved in 7 out of 9 children with FTP in study group (77.8%). The analysis showed the platelets in the study group were higher than in the control group (P < 0.01) in the 7ui day, 1st month, 2nd month, 3rd month after treatment. The analysis of clinical effects of children showed the study group were better than the control group (P < 0.05). [Conclusion] The study had shown the prevalencde of HP infection in cITP children was 21.2%, the bacterium eradication were obtained in 7 of 9 HP positive children (77.8%) in study group. It is helpful to increase the platelets count and get clinical effects in cITP children combined with HP eradication treatment%[目的]探讨儿童慢性特发性血小板减少性紫癜(cITP)与幽门螺杆菌(HP)的关系,观察根除HP对儿童cITP的疗效.[方法]对cITP患儿进行13℃尿素呼吸试验检测,将确诊HP感染的14例患儿随机分成研究组(9例)和对照组(5例).研究组采用免疫治疗加根除HP治疗,而对照组只采用免疫治疗,比较两组治疗前以及治疗后d7、第1,2,3月血小板的数目和临床效果.[结果]66例cITP患儿中有HP感染14例(21.2%),研究组的9例中,其中7

  17. Trypanosoma cruzi: dehydroepiandrosterone (DHEA) and immune response during the chronic phase of the experimental Chagas' disease.

    Science.gov (United States)

    Caetano, Leony Cristina; Santello, Fabricia Helena; Del Vecchio Filipin, Marina; Brazão, Vânia; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado Júnior, José Clóvis

    2009-07-07

    Dehydroepiandrosterone (DHEA) has long been considered as a precursor for many steroid hormones. It also enhances the immune responses against a wide range of viral, bacterial, and parasitic pathogens. The aims of this work were to evaluate the influences of exogenous DHEA treatment on Wistar rats infected with the Y strain of Trypanosoma cruzi during the acute and its influence on the chronic phase of infection. Animals were subcutaneous treated with 40 mg/kg body weight/day of DHEA. DHEA treatment promoted increased lymphoproliferative responses as well as enhanced concentrations of NO and IL-12. So, we point in the direction that our results validate the utility of the use of DHEA as an alternative therapy candidate against T. cruzi.

  18. [The participation of neutrophilic mechanisms in the pathogenesis of chronic elevated blood immune complexes].

    Science.gov (United States)

    Bidiuk, M M; Chop'iak, V V; Liubinets', L A; Pavlovich, S I; Nykytiuk, H P; Porokhovs'ka, Z S

    1997-01-01

    For reproduction of chronic hyperimmunocomplexemia model the classic Cochrane C. G., 1973 elaboration was used. The circulating immune complexes (CIC) were identified by precipitation methods, and fixated--by immunofluorescent in endothelium reproduction of aorta, and their clearance organs--liver and spleen. The estimation of neutrophil status was carried out according to rosette-forming neutrophils ability--by latex, zimosane, mieloperoxidasa, NST tests. The growth of large and middle CIC in vessel bed was estimated, their fixation in aorta bifurcation, and also on liver and spleen calls, but their intensivity is less, comparing to aorta endothelium. The neutrophil status was characterised by O-neutrophils growth, strengthening of capturing macrophages function, considerable activation of fermentative polynuclear systems, although reserve possibilities in them grew in less degree. Morphologic investigations allow to speak mediatingly about neutrophils participation in endotheliocytes damage, and also about their ability to secure the mononuclear cells further participation in damaging of aorta walls and partially of liver and spleen.

  19. Chronic activation of the innate immune system may underlie the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Bruce Bartholow Duncan

    2001-05-01

    Full Text Available CONTEXTO: The metabolic syndrome is characterized by a clustering, in free-living populations, of cardiovascular and diabetes risk factors generally linked to insulin resistance, obesity and central obesity. Consonant with the well-established inflammatory pathogenesis of atherosclerotic disease, the metabolic syndrome is now being investigated in relation to its inflammatory nature. OBJETIVO: We present cross-sectional findings demonstrating that markers of inflammation correlate with components of the metabolic syndrome, and prospective findings of the ARIC Study indicating that markers of inflammation and endothelial dysfunction predict the development of diabetes mellitus and weight gain in adults. We present biological evidence to suggest that chronic activation of the innate immune system may underlie the metabolic syndrome, characterizing the common soil for the causality of type 2 diabetes mellitus and cardiovascular disease. CONCLUSIONS: Better understanding of the role of the innate immune system in these diseases may lead to important advances in the prediction and management of diabetes and cardiovascular disease.

  20. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    Science.gov (United States)

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar

    2016-02-01

    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.

  1. Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?

    Science.gov (United States)

    Taraseviciene-Stewart, Laima; Douglas, Ivor S; Nana-Sinkam, Patrick S; Lee, Jong D; Tuder, Rubin M; Nicolls, Mark R; Voelkel, Norbert F

    2006-11-01

    The alveolar destruction leading to airspace enlargement in patients with end-stage chronic obstructive pulmonary disease (COPD) is frequently progressive, despite smoking cessation. Several laboratories have accumulated data demonstrating the presence of immune cells in bronchial biopsy specimens and lung tissue sections from patients with COPD. Recently, the accumulation of T and B lymphocytes, often forming follicles, in the lung parenchyma from patients with severe COPD has been reported. In addition, it has been postulated that there might be an autoimmune component to COPD. T-cell receptor analysis has provided data consistent with the concept of T-cell clones in the lung tissue from patients with COPD. Against this background, we developed a model of autoimmune emphysema in adult rats. Based on published data showing that immunization of mice with human umbilical vein endothelial cells (HUVECs) causes production of anti-vascular endothelial growth factor (VEGF) receptor II (KDR) antibodies, and our own data indicating that administration of a VEGF receptor blocker in adult rats causes emphysema, we reasoned that intraperitoneal injection of HUVECs in rats would generate both anti-VEGF receptor antibodies and emphysema. Indeed, intraperitoneal injection of HUVECs caused emphysema. We further explored the autoimmune nature of this model, identified KDR antibodies in the serum of HUVEC-immunized rats, and injected serum from the emphysematous rats into naive rats and mice, which resulted in emphysema. Presently, we are in the process of investigating whether cigarette smoke extract causes emphysema. We recently identified anti-endothelial cell antibodies in the serum of patients with end-stage emphysema.

  2. Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

    Science.gov (United States)

    Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

    2014-05-01

    Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

  3. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection

    Directory of Open Access Journals (Sweden)

    Masachika Senba

    2012-10-01

    Full Text Available Human papillomavirus (HPV has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-kB in cervical and penile cancers suggests that NF-kB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-kB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  4. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy

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    Pooja Sikka

    2013-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange.

  5. Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia.

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    Mohammad Hojjat-Farsangi

    Full Text Available ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients.Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9 and healthy donors (n = 6. IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay.The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05.ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.

  6. The Immune Protective Effect of the Mediterranean Diet against Chronic Low-grade Inflammatory Diseases

    Science.gov (United States)

    Casas, Rosa; Sacanella, Emilio; Estruch, Ramon

    2016-01-01

    Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as protective against several diseases associated with chronic low-grade inflammation such as cancer, diabetes, obesity, atherosclerosis, metabolic syndrome and cognition disorders. The adoption of this dietary pattern could counter the effects of several inflammatory markers, decreasing, for example, the secretion of circulating and cellular biomarkers involved in the atherosclerotic process. Thus, the aim of this review was to consider the current evidence about the effectiveness of the MedDiet in these chronic inflammatory diseases due to its antioxidant and anti-inflammatory properties, which may not only act on classical risk factors but also on inflammatory biomarkers such as adhesion molecules, cytokines or molecules related to the stability of atheromatic plaque. PMID:25244229

  7. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    Science.gov (United States)

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  8. Immune function of erythrocytes in patients with chronic venous insufficiency of the lower extremities

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lan; ZHANG Bai-gen; ZHANG Ji-wei; ZHANG Hao

    2007-01-01

    Background The influence of inflammatory processes has been one of the hot topics in discussions of the etiology of chronic venous insufficiency(CVI).Erythrocytes are very important in controlling inflammatory immunity and innate immune reactions.The purpose of this study was to analyze the correlation between the development of CVI and the change of CD35,Fy6 on erythrocytes,and interleukin-8(IL-8) levels.Methods A group of 43 patients with CVI were studied in parallel with 8 healthy individuals serving as centrol subjects.Control subjects were those with normal findings on lower extremity duplex examinations.We used an erythrocyte flow cytometer to examine the expression of both CD35 and Fy6 on red blood cells,and an enzyme-linked immunosorbent assay analysis method to measure plasma IL-8 levels.We also analyzed the change of IL-8 levels under the influence of erythrocytes using a modified method of the hemaimmune reaction.Results Compared with normal centrol subjects,CD35 expression increased significantly among patients with CVI classified as C4 without lipodermatosclerosis,but tended to decrease and reach the lowest level among patients classified as C5-C6.Fy6 expression increased significantly among patients in the early stages of CVI,but tended to decrease remarkably among patients classified as C5-C6.The inflammatory response intensified at the C5-C6 classification,where high levels of IL-8 coexisted with a low expression of Fy6.The increase in IL-8 in the CVI group was higher than in the control group in association with the complete blood cells,regardless of the presence of erythrocytes,when inactive tumour cells were added,whereas the level of IL-8 in the CVI group was significantly lower than in the control group.Conclusions Abnormalities of erythrocyte innate immunity represents a fundamental derangement in CVI.These inadequate inflammatory responses may lead to local tissue and microvascular damage of the lower extremity.

  9. Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiological disorders in rats

    Science.gov (United States)

    Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.

    rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.

  10. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

    Science.gov (United States)

    Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C. H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

    2017-01-01

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. PMID:28165464

  11. Effects of Rapamycin Combined with Low Dose Prednisone in Patients with Chronic Immune Thrombocytopenia

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    Jiaming Li

    2013-01-01

    Full Text Available We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP. Eighty-eight patients were separated into the control (cyclosporine A plus prednisone and experimental (rapamycin plus prednisone groups. The CD4+CD25+CD127low regulatory T (Treg cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR was similar in both groups (experimental group versus control group: 58% versus 62%, P=0.70. However, sustained response (SR was more pronounced in the experimental group than in the control group (68% versus 39%, P<0.05. Both groups showed similar incidence of adverse events (7% versus 11%, P=0.51. As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P<0.001; however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.

  12. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

    Directory of Open Access Journals (Sweden)

    Broderick Gordon

    2012-09-01

    Full Text Available Abstract Background As Chronic Fatigue Syndrome (CFS has been known to follow Epstein-Bar virus (EBV and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM. We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70, 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

  13. IMMUNE AND CYTOKINE STATUS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA RECEIVING ALEMTUZUMAB

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    M. N Khorobrykh

    2010-01-01

    Full Text Available In present work, we studied cytokine levels and performed analysis of some immunologic parameters in the patients with chronic lymphocytic leukemia (CLL before and after treatment with monoclonal anti-CD52 antibody (alemtuzumab. In comparison with a control group, the CLL patients before alemtuzumab treatment showed a significant decrease in relative contents of CD3+ and CD4+ lymphocytes, CD4+/CD8+ T cells, diminished IFNγ and IL-4 levels, and a trend for TNFα increase. After ceasing the alemtuzumab treatment, the patients with CLL exhibited a significant decrease in absolute amounts of mature T-lymphocytes, CD4+, CD8+, CD20+ cells, as well as decreased relative contents of CD16+ lymphocytes. A sufficient post-treatment drop of serum IL-2 concentrations and a trend for serum TNFα and IFNγ decrease were also observed, as compared with pre-treatment values. The changes revealed may be connected with an additional immunosuppressive effect of alemtuzumab. The dynamics of cytokine levels and immunological parameters associated with alemtuzumab treatment is indicative for a weakening of cell-mediated immunity, thus resulting into a potential risk of infectious complications.

  14. Chronic transplantation immunity in newts: temperature susceptibility of an effector phase in allo-skin graft rejection.

    Science.gov (United States)

    Kinefuchi, Kenjiroh; Kushida, Yoshihiro; Johnouchi, Masato; Shimizu, Yuiko; Ohneda, Hikaru; Fujii, Masato; Hosono, Masamichi

    2011-07-01

    Urodele amphibians are unique due to their greatly reduced immune responsiveness compared to bony fishes, which show acute immune responsiveness. In newts, the mean survival time of allogenic skin grafts in the transplantation immunity was 48.8 ± 8.3 days at 25°C, suggesting that it occurs in a chronic manner. The graft rejection process was categorized into three stages: a latent stage with frequent blood circulation, or the immune induction phase; a vascular stoppage stage with dominant infiltrating cells of T cells; and a rejection stage showing the change of the dominant cells to monocytes/macrophages, probably as effector cells, tetntatively referred to as the immune effector phase. The immune induction phase is susceptible to the cyclophosphamide (CY) mitosis inhibitor, but not to a temperature shift from 18 to 27°C, while the immune effector phase is susceptible to temperature shifts, but not CY-treatment, although the temperature shift failed to shorten the graft survival time to less than 25 days, which nearly equals that of the secondary set of grafts where the lack of complete blood circulation is remarkable and graft rejection is resistant to CY-treatment. In contrast, a very low temperature (5-10°C) completely prevented effector generation in newts; in frogs, however, it is reported that such low temperatures did not prevent the generation of effectors. Taken together, these data suggest that chronic responses in newts are due to effector cells other than cytotoxic T cells; possible effector cells are discussed.

  15. Virological and morphological relationships in the phases of the immune control and reactivation in patients with chronic hepatitis B

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    I. A. Gabdrakhmanov

    2015-01-01

    Full Text Available Objective: To evaluate relationships between virological and morphological data in patients with chronic hepatitis B in phase immune control and reactivation.Materials and methods: The study involved 46 patients with chronic hepatitis B, indicators defined were content of surface antigen and hepatitis B virus DNA in the peripheral blood, the level of covalently closed circular HBV DNA in liver tissue and fibrosis stage and histological activity index (METAVIR.Results: The study found a direct correlation between the level of covalently closed circular DNA in liver puncture biopsies (number of copies per cell and quantitative content of HBsAg in serum (r = 0,51, p = 0,03 in patients with chronic hepatitis B in phase immune control. Also in the immune control phase a direct correlation between the HBV DNA and the level of HBsAg in serum (r = 0.79, p = 0.0001 is shown. The level of covalently closed circular HBV DNA in liver puncture biopsy specimens did not differ in patients with chronic hepatitis B in the phase of immune control in the phase of reactivation (1,02 ± 0,01 copies / cell and 1,03 ± 0,03 copies / cell, p = 0.72. The index of histological activity and fibrosis were not correlated with any of the investigated virological indicator.Conclusion: Results of the study emphasized the complexity and ambiguity of the relationships between both virological and morphological indicators in patients with chronic hepatitis B, determined the direction for further study (in particular the assessment of the epigenetic regulation of the synthesis of circular covalently closed DNA, as well as set the stage for improving the principles of dynamic observing the patients with chronic hepatitis B in a phase of immune control.

  16. Influence of supplementary immunization activities for adults dynamics of chronic disease HBV-infection and its outcomes

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    S. V. Baramzina

    2014-01-01

    Full Text Available Purpose: to evaluate the effect of additional vaccination of adult HBV- infection years 2007–2010 on the incidence of chronic hepatitis B and its outcomes on the example of the Kirov region.Materials and Methods: the evaluation of epidemiological features process in patients with chronic HBV infection in adults, depending on the vaccination carried out on the basis of official data Rospotrebnadzora in Russia and Kirov region on incidence of infectious disease for the period 1999–2012. Diagnosis of chronic hepatitis B was based on clinical and biochemical, instrumental, virological data. Structure outcomes of chronic hepatitis B was studied in 295 patients aged 18–75 years who were hospitalized in the department of viral hepatitis Kirov infectious diseases hospital in 2006–2010.Results: In the Kirov region tended to decrease the incidence of chronic hepatitis B in adults. Additional adult vaccination against hepatitis B has not led to the expected significant decrease of the number of patients with chronic forms. One reason for this is the low (20,3–64% of the adult population immunization coverage. Chronic HBV- monoinfected was observed in 17.1% , cirrhosis in the outcome of chronic hepatitis B in 5,4% of cases, in hospital mortality from complications of HBV- cirrhosis was 0,7%. Association virus C and D have increased the total cohort, compared to a mono- infection by 3,8% and 0,5% lethality.Conclusion: Additional adult vaccination against hepatitis B in the area has led to a slight decrease in the overall incidence of chronic hepatitis B, but has not reduced the incidence of adverse events – cirrhosis and liver- mediated lethality.

  17. Immunity

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920630 Effects of the spleen on immunestate of patients with gastric cancer.QIUDengbo (仇登波), et al. Dept General Surg,Union Hosp, Tongji Med Univ, Wuhan, 430022.Natl Med J China 1992; 72(6): 334-337. For analysing the effects of the spleen on im-mune state of gastric cancer patients.T-lym-

  18. Sociodemographic influences on immunization of children with chronic neurological disorders in Enugu, Nigeria

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    J.C. Okoro

    2015-01-01

    Conclusion: Children with obvious neurological deficits whose mothers have low educational attainment are at risk of low immunization coverage. It is recommended that healthcare workers should assess the immunization status of children with CND at every opportunity. Female education and empowerment should be encouraged as a means of enhancing the immunization coverage of these children.

  19. CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

    Science.gov (United States)

    Barathan, Muttiah; Mohamed, Rosmawati; Vadivelu, Jamuna; Chang, Li Yen; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Sigamani, Panneer; Saeidi, Alireza; Ram, M Ravishankar; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

    2017-03-01

    Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.

  20. Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

    Science.gov (United States)

    Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

    2015-06-01

    Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD.

  1. 大剂量地塞米松对免疫性血小板减少性紫癜患者浆样树突状细胞功能及Toll样受体9表达的影响%Effect of high-dose dexamethasone on the function and TLR-9 expression of plasmacytoid dendritic cells in patients with immune thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    王莉; 张连生; 柴晔; 曾鹏云; 吴重阳

    2012-01-01

    To investigate the effect of high-dose dexamethasone on the function and TLR-9 expression of plasmacytoid dendritic cells in the patients with immune thrombocytopenic purpura. Method: Fifteen newly diagnosed patients with immune thrombocytopenic purpura received high dose(HD)DXM at single daily doses of 40 mg for 4 consecutive days. The peripheral blood plasmacytoid dendritic cells isolated from 13 remission patients and 15 normal controls were separated by immunomagnetie beads and then induced by CpG-OND2216 for 24 hours. The levels of IFN-α,IL-6 and TNF-αin the supernatant were detected by enzyme linked immunosorbent assay. The expression of TLR9 mRNA of pDCs was detected by Real-time quantitative PCR. Result: In ITP patients, the levels of IFN-α.IL-6 and TNF-αproduced by pDCs were significantly higher compared with those in normal controls and in treated group(P0. 05). The expression of TLR9 mRNA of pDCs in untreated group were significantly higher than control group(P0. 05). Conclusion: pDCs may play important role in ITP by their Toll-like receptor 9 and cytokines secretion (Dexamethasone may reduce the expression of TLR9, inhibit pDC function,and thus play a therapeutic role.%目的:研究大剂量地塞米松对免疫性血小板减少性紫癜(ITP)患者浆样树突状细胞(pDCs)功能及Toll样受体9表达的影响.方法:15例初诊的ITP患者给予地塞米松40 mg/d,连用4d.采用免疫磁珠分离法体外分离15例正常对照及13例治疗有效患者治疗前后外周血中浆细胞样树突状细胞(pDCs),用CPG-ODN 2216刺激外周血pDCs并与之共培养24 h,采用酶标记免疫吸附(ELISA)方法检测上清中IFN-α、IL-6、TNF-α的含量;实时定量聚合酶链反应(RT-PCR)检测pDCs的TLR9 mRNA表达量.结果:①治疗前pDCs产生IFN-α、IL-6、TNF-α细胞因子的水平[(960.83±164.65)pg/ml,(156.15土39.89) pg/ml,(137.31土35.44)pg/ml]明显高于正常对照组[(616.67±105.98) pg/ml,(89.13±21.48) pg/ml,(88.53±25

  2. Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity

    Science.gov (United States)

    Okada, Satoshi; Puel, Anne; Casanova, Jean-Laurent; Kobayashi, Masao

    2016-01-01

    Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC. In contrast, CMC disease (CMCD) is typically defined as CMC in patients in the absence of any other prominent clinical signs. This definition is not strict; thus, CMCD is currently used to refer to patients presenting with CMC as the main clinical phenotype. The etiology of CMCD is not related to genes that cause severe combined immunodeficiency or combined immunodeficiency, nor to genes responsible for Syndromic CMC. Four genetic etiologies, AR IL-17 receptor A, IL-17 receptor C and ACT1 deficiencies, and AD IL-17F deficiency, are reported to underlie CMCD. Each of these gene defects directly has an impact on IL-17 signaling, suggesting their nonredundant role in host mucosal immunity to Candida. Here, we review current knowledge focusing on IL-17 signaling and the genetic etiologies responsible for, and associated with, CMC. PMID:28090315

  3. Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?

    NARCIS (Netherlands)

    E.H.C.J. Buster (Erik); H.L.A. Janssen (Harry)

    2006-01-01

    textabstractThe availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be

  4. Chronic psychosocial stress: does it modulate immunity to the influenza vaccine in Hong Kong Chinese elderly caregivers?

    Science.gov (United States)

    Wong, Samuel Yeung Shan; Wong, Chun Kwok; Chan, Frank Wan Kin; Chan, Paul K S; Ngai, Karry; Mercer, Stewart; Woo, Jean

    2013-08-01

    Previous studies evaluated the effects of psychosocial stress on influenza vaccine responses. However, there were methodological limitations. This study aims to determine whether chronic stress is associated with poorer influenza-specific immune responses to influenza vaccines in Hong Kong Chinese elderly people. This is a prospective study with a 12-week follow-up. Subjects were recruited from government general out-patient clinics, non-government organizations, and public housing estates in Hong Kong. Participants include 55 caregivers of spouses with chronic conditions that impaired their activities of daily living and 61 age- and sex-matched non-caregivers. A single-dose trivalent influenza vaccine was given to all subjects by intramuscular ingestion. Blood samples were collected before vaccination, at 6 weeks, and at 12 weeks after vaccination. Influenza vaccine strain-specific antibody titers were measured by the hemagglutination inhibition method. Lymphocyte subsets were analyzed for ratios and absolute counts, and cytokine concentration were measured by flow cytometry. Validated scales were used to assess psychological (depressive symptoms, perceived stress, and caregiver strain), social (multidimensional social support scale), and lifestyle factors (physical exercise, cigarette smoking, and alcohol consumption) at baseline prior to vaccination. Demographic and socioeconomic variables were also collected. Albumin levels were measured as an indicator for nutritional status in subjects. Caregivers had statistically significant (p < 0.05) lower cell-mediated immune responses to influenza vaccination at 12 weeks when compared with those of the controls. No differences in humoral immune response to vaccination were observed between caregivers and controls. Hong Kong Chinese elderly who experience chronic stress have a significantly lower cell-mediated immune response to influenza vaccination when compared with non-caregivers.

  5. MiRNA-548ah, a Potential Molecule Associated with Transition from Immune Tolerance to Immune Activation of Chronic Hepatitis B

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    Tong-Jing Xing

    2014-08-01

    Full Text Available Objective: The present study aims to identify the differently expressed microRNA (miRNA molecules and target genes of miRNA in the immune tolerance (IT and immune activation (IA stages of chronic hepatitis B (CHB. Methods: miRNA expression profiles of peripheral blood mononuclear cells (PBMCs at the IT and IA stages of CHB were screened using miRNA microarrays and authenticated using a quantitative real-time polymerase chain reaction (RT-PCR. Gene ontology (GO and the Kyoto encyclopedia of genes and genomes (KEGG were used to analyze the significant functions and pathways of possible target genes of miRNAs. Assays of the gain and loss of function of the miRNAs were performed to verify the target genes in THP-1 cell lines. The luciferase reporter test was used on 293T cells as direct targets. Results: Significantly upregulated miR-548 and miR-4804 were observed in the miRNA microarrays and confirmed by RT-PCR in PBMCs at the IT and IA stages of CHB. GO and KEGG analysis revealed that MiR-548 and miR-4804 could be involved in numerous signaling pathways and protein binding activity. IFNγR1 was predicted as a target gene and validated as the direct gene of MiR-548. Significant negative correlation was found between the miR-548ah and mRNA levels of IFN-γR1 in CHB patients. Conclusions: The abnormal expression profiles of miRNA in PBMCs could be closely associated with immune activation of chronic HBV infection. miR-548, by targeting IFN-γR1, may represent a mechanism that can facilitate viral pathogenesis and help determine new therapeutic molecular targets.

  6. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

  7. AMEGAKARYOCYTIC THROMBOCYTOPENIC PURPURA‎: A FIFTEEN YEAR EXPERIENCE

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    M. Bakhshi

    2006-07-01

    Full Text Available Totally implantable venous access devices (TIVAD or implantable catheter ports are devices which can be implanted subcutaneously. They enable prolonged and repeated access to the vascular system, into the peritoneal cavity or intravertebral space. This device is particularly useful for repeated medical injection, for blood sampling or transfusion of blood and blood derivatives and for total parenteral nutrition (TPN. Although many patients benefit from the insertion of TIVAD without any secondary effects, any surgical implantation can nevertheless lead to complications. ‎In this study, we investigated the advantages and disadvantages of TIVAD catheter in pediatric age group. A total of 94 cases, 2 to 14 years old, were included in our study. We implanted TIVAD in these patients for chemotherapy in 83 cases (88.29%, for prolonged TPN in 6 cases (6.38%, for corticosteroid and antibiotic therapy after ‎Kasai operation in 2 cases (2.12%, for intermittent IV therapy in 2 cases (2.12% and for need to partial parenteral nutrition in 1 case (1.06%. Out of 94 cases, 14 cases (15% had some kind of complications and 80 cases (85% had no complication. There was no mortality. Most patients and their parents (82 cases, 87.23% were satisfied from TIVAD. ‎It seems that TIVAD can be a useful device for many chronic patients who need an IV access for multiple injections.

  8. A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Arimoto M

    2012-03-01

    Full Text Available Miyoko Arimoto1, Yutaka Komiyama2, Fumiko Okamae1, Akemi Ichibe1, Setsuko Teranishi1, Hirohiko Tokunaga1, Keiko Nakaya3, Michie Fujiwara3, Manabu Yamaoka4, Shuji Onishi4, Rie Miyamoto5, Naoto Nakamichi5, Shosaku Nomura51Blood Transfusion Unit, Kansai Medical University Takii Hospital, 2Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 3Clinical Medical Technology Unit, Kansai Medical University Takii Hospital, 4Blood Transfusion Unit, Kansai Medical University Hirakata Hospital, 5First Department of Internal Medicine, Kansai Medical University, Moriguchi, JapanAbstract: Thrombotic thrombocytopenic purpura (TTP is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, acute pancreatitis, plasma exchange

  9. Effect of adefovir dipivoxil on T cell immune function in the treatment of chronic hepatitis B and hepatocirrhosis

    Science.gov (United States)

    Tian, Liting; Fu, Qilin; Huang, Fu

    2016-01-01

    The aim of the present study was to investigate the T cell immune function in chronic hepatitis B hepatocirrhosis patients at the compensated and decompensated stage following treatment with adefovir dipivoxil. A total of 104 patients diagnosed with hepatitis B hepatocirrhosis during the period from October 2013 to October 2014 were enrolled in the study. Among the cases, there were 56 cases at compensated stage, and another 48 at decompensated stage. Adefovir dipivoxil was administered for antiviral therapy (10 mg/time, 1 time/day, for a total of 24 weeks), and we compared the virus disappearance rate, liver function improvement and T cell immune function between the two groups before and after treatment. The difference between the virus disappearance rate in the two groups was not statistically significant (P>0.05). The decreased level of ALT decrease in the compensated group was significantly higher than that in the decompensated group, while the increased level of albumin in the compensated group was significantly higher as well. The differences showed statistical significance (P0.05). Adefovir dipivoxil treatment can improve T cell immune function at the compensated and decompensated stages in chronic hepatitis B hepatocirrhosis patients. This may be associated with virus disappearance and liver function improvement.

  10. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement

    Directory of Open Access Journals (Sweden)

    Toussirot E

    2013-04-01

    Full Text Available Éric Toussirot,1–4 Fabrice Michel,5 Matthieu Béreau,6 Delphine Binda1,7 1Clinical Investigation Center – Biotherapy CBT-506, University Hospital of Besançon, Besançon, France; 2Department of Rheumatology, University Hospital of Besançon, Besançon, France; 3Department of Therapeutics, University of Franche-Comté, Besançon, France; 4Equipe d'Acceuil 4266 Pathogens and Inflammation, Structure Fédérative de Recherche–Fédération de Recherche 4234, University of Franche-Comté, Besançon, France; 5Department of Physical Medicine and Rehabilitation, University Hospital of Besançon, Besançon, France; 6Department of Neurology, University Hospital of Besançon, Besançon, France; 7Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1098, Blood Transfusion Center, Besançon, France Abstract: Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn's disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn's disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-α inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of

  11. Rituximab treatment for symptomatic chronic ITP

    NARCIS (Netherlands)

    Tamminga, Rienk Y. J.; Bruin, Marrie C. A.

    2006-01-01

    About 20% of the children diagnosed with acute idiopathic thrombocytopenic purpura (ITP) will run a chronic course. Only in a minority of these, platelet-count-enhancing treatments are indicated. Most treatment options are directed at decreasing platelet destruction including corticosteroids, intrav

  12. Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

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    Vernon Suzanne D

    2008-09-01

    Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

  13. Immune evasion activities of accessory proteins Vpu, Nef and Vif are conserved in acute and chronic HIV-1 infection.

    Science.gov (United States)

    Mlcochova, Petra; Apolonia, Luis; Kluge, Silvia F; Sridharan, Aishwarya; Kirchhoff, Frank; Malim, Michael H; Sauter, Daniel; Gupta, Ravindra K

    2015-08-01

    Heterosexual HIV-1 transmission has been identified as a genetic bottleneck and a single transmitted/founder (T/F) variant with reduced sensitivity to type I interferon initiates productive infection in most cases. We hypothesized that particularly active accessory protein(s) may confer T/F viruses with a selective advantage in establishing HIV infection. Thus, we tested vpu, vif and nef alleles from six T/F and six chronic (CC) viruses in assays for 9 immune evasion activities involving the counteraction of interferon-stimulated genes and modulation of ligands known to activate innate immune cells. All functions were highly conserved with no significant differences between T/F and CC viruses, suggesting that these accessory protein functions are important throughout the course of infection.

  14. Effects of chronic produced water exposure on the expression of some immune-related genes of juvenile Atlantic cod

    Energy Technology Data Exchange (ETDEWEB)

    Perez Casanova, J.; Hamoutene, D.; Samuelson, S.; Burt, K.; King, T. [Fisheries and Oceans Canada, St. John' s, NL (Canada); Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada)

    2010-07-01

    This study assessed the impacts of exposure to processed water produced by offshore oil operators on immune-related genes of juvenile Atlantic cod exposed to processed water for a period of 22 weeks. The study investigated the influence of processed water concentrations on growth parameters; food consumption; plasma cortisol; respiratory burst activity (RB); and mRNA expression. The study showed that the RB of circulating leukocytes was significantly elevated. Significant up-regulation of the mRNA expression of microglobulin, immunoglobulin light chain, and interleukins was observed in some fish. The down-regulation of the interferon stimulated gene was also observed. The study indicated that chronic exposure to significant amounts of processed water causes modulations of the immune system of juvenile Atlantic cod.

  15. Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B

    Science.gov (United States)

    Korolowicz, Kyle E.; Iyer, Radhakrishnan P.; Czerwinski, Stefanie; Suresh, Manasa; Yang, Junming; Padmanabhan, Seetharamaiyer; Sheri, Anjaneyulu; Pandey, Rajendra K.; Skell, Jeffrey; Marquis, Judith K.; Kallakury, Bhaskar V.; Tucker, Robin D.; Menne, Stephan

    2016-01-01

    SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway. PMID:27552102

  16. Life-threatening autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura: successful seletive splenic artery embolization

    Directory of Open Access Journals (Sweden)

    matteo molica

    2016-04-01

    Full Text Available Selective splenic artery embolization (SSAE is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP and warm auto-immune hemolytic anemia (AIHA both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy.

  17. Life-Threatening Autoimmune Hemolytic Anemia and Idhiopatic Thrombocytopenic Purpura. Successful Selective Splenic Artery Embolization

    Science.gov (United States)

    Molica, Matteo; Massaro, Fulvio; Annechini, Giorgia; Baldacci, Erminia; D’Elia, Gianna Maria; Rosati, Riccardo; Trisolini, Silvia Maria; Volpicelli, Paola; Foà, Robin; Capria, Saveria

    2016-01-01

    Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy. PMID:27158433

  18. Vaccinations in adults with chronic inflammatory joint disease: Immunization schedule and recommendations for patients taking synthetic or biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Morel, Jacques; Czitrom, Séverine Guillaume; Mallick, Auriane; Sellam, Jérémie; Sibilia, Jean

    2016-03-01

    The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research).

  19. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

    Science.gov (United States)

    Vilajeliu, Alba; Sequera, Víctor-Guillermo; García-Basteiro, Alberto L; Sicuri, Elisa; Aldea, Marta; Velasco, César; Bayas, José M

    2016-09-01

    Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

  20. Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura

    NARCIS (Netherlands)

    Houwerzijl, Ewout Johan

    2008-01-01

    In this thesis mechanisms of thrombocytopenia (a low number of platelets) in patients with myelodysplastic syndromes (MDS) or idiopathic thrombocytopenic purpura (ITP) were investigated. Thrombocytopenia can cause serious bleeding complications and elucidation of the underlying pathophysiology of th

  1. Correlation of thyroid hormone levels and immune function state with the illness in patients with chronic urticaria

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yan Sun; Guang-Zhong Yang; Qing-Xiang Li; Yao Wang

    2016-01-01

    Objective:To study the correlation of thyroid hormone level and immune function state with the illness in patients with chronic urticaria.Methods:A total of 54 patients with chronic urticaria treated in our hospital between May 2015 and October 2015 were selected as the chronic urticaria group (CU group) of the study, 50 healthy volunteers receiving physical examination in our hospital during the same period were selected as the negative control group (NC group) of the study, serum was collected to determine the content of immunoglobulins, complements, interleukins, thyroid hormone and autoantibodies.Results: Serum C3, C4 and IL-2 content of CU group were significantly lower than those of NC group while IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content were significantly higher than those of NC group; serum TT3, TT4, FT3, FT4, TSAb, TGAb, TPOAb and TMAb content of CU group were significantly higher than those of NC group, negatively correlated with serum C3, C4 and IL-2 content, and positively correlated with serum IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content;serum TSH content was significantly lower than that of NC group, positively correlated with serum C3, C4 and IL-2 content, and negatively correlated with serum IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content.Conclusions: Thyroid autoantibody synthesis and thyroid hormone release increase in patients with chronic urticaria, and the change of thyroid hormone levels and immune function is closely related to the illness.

  2. [Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

    Science.gov (United States)

    Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

    2008-01-01

    There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

  3. Chronic active Epstein-Barr virus infection in an adult with no detectable immune deficiency.

    NARCIS (Netherlands)

    Boer, M. de; Mol, M.J.T.M.; Bogman, M.J.J.T.; Galama, J.M.D.; Raymakers, R.A.P.

    2003-01-01

    INTRODUCTION: Epstein-Barr virus (EBV) establishes lifelong latent infection. In some patients the host-virus balance is disturbed, resulting in a chronic active EBV infection. The following case illustrates the difficulty in diagnosing and treating chronic EBV infection. CASE: A 30-year-old woman w

  4. Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.

    Science.gov (United States)

    Pham, T N Q; Mercer, S E; Michalak, T I

    2009-08-01

    Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-alpha, IFN-gamma and TNF-alpha, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-gamma but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-alpha and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-gamma in CHC, but of IFN-alpha in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells.

  5. Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

    Directory of Open Access Journals (Sweden)

    Joji Nagasaki

    2016-01-01

    Full Text Available The etiologies of secondary idiopathic thrombocytopenic purpura (ITP include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP eradication or corticosteroid treatment, all of the patients’ platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations.

  6. Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Zhang, Qiong-Fang; Shao, Jian-Ying; Yin, Wen-Wei; Xia, Yang; Chen, Ling; Wang, Xing; Hu, Huai-Dong; Hu, Peng; Ren, Hong; Zhang, Da-Zhi

    2016-01-01

    Background Natural killer (NK) cells are the main effective component of the innate immune system that responds to chronic hepatitis B (CHB) infection. Although numerous studies have reported the immune profiles of NK cells in CHB patients, they are limited by inconsistent results. Thus, we performed a meta-analysis to characterize reliably the immune profiles of NK cells after CHB infection, specifically frequency, phenotype, and function. Methods A literature search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center Register of Controlled Trails was performed and 19 studies were selected. The standard mean difference (SMD) and 95% confidence interval (CI) of each continuous variable was estimated with a fixed effects model when I2 NUCs) showed no statistical difference in NK frequency. The activating receptors were upregulated, whereas inhibitory receptors were comparable in the peripheral NK cells of CHB individuals and healthy controls. NK cells of CHB patients displayed higher cytotoxic potency as evidenced by CD107a protein levels and conserved potency to produce interferon-gamma (IFNγ), compared with their healthy counterparts. Conclusion Our results revealed that CHB patients had a lower frequency of NK cells compared with healthy individuals not treatable with antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients showed better cytotoxic potency and conserved IFNγ production. PMID:27513564

  7. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Eugenia Carrillo

    Full Text Available Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system.

  8. A serum microRNA signature is associated with the immune control of chronic hepatitis B virus infection.

    Directory of Open Access Journals (Sweden)

    Maurizia Rossana Brunetto

    Full Text Available BACKGROUND AND AIMS: The virus/host interplay mediates liver pathology in chronic HBV infection. MiRNAs play a pivotal role in virus/host interactions and are detected in both serum and HBsAg-particles, but studies of their dynamics during chronic infection and antiviral therapy are missing. We studied serum miRNAs during different phases of chronic HBV infection and antiviral treatment. METHODS: MiRNAs were profiled by miRCURY-LNA-Universal-RT-miRNA-PCR (Exiqon-A/S and qPCR-panels-I/II-739-miRNA-assays and single-RT-q-PCRs. Two cohorts of well-characterized HBsAg-carriers were studied (median follow-up 34-52 months: a training-panel (141 sera and HBsAg-particles (32 samples from 61 HBsAg-carriers and b validation-panel (136 sera from 84 carriers. RESULTS: Thirty-one miRNAs were differentially expressed in inactive-carriers (IC and chronic-hepatitis-B (CHB with the largest difference for miR-122-5p, miR-99a-5p and miR-192-5p (liver-specific-miRNAs, over-expressed in both sera and HBsAg-particles of CHB (ANOVA/U-test p-values: 8.3 Log10 IU/mL, ρ = -0.732, p<0.001 and HBsAg (3.40, 0.11/5.49 Log10 IU/mL, ρ = -0.883, p<0.001. At multivariate analysis HBV-DNA (p = 0.002, HBsAg (p<0.001 and infection-phase (p<0.001, but not ALT (p = 0.360 correlated with MiR-B-Index. In SVR to Peg-IFN/NUCs MiR-B-Index improved during-therapy and post-treatment reaching IC-like values (5.32, -1.65/10.91 vs 6.68, 0.54/9.53, p = 0.324 beckoning sustained HBV-immune-control earlier than HBsAg-decline. CONCLUSIONS: Serum miRNA profile change dynamically during the different phases of chronic HBV infection. We identified a miRNA signature associated with both natural-occurring and therapy-induced immune control of HBV infection. The MiR-B-Index might be a useful biomarker for the early identification of the sustained switch from CHB to inactive HBV-infection in patients treated with antivirals.

  9. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease.

    Science.gov (United States)

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G

    1976-01-01

    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  10. Targeting immune pathways for therapy in asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Brusselle, Guy; Bracke, Ken

    2014-12-01

    Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic inflammatory diseases of the airways, with differences in etiology, pathogenesis, immunologic mechanisms, clinical presentation, comorbidities, prognosis, and response to treatment. In mild to moderate early-onset allergic asthma, the Th2-driven eosinophilic airway inflammation and the ensuing disease can be well controlled with maintenance treatment with inhaled corticosteroids (ICS). In real-life settings, asthma control can be improved by facilitating adherence to ICS treatment and by optimizing inhaler technique. In patients with uncontrolled severe asthma, old and novel therapies targeting specific immunologic pathways should be added according to the underlying endotype/phenotype. In COPD, there is a high unmet need for safe and effective antiinflammatory treatments that not only prevent exacerbations but also have a beneficial impact on the course of the disease and improve survival. Although several new approaches aim to target the chronic neutrophilic pulmonary inflammation per se in patients with COPD, strategies that target the underlying causes of the pulmonary neutrophilia (e.g., smoking, chronic infection, and oxidative stress) might be more successful. In both chronic airway diseases (especially in more difficult, complex cases), the choice of the optimal treatment should be based not only on arbitrary clinical labels but also on the underlying immunopathology.

  11. Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

    Science.gov (United States)

    Baker, B S; Powles, A V; Malkani, A K; Lewis, H; Valdimarsson, H; Fry, L

    1991-07-01

    The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

  12. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease

    NARCIS (Netherlands)

    Henriet, S.S.V.; Jans, J.; Simonetti, E.R.; Kwon-Chung, K.J.; Rijs, A.J.M.M.; Hermans, P.W.M.; Holland, S.M.; Jonge, M.I. de; Warris, A.

    2013-01-01

    Invasive aspergillosis is a major threat to patients with chronic granulomatous disease (CGD). Fungal pathogenesis is the result of a diminished antifungal capacity and dysregulated inflammation. A deficient NADPH-oxidase complex results in defective phagolysosomal alkalization. To investigate the c

  13. Shared immune and repair markers during experimental toxoplasma chronic brain infection and schizophrenia

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); T.L. Schultz (Tracey L.); W. Kluge (Wolfgang); R.H. Yolken (Robert H.); S. Bahn (Sabine); V.B. Carruthers (Vern B.)

    2016-01-01

    textabstractChronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse m

  14. Immune Modulating Therapy and its Viral Kinetics in Chronic Hepatitis B

    NARCIS (Netherlands)

    M.J. ter Borg (Martijn)

    2008-01-01

    textabstractApproximately 400 million people worldwide are chronically infected with the hepatitis B virus (HBV) and it is estimated that between 500,000 and 1 million people die annually from cirrhosis and hepatocellular carcinoma due to HBV infection.1-3 Despite the availability of safe and effect

  15. Chronic Stress, Depression and Immunity in Spouses of Metastatic Breast Cancer Patients

    Science.gov (United States)

    Mortimer, Jane S. Blake; Sephton, Sandra E.; Kimerling, Rachel; Butler, Lisa; Bernstein, Aaron S.; Spiegel, David

    2005-01-01

    Objective: The objective of this study was to examine how the chronicity of stress affects psychological stress-responses, depressive symptoms, and "in vivo" immunocompetence in spouses of women with metastatic breast cancer. Methods: Participants were 34 spouses of breast cancer patients. Their wives had been living with a diagnosis of…

  16. Defects in host immune function in tree frogs with chronic chytridiomycosis.

    Directory of Open Access Journals (Sweden)

    Sam Young

    Full Text Available The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd has caused mass mortality leading to population declines and extinctions in many frog species worldwide. The lack of host resistance may be due to fungal immunosuppressive effects that have been observed when Bd is incubated with cultured lymphocytes, but whether in vivo host immunosuppression occurs is unknown. We used a broad range of hematologic and protein electrophoresis biomarkers, along with various functional tests, to assess immune competence in common green (Litoria caerulea and white-lipped (L. infrafrenata tree frogs experimentally infected with Bd. Compared with uninfected frogs, Bd infection in L. caerulea caused a reduction in immunoglobulin and splenic lymphocyte responses to antigenic stimulation with sheep red blood cells, along with decreased white blood cell and serum protein concentrations, indicating possible impaired immune response capability of Bd-infected frogs. This is the first in vivo study suggesting that infection with Bd causes multiple defects in systemic host immune function, and this may contribute to disease development in susceptible host species. Although L. infrafrenata failed to maintain Bd infection after exposure, white blood cell and serum globulin concentrations were lower in recovered frogs compared with unexposed frogs, but antigen-specific serum and splenic antibody, and splenic cellular, responses were similar in both recovered and unexposed frogs. This may indicate potential systemic costs associated with infection clearance and/or redirection of host resources towards more effective mechanisms to overcome infection. No clear mechanism for resistance was identified in L. infrafrenata, suggesting that localized and/or innate immune defense mechanisms may be important factors involved in disease resistance in this species.

  17. Analysis of clinical feature of infantile idiopathic thrombocytopenic purpura%婴儿特发性血小板减少性紫癜临床特点分析

    Institute of Scientific and Technical Information of China (English)

    刘小丹; 李学荣; 孙立荣

    2011-01-01

    目的 分析婴儿特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)的特点.方法 从性别、临床表现、实验室检查、治疗效果等方面对77例ITP患儿进行观察和分析评价.结果婴儿组男性占75%,年长儿组男性占60%; 诱因为疫苗接种:婴儿组占28%,年长儿组占4%;诱因为感染:婴儿组为38%,年长儿组为58%;临床表现:婴儿组多见皮肤出血,出血程度较轻,年长儿组多见黏膜出血,或皮肤和黏膜混合出血,出血程度较重;治疗效果:婴儿组治愈+显效者30/32例(94%),年长儿组36/45例(84%),婴儿组无一例发展为慢性型,年长儿组3例发展为慢性型.结论 与年长儿组比较,婴儿组ITP患儿常见于男性,发病诱因主要为感染和免疫接种,出血程度较轻,疗效反应好,起效快,不易发展为慢性.%Objective To analyze the characteristics of infantile idiopathic thrombocytopenic purpura (ITP).Methods Clinical data of 77 ITP inpatients ( including 32 infants and 45 children older than 1 year of age)were observed.Clinical features, manifestations, laboratory findings and the treatment effect were analyzed and evaluated.Results Male accounted for 75% and 60% in infants and older children respectively; 28% of infants vs.4% of older children were induced by immunizations; 38% of infants vs.58% of older children were induced by infections; skin bleeding or mild hemorrhage were most commonly found in infants, while mucosal bleeding, mixed bleeding of skin and mucous membrane and severe hemorrhage were most commonly found in older children; the cure rate of infants was 30/32 (94%) compared with 36/45 (86%) in older children.None of infants vs.3 of older children developed into chronic ITP.Conclusion Infantile ITP preferentially affects boys.It is mainly induced by infection and immunization.It has mild hemorrhage, favorable therapeutic effect and lower susceptibility to chronic ITP.

  18. Peptide vaccination induces profound changes in the immune system in patients with B-cell chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2011-04-01

    Full Text Available Although the immune status of chronic lymphocytic leukemia (CLL patients is mostly characterized by immunosuppression, there is an accumulation of in vivo (graft-versus-leukemia effect and in vitro (spontaneous remissions after infections data that indicates that CLL might be effectively targeted by T-cell based immunotherapy. Recently, we characterized receptor for hyaluronic acid mediated motility (RHAMM as a preferential target for immunotherapy of CLL. We also completed a RHAMM-derived peptide vaccination phase I/II clinical trial in CLL. Here, we present a detailed immunological analysis of six CLL patients vaccinated with HLA-A2 restricted RHAMM-derived epitope R3 (ILSLELMKL. Beside effective induction of R3-specific cytotoxic T-cells, peptide vaccination caused profound changes in different T-cell subsets as well as cytokines. We present longitudinal analyses of Th17, CD8+CD103+, CD8+CD137+ and IL-17 producing CD8+ T cells (CD8+IL- -17+ as well as important cytokines involved in regulation of immune response such as TGF-β, IL-10, IL-2 and TNF throughout the peptide vaccination period. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 1, 161–167

  19. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  20. Effects of the Intelligent-Turtle Massage on the Physical Symptoms and Immune Functions in Patients with Chronic Fatigue Syndrome

    Institute of Scientific and Technical Information of China (English)

    WANG Ji-hong; CHAI Tie-qu; LIN Guo-hua; LUO Lin

    2009-01-01

    To evaluate the effects of the intelligent-turtle massage on the physical symptoms and immune functions in patients with chronic fatigue syndrome (CFS). Methods: 182 cases of CFS were randomly divided into an experimental group of 91 cases treated by the intelligent-turtle massage,and a control group of 91 cases treated with the conventional massage method. After 2 courses of treatment,the therapeutic effects were statistically analyzed with the accumulated score for the improved clinical symptoms; and the changes of IgA,IgM and IgG were compared in 96 cases. Results: There was a significant difference between the two groups in the accumulated scores for improvement of the symptoms (P<0.05). A remarkable difference was found in the therapeutic effect. And there was a significant difference in the IgA,IgM and IgG levels between the two groups (P<0.05). Conclusion: The intelligent-turtle massage is an effective therapy for relieving the physical symptoms of CFS,and it may show certain effects on the immune functions.

  1. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

    NARCIS (Netherlands)

    R.A.C. Hughes (Richard); P. Donofrio (Peter); V. Bril (Vera); M.C. Dalakas (Marinos); C. Deng (Chunqin); K. Hanna (Kim); H.P. Hartung; N. Latov (Norman); I.S.J. Merkies (Ingemar); P.A. van Doorn (Pieter)

    2008-01-01

    textabstractBackground: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune

  2. Effect of High Dose Dexamethasone on Function and TLR-9 mRNA Expression of Plasmacytoid Dendritic Cells in Patients with Immune Thrombocytopenic Purpura%大剂量地塞米松对免疫性血小板减少性紫癜患者浆细胞样树突状细胞功能及Toll样受体9mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    王莉; 张连生; 柴晔; 曾鹏云; 吴重阳

    2012-01-01

    本研究探讨大剂量地塞米松对免疫性血小板减少性紫癜(ITP)患者外周血浆细胞样树突状细胞(pDC)功能及Toll样受体9(TLR9)表达的影响.15例初诊的ITP患者给予地塞米松40 mg/d,连用4d,采用免疫磁珠分离法体外分离15例正常对照及13例治疗有效患者治疗前后外周血中pDC;用CpG-ODN 2216刺激外周血pDC并与之共培养24h,采用ELISA方法检测上清中IFN-α、IL-6、TNF-α的含量;用实时定量聚合酶链反应(RT-PCR)检测pDC的TLR9 mRNA表达量.结果表明,①治疗前pDC产生IFN-α、IL-6、TNF-α水平[(960.83±164.65)pg/ml,(156.15±39.89)pg/ml,(137.31±35.44) pg/ml)]明显高于正常对照组[(616.67±105.98) pg/ml,(89.13±21.48) pg/ml,(88.53±25.81) pg/ml,P<0.05];治疗后pDC产生IFN-α、IL-6、TNF-α水平分别降至(678.46±128.88) pg/ml,(97.77±26.31) pg/ml,(103.08±26.42) pg/ml,与治疗前比较差异有统计学意(P<0.05),与正常对照组相比差异无统计学意义(P>0.05);②治疗前pDC的TLR9 mRNA的表达水平高于正常对照组(P<0.05);治疗后pDC的TLR9 mRNA的表达水平低于治疗前(P<0.05),与正常对照组比较差异无统计学显著性(P>0.05).结论:pDC分泌的细胞因子及其表达的TLR9在ITP发病中起重要作用;地塞米松可能通过下调TLR9的表达,抑制pDC分泌细胞因子的功能,而对ITP起到治疗作用.%This study was purposed to investigate the effect of high-dose dexamethasone ( DXM) on function and Toll like receptor 9 (TLR-9) expression of plasmacytoid dendritic cells ( pDC) in peripheral blood of patients with immune thrombocytopenic purpura( ITP). 15 newly diagnosed patients with ITP received high dose DXM at single daily doses of 40 mg for 4 consecutive days. The peripheral blood plasmacytoid dendritic cells from 13 remission patients and 15 nor-mal controls were separated by immunomagnetie beads and then induced by CpG-OND2216. 24 h later, the levels of IFN-α,IL-6 and TNF-α in the

  3. Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    Erdal Kurtoglu; Ertugrul Kayacetin; Aysegul Ugur

    2004-01-01

    AIM: To compare the prevalence of Helicobacter pylori (Hpylori) infection in autoimmune thrombocytopenic purpura (AITP) patients with that of nonthrombocytopenic controls,and to evaluate the efficacy of the treatment in H pylori(+)and H pylori(-) AITP patients.METHODS: The prevalence of gastric H pylori infection in 38 adult AITP patients (29 female and 9 male; median age 27 years; range 18-39 years) who consecutively admitted to our clinic was investagated.RESULTS: H pylori infection was found in 26 of 38 AITP patients (68.5%). H pylori infection was found in 15 of 23control subjects (65.2%). The difference in H pylori infection between the 2 groups was not significant. Thrombocyte count of H pylori-positive AITP patients was significantly lower than that of H pylori-negative AITP patients (P<0.05).Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group (P<0.05).CONCLUSION: H pylori infection should be considerecd in the treatment of AITP patients with H pylori infection.

  4. Influence of the invasion of peripheral blood mononuclear cells by hepatitis B virus on immune response of the patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    XING Tong-jing; ZHANG Lian; HOU Jin-lin; ZHANG Ming-xia; YANG Jie; LUO Kang-xian

    2001-01-01

    To explore the influence of HBV invasion into peripheral blood mononuclear cells (PBMC) on the immune response of patients with chronic hepatitis B. Methods: The cytokine levels in the culture supernatant of PBMC from 56 patients with chronic hepatitis B were determined by ELISA, and PCR was employed to amplify the HBV DNA. Results: The levels of IFN-γ in patients with hepatitis B was lower than thoset of the control, but the difference was not statistically significant, while the levels of IL-4 were significantly higher than those of the control (P<0.01). The serum levels of HBV DNA were negatively correlated with that of IFN-y in culture supernatants of PBMC. Thirty-five patients positive of HBV DNA in the PBMCs were identified from 56 patients with hepatitis B,and their IFN-γ level proved to be significantly different. Conclusions: Th2 cell-mediated immune response is predominant in chronic hepatitis B which is associated with the chronicity of HBV infection. HBV invasion into the PBMCs may affect Th1 and Th2 cell-mediated immune response of the patients with chronic hepatitis B.

  5. Is MS an auto-immune disease or a chronic gammaherpesvirus infection?

    Science.gov (United States)

    MacGregor, H S; Latiwonk, Q I

    1996-01-01

    The geographical-epidemiological findings of MS over the past 75 years are reviewed. Evidence concerning PR latitude-gradients, clusters, migration patterns, and enhancement-protective factors are critically reviewed and analyzed. The evidence in genetics, twin-studies and auto-immune theories are also thoroughly scrutinized as to their possible involvement as causative factors in MS- and found to be somewhat lacking. Environmental discoveries in the Faroes and Key West clusters are reviewed for possible similar environmental causes by a deadly agent. Exogenous-environmental candidate agents over the past 35 years from measles to Marek's are reviewed and analyzed. The undisputed positive laboratory findings of MDV are discussed in relation to Bray's unusually high positive findings with EBV antigen and MS serums. The important discovery of HHV-6 in oligodendrocytes of MS brains but not controls is considered and how this might relate to MDV. The conclusion is that genetics are indeed important in the natural resistance of individual immune systems to invading infectious agents (especially herpesviruses) but genetics in general have little to do with the pathogenesis of multiple sclerosis (but HHV-6, EBV, and MDV do).

  6. Within-host co-evolution of chronic viruses and the adaptive immune system

    Science.gov (United States)

    Nourmohammad, Armita

    We normally think of evolution occurring in a population of organisms, in response to their external environment. Rapid evolution of cellular populations also occurs within our bodies, as the adaptive immune system works to eliminate infection. Some pathogens, such as HIV, are able to persist in a host for extended periods of time, during which they also evolve to evade the immune response. In this talk I will introduce an analytical framework for the rapid co-evolution of B-cell and viral populations, based on the molecular interactions between them. Since the co-evolution of antibodies and viruses is perpetually out of equilibrium, I will show how to quantify the amount of adaptation in each of the two populations by analysis of their co-evolutionary history. I will discuss the consequences of competition between lineages of antibodies, and characterize the fate of a given lineage dependent on the state of the antibody and viral populations. In particular, I will discuss the conditions for emergence of highly potent broadly neutralizing antibodies, which are now recognized as critical for designing an effective vaccine against HIV.

  7. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura.

    Science.gov (United States)

    Hou, Ming; Peng, Jun; Shi, Yan; Zhang, Chunqing; Qin, Ping; Zhao, Chuanli; Ji, Xuebin; Wang, Xueyong; Zhang, Maohong

    2003-06-01

    The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

  8. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema.

    Directory of Open Access Journals (Sweden)

    Sandra Grumelli

    2004-10-01

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells, but not CCR3 or CCR4 (markers of T helper 2 cells. Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12, a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.

  9. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    Science.gov (United States)

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas.

  10. Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection.

    Science.gov (United States)

    Kran, Anne-Marte B; Sommerfelt, Maja A; Baksaas, Ingebjørg; Sørensen, Birger; Kvale, Dag

    2012-03-01

    Therapeutic immunization in chronic HIV infection aims to induce durable, HIV-specific immune responses capable of controlling disease progression, but immunological correlates of clinical efficacy are poorly defined. We have previously immunized 38 patients with a mixture of four short Gag p24-like conserved peptides (Vacc-4x) targeting skin dendritic cells. Antiretroviral treatment (ART) was initially stopped after completed immunizations and resumed post-protocol during regular clinical follow-up according to current guidelines. Four years after enrolment, Vacc-4x-specific cellular responses were evaluated in vivo by delayed-type hypersensitivity (DTH) skin test, and in vitro by a T-cell proliferation assay. Kaplan-Meier product-limit estimates were used to analyse time until ART was resumed. Peptide-specific cellular immune responses induced by Vacc-4x had persisted 4 years after the last immunization in terms of unchanged DTH independent of ART and detectable proliferative T-cell responses which correlated to the native peptides (R = 0.73, p = 0.01). Circulating bifunctional (IFN-γ and IL-10) Vacc-4x-specific T-cell clones were detected in 43% of patients. Subjects with the strongest post-immunization DTH responses appeared to start ART later compared with DTH low responders (p = 0.07). These data suggest that DTH responses should be further evaluated as a new and convenient tool for predicting clinical efficacy in trials testing therapeutic immunizations.

  11. Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

    Science.gov (United States)

    Picat, Marie-Quitterie; Pellegrin, Isabelle; Bitard, Juliette; Wittkop, Linda; Proust-Lima, Cécile; Liquet, Benoît; Moreau, Jean-François; Bonnet, Fabrice; Blanco, Patrick; Thiébaut, Rodolphe

    2017-01-01

    Objectives To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. Design Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. Methods Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM). Results The main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect

  12. Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report.

    Science.gov (United States)

    Georgiades, F; Demosthenous, S; Braimi, M; Tsitskari, T; Psarelis, S

    2015-11-01

    Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up.

  13. DNMT3B 579G>T promoter polymorphism and the risk for idiopathic thrombocytopenic purpura in a Chinese population.

    Science.gov (United States)

    Zhao, Haifeng; Du, Weiting; Gu, Dongsheng; Wang, Donghai; Xue, Feng; Ge, Jing; Sui, Tao; Yang, Renchi

    2009-01-01

    Epigenetics may influence the expression of numerous genes, which might contribute to autoimmune diseases. DNA methylation is mediated by DNA methyltransferases, especially DNA methyltransferase 3B (DNMT3B). Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between DNMT3B 579G>T and the risk for idiopathic thrombocytopenic purpura (ITP). The DNMT3B 579G>T polymorphisms were analyzed by PCR-RFLP. There was no significant difference in genotype and allele distribution between the ITP patient and the controls (p = 0.722 and 0.667, respectively). Similar results were observed between the 2 groups when stratified by age and disease course, including acute in childhood, chronic in childhood, acute in adult and chronic in adult. Importantly, this study showed a statistical difference in the distribution of SNP of DNMT3B between Chinese and Koreans or Americans. It is shown that the SNP of DNMT3B 579G>T may not be used on its own as a marker to predict the susceptibility to ITP in a Chinese population and that DNMT3B 579G>T promoter SNP varies from one ethnic population to another.

  14. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

    Directory of Open Access Journals (Sweden)

    D. J. Kuter

    2014-01-01

    Full Text Available Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP. This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis, platelet response (platelet count >50 × 109 per litre, and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

  15. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

    Directory of Open Access Journals (Sweden)

    D. J. Kuter

    2015-01-01

    Full Text Available Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP. This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis, platelet response (platelet count >50 × 109 per litre, and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

  16. Th17/IL-17A might play a protective role in chronic lymphocytic leukemia immunity.

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    Iwona Hus

    Full Text Available Th17 cells, a recently discovered subset of T helper cells that secrete IL-17A, can affect the inflammation process autoimmune and cancer diseases development. The purpose of this study was to evaluate the role of Th17 cells and IL17A in biology of CLL. The study group included 294 untreated CLL patients in different clinical stages. Here, we show that higher Th17 and IL-17A values were associated with less advanced clinical stage of CLL. Th17 cells' percentages in PB were lower in patients who died due to CLL during follow-up due to CLL (as compared to surviving patients and in patients responding to first-line therapy with fludarabine-based regimens (as compared to non-responders. IL-17A inversely correlated with the time from CLL diagnosis to the start of therapy and was lower in patients who required treatment during follow-up. Th-17 and IL-17A values were lower in patients with adverse prognostic factors (17p and 11q deletion, CD38 and ZAP-70 expression. CLL patients with detectable IL-17A mRNA in T cells were in Rai Stage 0 and negative for both ZAP-70 and CD38 expression. Th17 percentages positively correlated with iNKT and adversely with Treg cells. The results of this study suggest that Th17 may play a beneficial role in CLL immunity.

  17. Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report

    Institute of Scientific and Technical Information of China (English)

    Xiao-Peng Qu; Zhen-Xiao Huang; Yan Sun; Ting Ye; Shun-Jiu Cui; Qian Huang; Li-Jing Ma

    2015-01-01

    Background:Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS),but its role in the inflammatory process of pCRS is unclear.It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS),including antimicrobial peptides and pattern recognition receptors (PRRs).The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS.Methods:Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study.Adenoidal epithelium was isolated,and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS:Human β-defensin (HBD) 2 and 3,surfactant protein (SP)-A and D,toll-like receptors 1-10,nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1,NOD 2,and NACHT,LRR and PYD domains-containing protein 3,retinoic acid-induced gene 1,melanoma differentiation-associated gene 5,and nuclear factor-KB (NF-κB).RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests.Results:The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs.AH 1.21 ± 0.15;P =0.0173,t =2.654).The relative expression levels of all tested PRRs and NF-κB,as well as HBD-2,HBD-3,and SP-A,showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group.Conclusions:Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS.PRRs,however,are unlikely to play a significant role in the inflammatory process of pCRS.

  18. Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Qu

    2015-01-01

    Full Text Available Background: Adenoid hypertrophy (AH is associated with pediatric chronic rhinosinusitis (pCRS, but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS, including antimicrobial peptides and pattern recognition receptors (PRRs. The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. Methods: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human β-defensin (HBD 2 and 3, surfactant protein (SP-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain (NOD-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-κB (NF-κB. RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. Results: The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ± 0.15; P = 0.0173, t = 2.654. The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. Conclusions: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process of pCRS.

  19. Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis

    Science.gov (United States)

    Elvington, M; Schepp-Berglind, J; Tomlinson, S

    2015-01-01

    The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB–/– mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD. PMID:25293413

  20. AIM2 co-immunization favors specific multifunctional CD8(+) T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis.

    Science.gov (United States)

    Chai, Dafei; Yue, Yan; Xu, Wei; Dong, Chunsheng; Xiong, Sidong

    2015-07-01

    Coxsackievirus B3 (CVB3) infection can cause acute myocarditis and chronic myocarditis, leading to dilated cardiomyopathy (DCM) with no effective therapeutic strategy. Therefore, we investigated the potential of absent in melanoma 2 (AIM2) to enhance the therapeutic efficacy of DNA vaccine against CVB3-induced chronic myocarditis. Mice were infected with CVB3 and then intranasally immunized with chitosan-pcDNA3.1 (mock), chitosan-pAIM2 (CS-pAIM2), chitosan-pVP1 (CS-pVP1), or chitosan-pAIM2 plus chitosan-pVP1 (CS-pAIM2/CS-pVP1) at 7, 21, and 35d. Therapeutic efficacies of various vaccines were evaluated at day 56d. Compared with CS-pVP1 immunization, CS-pAIM2/CS-pVP1 co-immunization significantly increased survival rate, improved cardiac function, as well as decreased myocardial injury and fibrosis, this result indicated that CVB3-induced chronic myocarditis was alleviated. CVB3-specific T lymphocyte proliferation and cytotoxic T lymphocyte responses of the CS-pAIM2/CS-pVP1 co-immunization group were also increased. More interestingly, CS-pAIM2/CS-pVP1 co-immunization could facilitate CVB3-specific multifunctional CD8(+) T cell induction in the intestinal mucosa, and this induction was closely correlated with myocardial scores, this result indicated that CS-pAIM2/CS-pVP1 vaccine exhibits therapeutic efficacy by enhancing multifunctional CD8(+) T cells. This study may represent a novel therapy for CVB3-induced chronic myocarditis.

  1. Treatment of 36 cases of thrombotic thrombocytopenic purpura

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    Suvajdžić-Vuković Nada D.

    2004-01-01

    Full Text Available Thirty-six patients (pts. with thrombotic thrombocytopenic purpura (TTP were treated between May 1990 and May 2003. There were 31 women and 5 men; the average age was 37 years. Twenty-five cases were idiopathic and 11 secondary (3 infection - related, 5 occurred during pregnancy and 3 were drug - associated. The mean lag period between the first symptoms and the diagnosis was 8.5 days (in 14 pts. £ 5; in 22 > 5. On diagnosis neurological symptoms were present in 31, bleeding in 33, fever in 21 and renal impairment in 27 patients. The mean hemoglobin was 67.5 g/L, the mean platelet count was 10´109/L, and the mean reticulocytosis was 17%. The mean serum LDH was 1457 IU. Treatment included plasma exchange (PE in 24 pts. and only plasma infusions in 12 pts. There were 24 complete responders (20 on PE and 12 deaths (4 on PE; PE significantly improved survival (p<0.01. There were 5 treatment-related complications due to the infection and bleeding, 17 exacerbations and 4 relapses. The mean time delay before the onset of symptoms and the treatment initiation lasted for 9 days suggesting the poor disease recognition; the mean time delay from diagnosis to PE institution was 6 days, indicating postponed PE. The mean treatment duration in all patients was 18 days; the mean number of PE cycles needed for the platelet count stabilization was 9. Good prognostic indicators of survival were: the longer prodromal period (>5 days, the secondary form of TTP and the absence of coma at presentation. The use of PE significantly improved survival. TTP is a severe disorder requiring early recognition and diagnosis in general medical care facilities, which should lead to the timely treatment with PE.

  2. Effects of in vivo chronic hydrocarbons pollution on sanitary status and immune system in sea bass (Dicentrarchus labrax L.).

    Science.gov (United States)

    Danion, Morgane; Le Floch, Stéphane; Kanan, Rami; Lamour, François; Quentel, Claire

    2011-10-01

    Following the development of an experimental system to expose adult fish to low and stable concentration of pollutant over a prolonged period, the in vivo effects of hydrocarbons on sanitary status, i.e. the health status of fish with regard to chemical pollution, and immune system in sea bass, Dicentrarchus labrax were assessed. A total of 90 fish were acclimated for 15 days, then 45 fish were exposed to the water soluble fraction (WSF) of Arabian crude oil, similar to a complex pollution by hydrocarbons chronically observed in situ in estuaries, while the 45 other control fish sustained the same experimental conditions in clean seawater. After 21 days of exposure, 30 contaminated and control fish were sampled, then 30 other fish were collected after a 15 day recovery period in clean sea water. PAH concentrations in crude oil, WSF, muscles and bile were measured by gas chromatography coupled with mass spectrometry analysis. White blood cell counts and differential leucocyte counts were determined by classical haematology methods. Cell mortality and phagocytosis activity of leucocytes were analyzed by flow cytometry. Haemolytic alternative complement activity and stress parameters were analyzed in blood plasma by spectrophotometry. After a 21 day exposure period to a mixture of 41 parent/alkylated-PAHs (835 ± 52/85 ± 1 5 ng L(-1)). Fish flesh was contaminated by a bioconcentration of naphthalene very closed to the Reference Dose for Oral Exposure estimated by US-EPA's Integrated Risk Information System, causing a potential risk for human consumers. A leucopenia due to a lymphopenia, a rise in leucocyte mortality and a decrease in phagocytosis activity were noted in contaminated fish compared to controls. All these results may be explained by the damage to membrane cells integrity by uptake of PAHs and suggested an impairment of specific and nonspecific immune systems. After a 15 day recovery period, effects were reversible for sanitary status and an offset in

  3. Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.

    Science.gov (United States)

    Rozera, G; Abbate, I; Vlassi, C; Giombini, E; Lionetti, R; Selleri, M; Zaccaro, P; Bartolini, B; Corpolongo, A; D'Offizi, G; Baiocchini, A; Del Nonno, F; Ippolito, G; Capobianchi, M R

    2014-03-01

    HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.

  4. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

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    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  5. Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

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    Peter Kraft

    2015-10-01

    Full Text Available Immune cells (IC play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA, chronic cerebrovascular disease (CCD and healthy volunteers (HV. We conducted a case-control study of patients with AIS/TIA (n = 116 or CCD (n = 117, and HV (n = 104 who were enrolled at the University Hospital Würzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.

  6. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

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    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  7. Immune regulation of a chronic bacteria infection and consequences for pathogen transmission

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    Pathak Ashutosh K

    2010-08-01

    Full Text Available Abstract Background The role of host immunity has been recognized as not only playing a fundamental role in the interaction between the host and pathogen but also in influencing host infectiousness and the ability to shed pathogens. Despite the interest in this area of study, and the development of theoretical work on the immuno-epidemiology of infections, little is known about the immunological processes that influence pathogen shedding patterns. Results We used the respiratory bacterium Bordetella bronchiseptica and its common natural host, the rabbit, to examine the intensity and duration of oro-nasal bacteria shedding in relation to changes in the level of serum antibodies, blood cells, cytokine expression and number of bacteria colonies in the respiratory tract. Findings show that infected rabbits shed B. bronchiseptica by contact up to 4.5 months post infection. Shedding was positively affected by number of bacteria in the nasal cavity (CFU/g but negatively influenced by serum IgG, which also contributed to the initial reduction of bacteria in the nasal cavity. Three main patterns of shedding were identified: i- bacteria were shed intermittently (46% of individuals, ii- bacteria shedding fell with the progression of the infection (31% and iii- individuals never shed bacteria despite being infected (23%. Differences in the initial number of bacteria shed between the first two groups were associated with differences in the level of serum antibodies and white blood cells. These results suggest that the immunological conditions at the early stage of the infection may play a role in modulating the long term dynamics of B. bronchiseptica shedding. Conclusions We propose that IgG influences the threshold of bacteria in the oro-nasal cavity which then affects the intensity and duration of individual shedding. In addition, we suggest that a threshold level of infection is required for shedding, below this value individuals never shed bacteria

  8. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nybo, Mads

    2014-01-01

    in thrombocytopenia. Flow cytometry, platelet aggregometry and platelet secretion tests are used to diagnose specific platelet function defects. The flow cytometric activation marker P-selectin and surface coverage by the Cone and Plate[let] analyser™ predict bleeding in selected thrombocytopenic populations...

  9. Refractory thrombotic thrombocytopenic purpura in a 16-year-old girl: successful treatment with bortezomib

    NARCIS (Netherlands)

    Balen, T. van; Schreuder, M.F.; Jong, H. de; Kar, N.C.A.J. van de

    2014-01-01

    We present a case of a 16-year-old girl with autoimmune thrombotic thrombocytopenic purpura (TTP), refractory to plasma exchange and high-dose prednisone. Despite the additional treatment with rituximab, she developed renal and neurological complications with ongoing hemolysis and thrombocytopenia.

  10. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders.

    NARCIS (Netherlands)

    Besbas, N.; Karpman, D.; Landau, D.; Loirat, C.; Proesmans, W.; Remuzzi, G.; Rizzoni, G.; Taylor, C.M.; Kar, N.C.A.J. van de; Zimmerhackl, L.B.

    2006-01-01

    The diagnostic terms hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are based on historical and overlapping clinical descriptions. Advances in understanding some of the causes of the syndrome now permit many patients to be classified according to etiology. The increase

  11. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

    OpenAIRE

    Hughes, Richard; Donofrio, Peter; Bril, Vera; Dalakas, Marinos; Deng, Chunqin; Hanna, Kim; Hartung, H P; Latov, Norman; Merkies, Ingemar; van Doorn, Pieter

    2008-01-01

    textabstractBackground: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treat...

  12. Effect of Protein Kinase C on Proliferation and Apoptosis of T Lymphocytes in Idiopathic Thrombocytopenic Purpura Children

    Institute of Scientific and Technical Information of China (English)

    Changlin Wu; Fang Liu; Xuemin Zhou; Zhengwei Cheng; Xiaomeng Yang; Hong Xiao; Qun Chen; Kangrong Cai

    2005-01-01

    It is well-documented that T lymphocyte proliferation and apoptosis are abnormal in idiopathic thrombocytopenic purpura (ITP) children. However, the underlying regulation mechanisms especially in terms of signal transduction remain unknown. In this paper, we reported the changes of protein kinase C (PKC) activity in peripheral blood T lymphocytes and the effect of PKC on T lymphocyte proliferation and apoptosis. We demonstrated that in ITP children, the activator (PMA) and inhibitor (H-7) of PKC affected on T lymphocyte proliferation and apoptosis dramatically, but they altered little in healthy children. PKC activity was significantly enhanced in ITP children together with an increased expression of FasL on CD3+ T, CD4+ T and CD8+T cells, resulting in a positive correlation between PKC activity and the expression of FasL on T cells. While the PKC activity and the platelet count were negatively correlated. Taken together, our findings suggest that the PKC activation may enhance T lymphocytes activity, suppress T cell apoptosis and be involve in thrombocytes damage as a mechanism related to immune pathogenesis of ITP.

  13. Clinical significance of variations in levels of Epstein-Barr Virus (EBV) antigen and adaptive immune response during chronic active EBV infection in children.

    Science.gov (United States)

    Xing, Yan; Song, Hong Mei; Wei, Min; Liu, Yu; Zhang, Yu Hua; Gao, Li

    2013-01-01

    Pediatric patients were recruited to analyze differences in Epstein-Barr virus (EBV) copy numbers and adaptive immune reactions in children with chronic active vs acute EBV infection (CAEBVI vs AEBVI), as well as to examine the relationship between these parameters and the pathogenesis of CAEBVI. Fluorescent qPCR was used to assess EBV-DNA levels, while ELISA, antibody affinity, flow cytometry, and heterophil agglutination (HA) assays were used to evaluate patient EBV-adaptive humoral and cellular immunity. Lastly, ELISPOT was employed to assess interferon (IFN)-γ secretory functions of EBV-specific cytotoxic T-lymphocytes (CTL) as a marker of subject EBV-specific adaptive cellular immunity. The results indicated that, compared with AEBVI patients or normal children, there was a dramatic elevation in viral copy levels, viral capsid antigen (VCA)-IgA, early antigen (EA)-IgA, and EA-IgG, but a lack of EBV nuclear antigen (EBNA)-IgG and a negative HA in CAEBVI patients (p EBV-specific CTL function compared with normal children (p EBV antigen availability and in both the adaptive humoral and cellular immune responses in patients with CAEBVI, and that these outcomes may be associated with the chronic active re-infection process itself associated with CAEBVI.

  14. Chronic Ingestion of Coal Fly-Ash Contaminated Prey and Its Effects on Health and Immune Parameters in Juvenile American Alligators (Alligator mississippiensis).

    Science.gov (United States)

    Finger, John W; Hamilton, Matthew T; Metts, Brian S; Glenn, Travis C; Tuberville, Tracey D

    2016-10-01

    Coal-burning power plants supply approximately 37 % of the electricity in the United States. However, incomplete combustion produces ash wastes enriched with toxic trace elements that have historically been disposed of in aquatic basins. Organisms inhabiting such habitats may accumulate these trace elements; however, studies investigating the effects on biota have been primarily restricted to shorter-lived, lower-trophic organisms. The American alligator (Alligator mississippiensis), a long-lived, top-trophic carnivore, has been observed inhabiting these basins, yet the health or immune effects of chronic exposure and possible accumulation remains unknown. In this study, we investigated how chronic dietary ingestion of prey contaminated with coal combustion wastes (CCWs) for 25 months, and subsequent accumulation of trace elements present in CCWs, affected juvenile alligator immune function and health. Alligators were assigned to one of four dietary-treatment groups including controls and those fed prey contaminated with CCWs for one, two, or three times a week. However, no effect of Dietary Treatment (p > 0.05) was observed on any immune parameter or hematological or plasma analyte we tested. Our results suggest that neither exposure to nor accumulation of low doses of CCWs had a negative effect on certain aspects of the immune and hematological system. However, future studies are required to elucidate this further.

  15. Monocytes expand with immune dysregulation and is associated with insulin resistance in older individuals with chronic HIV.

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    Cecilia M Shikuma

    Full Text Available Rates of insulin resistance are increased in HIV-infected patients on stable antiretroviral therapy (ART. Such increase may partially be due to HIV-induced immune dysregulation involving monocytes (MO and its subsets.Cross-sectional analysis of 141 HIV-infected subjects age ≥ 40 years on stable ART. Homeostatic model assessment-insulin resistance (HOMA-IR and rates of metabolic syndrome were calculated. Subjects were classified by fasting glucose and oral glucose tolerance test (OGTT into clinical diabetes categories. Multi-parametric flow cytometry was used to determine MO subset percentages: [classical (CD14(++CD16(-, intermediate (CD14(++CD16(+, non-classical (CD14(low/+CD16(++, and a recently identified fourth (CD14(low/+CD16(- 'transitional' MO subset] and percentage of activated (CD38(+HLA-DR(+ CD8 T cells. Absolute levels of cells were calculated using clinical CBC and T cell subset data. Multiple plasma soluble biomarkers were assessed by Luminex technology.Median age 50 years, CD4 count (percent 505 cells/µL (29%, and 89% male. Total MO (r=-0.23, p=0.006 and classical and non-classical MO subsets correlated negatively with CD4 percent. No correlations were seen with CD4 count as absolute values. Log-total MO and log-classical MO predicted HOMA-IR independently of HIV immuno-virologic and diabetes risk factors (β=0.42, p=0.02 and β=0.35, p=0.02, respectively and were increased in subjects with metabolic syndrome (p=0.03 and p=0.05 respectively. Total and/or subset MO levels correlated with multiple soluble plasma biomarkers including CRP, IL-6, MMP-9, MPO, SAA, SAP and tPAI-1, with tPAI-1 independently predicting HOMA-IR (β=0.74, p<0.001.MO levels increase with worsening HIV immune dysregulation as assessed by CD4 percent. CD4 percent may provide additional information about MO and metabolic risk in this population beyond absolute values. MO, and specifically classical MO, may contribute to insulin resistance and metabolic syndrome

  16. Splenectomy in children with idiopathic thrombocytopenic purpura : A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

    NARCIS (Netherlands)

    Kuehne, Thomas; Blanchette, Victor; Buchanan, George R.; Ramenghi, Ugo; Donato, Hugo; Tamminga, Rienk Y. J.; Rischewski, Johannes; Berchtold, Willi; Imbach, Paul

    2007-01-01

    Background. Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. Procedure. Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in

  17. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura

    NARCIS (Netherlands)

    Houwerzijl, EJ; Blom, NR; van der Want, JJL; Esselink, MT; Koornstra, JJ; Smit, JW; Louwes, H; Vellenga, E; de Wolf, JTM

    2004-01-01

    To investigate whether altered megakaryocyte morphology contributes to reduced platelet production in idiopathic thrombocytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was performed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apoptosis were present in

  18. Immune and viral correlates of "secondary viral control" after treatment interruption in chronically HIV-1 infected patients.

    Directory of Open Access Journals (Sweden)

    Ellen Van Gulck

    Full Text Available Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC, were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of

  19. The Gut-Liver-Lung Axis. Modulation of the Innate Immune Response and Its Possible Role in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Young, Robert P; Hopkins, Raewyn J; Marsland, Benjamin

    2016-02-01

    Evidence from epidemiological studies suggests that a diet high in fiber is associated with better lung function and reduced risk of chronic obstructive pulmonary disease (COPD). The mechanism for this benefit remains unknown, but, as fiber is not absorbed by the gut, this finding suggests that the gut may play an active role in pathogenic pathways underlying COPD. There is a growing awareness that aberrant activity of the innate immune system, characterized by increased neutrophil and macrophage activation, may contribute to the development or progression of COPD. Innate immunity is modulated in large part by the liver, where hepatic cells function in immune surveillance of the portal circulation, as well as providing a rich source of systemic inflammatory cytokines and immune mediators (notably, IL-6 and C-reactive protein). We believe that the beneficial effect of dietary fiber on lung function is through modulation of innate immunity and subsequent attenuation of the pulmonary response to inflammatory stimuli, most apparent in current or former smokers. We propose that the "gut-liver-lung axis" may play a modifying role in the pathogenesis of COPD. In this review, we summarize lines of evidence that include animal models, large prospective observational studies, and clinical trials, supporting the hypothesis that the gut-liver-lung axis plays an integral part in the pathogenic mechanisms underlying the pathogenesis of COPD.

  20. Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

    Directory of Open Access Journals (Sweden)

    Abdelsadik Ahmed

    2010-04-01

    response is highly tissue-specific. Our analysis indicates that chronic activation of the salivary gland's immune system is costly, as it induces severe reduction in growth throughout development. The IMD-regulated increase in expression levels of the fly's presenilin representatives opens the opportunity to use the salivary glands for studying the physiological and pathophysiological role of these genes in a simple but functional environment.

  1. The Use of Feed Additives to Reduce the Effects of Aflatoxin and Deoxynivalenol on Pig Growth, Organ Health and Immune Status during Chronic Exposure

    Directory of Open Access Journals (Sweden)

    Sung Woo Kim

    2013-07-01

    Full Text Available Three feed additives were tested to improve the growth and health of pigs chronically challenged with aflatoxin (AF and deoxynivalenol (DON. Gilts (n = 225, 8.8 ± 0.4 kg were allotted to five treatments: CON (uncontaminated control; MT (contaminated with 150 µg/kg AF and 1100 µg/kg DON; A (MT + a clay additive; B (MT + a clay and dried yeast additive; and C (MT + a clay and yeast culture additive. Average daily gain (ADG and feed intake (ADFI were recorded for 42 days, blood collected for immune analysis and tissue samples to measure damage. Feeding mycotoxins tended to decrease ADG and altered the immune system through a tendency to increase monocytes and immunoglobulins. Mycotoxins caused tissue damage in the form of liver bile ductule hyperplasia and karyomegaly. The additives in diets A and B reduced mycotoxin effects on the immune system and the liver and showed some ability to improve growth. The diet C additive played a role in reducing liver damage. Collectively, we conclude that AF and DON can be harmful to the growth and health of pigs consuming mycotoxins chronically. The selected feed additives improved pig health and may play a role in pig growth.

  2. The use of feed additives to reduce the effects of aflatoxin and deoxynivalenol on pig growth, organ health and immune status during chronic exposure.

    Science.gov (United States)

    Weaver, Alexandra C; See, M Todd; Hansen, Jeff A; Kim, Yong B; De Souza, Anna L P; Middleton, Teena F; Kim, Sung Woo

    2013-07-01

    Three feed additives were tested to improve the growth and health of pigs chronically challenged with aflatoxin (AF) and deoxynivalenol (DON). Gilts (n = 225, 8.8 ± 0.4 kg) were allotted to five treatments: CON (uncontaminated control); MT (contaminated with 150 µg/kg AF and 1100 µg/kg DON); A (MT + a clay additive); B (MT + a clay and dried yeast additive); and C (MT + a clay and yeast culture additive). Average daily gain (ADG) and feed intake (ADFI) were recorded for 42 days, blood collected for immune analysis and tissue samples to measure damage. Feeding mycotoxins tended to decrease ADG and altered the immune system through a tendency to increase monocytes and immunoglobulins. Mycotoxins caused tissue damage in the form of liver bile ductule hyperplasia and karyomegaly. The additives in diets A and B reduced mycotoxin effects on the immune system and the liver and showed some ability to improve growth. The diet C additive played a role in reducing liver damage. Collectively, we conclude that AF and DON can be harmful to the growth and health of pigs consuming mycotoxins chronically. The selected feed additives improved pig health and may play a role in pig growth.

  3. Seroprevalence of chronic hepatitis B virus infection and prior immunity in immigrants and refugees: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Carmine Rossi

    Full Text Available BACKGROUND: International migrants experience increased mortality from hepatocellular carcinoma compared to host populations, largely due to undetected chronic hepatitis B infection (HBV. We conducted a systematic review of the seroprevalence of chronic HBV and prior immunity in migrants arriving in low HBV prevalence countries to identify those at highest risk in order to guide disease prevention and control strategies. METHODS AND FINDINGS: Medline, Medline In-Process, EMBASE and the Cochrane Database of Systematic Reviews were searched. Studies that reported HBV surface antigen or surface antibodies in migrants were included. The seroprevalence of chronic HBV and prior immunity were pooled by region of origin and immigrant class, using a random-effects model. A random-effects logistic regression was performed to explore heterogeneity. The number of chronically infected migrants in each immigrant-receiving country was estimated using the pooled HBV seroprevalences and country-specific census data. A total of 110 studies, representing 209,822 immigrants and refugees were included. The overall pooled seroprevalence of infection was 7.2% (95% CI: 6.3%-8.2% and the seroprevalence of prior immunity was 39.7% (95% CI: 35.7%-43.9%. HBV seroprevalence differed significantly by region of origin. Migrants from East Asia and Sub-Saharan Africa were at highest risk and migrants from Eastern Europe were at an intermediate risk of infection. Region of origin, refugee status and decade of study were independently associated with infection in the adjusted random-effects logistic model. Almost 3.5 million migrants (95% CI: 2.8-4.5 million are estimated to be chronically infected with HBV. CONCLUSIONS: The seroprevalence of chronic HBV infection is high in migrants from most world regions, particularly among those from East Asia, Sub-Saharan Africa and Eastern Europe, and more than 50% were found to be susceptible to HBV. Targeted screening and vaccination of

  4. Thrombotic thrombocytopenic purpura: MRI demonstration of persistent small cerebral infarcts after clinical recovery

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, O.; Cramon, D.Y. von [Day-Care Clinic for Cognitive Neurology, University of Leipzig (Germany); Max Planck Institute of Cognitive Neuroscience, Leipzig (Germany); Wittig, I. [Day-Care Clinic for Cognitive Neurology, University of Leipzig (Germany); Wiggins, C.J. [Max Planck Institute of Cognitive Neuroscience, Leipzig (Germany)

    2000-08-01

    Abnormalities in the brain of patients with thrombotic thrombocytopenic purpura (TTP) are infrequent on MRI, often reversible and mainly limited to symptomatic stages of the disease. We report a case in which high-resolution MRI demonstrated multiple persistent small cortical infarcts after clinical remission. High-resolution MRI investigations may detect clinically latent but permanent brain damage, and complement clinical judgement in guiding therapeutic decisions. (orig.)

  5. Cellular immune function change and chronic obstructive pulmonary disease%细胞免疫功能变化与慢性阻塞性肺疾病

    Institute of Scientific and Technical Information of China (English)

    姜素丽; 李亚; 李建生

    2012-01-01

    目前研究显示机体的免疫功能降低或紊乱在慢性阻塞性肺疾病的发生、发展过程中起着重要作用,执行非特异性免疫的细胞主要包括巨噬细胞、中性粒细胞、自然杀伤细胞、树突状细胞等,特异性免疫主要有T细胞和B细胞介导.参与免疫功能的细胞与慢性阻塞性肺疾病发生发展密切相关.%The current study shows that the body's immune function or disorders play an important role in the development and progression of chronic obstructive pulmonary disease (COPD).In which the non-specific immune cells include alveolar macrophage,polymorphonuclear,natural killer cells,dendritic cell,while the specific immunity are mediated by T lymphocytes and B lymphocyte cells. The cells involved in immune function are closely related with the development of COPD.

  6. Evidence-based mini-review: Is indium-labeled autologous platelet scanning predictive of response to splenectomy in patients with chronic immune thrombocytopenia?

    Science.gov (United States)

    Cuker, Adam; Cines, Douglas B

    2010-01-01

    Clinical scenario: An otherwise healthy 25-year-old woman returns to your office for management of chronic primary immune thrombocytopenia. She was diagnosed 6 months earlier and continues to require prednisone 15 mg daily and periodic infusions of intravenous immunoglobulin to maintain a hemostatic platelet count. You discuss second-line treatment options, including splenectomy. The patient asks if there are any means by which to predict likelihood of response to splenectomy. You have heard about the use of indium-labeled autologous platelet scanning for this purpose and wonder what the evidence shows.

  7. STUDY OF THE INFLUENCE OF COMPLEX TREATMENT USING IMMUNOMODULATORS ON THE STATE OF LOCAL IMMUNITY IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS I-II SEVERITY ON ENTEROBIASIS

    OpenAIRE

    2016-01-01

    Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were...

  8. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong

    2010-01-01

    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  9. Loss of the TGFβ-activating integrin αvβ8 on dendritic cells protects mice from chronic intestinal parasitic infection via control of type 2 immunity.

    Directory of Open Access Journals (Sweden)

    John J Worthington

    Full Text Available Chronic intestinal parasite infection is a major global health problem, but mechanisms that promote chronicity are poorly understood. Here we describe a novel cellular and molecular pathway involved in the development of chronic intestinal parasite infection. We show that, early during development of chronic infection with the murine intestinal parasite Trichuris muris, TGFβ signalling in CD4+ T-cells is induced and that antibody-mediated inhibition of TGFβ function results in protection from infection. Mechanistically, we find that enhanced TGFβ signalling in CD4+ T-cells during infection involves expression of the TGFβ-activating integrin αvβ8 by dendritic cells (DCs, which we have previously shown is highly expressed by a subset of DCs in the intestine. Importantly, mice lacking integrin αvβ8 on DCs were completely resistant to chronic infection with T. muris, indicating an important functional role for integrin αvβ8-mediated TGFβ activation in promoting chronic infection. Protection from infection was dependent on CD4+ T-cells, but appeared independent of Foxp3+ Tregs. Instead, mice lacking integrin αvβ8 expression on DCs displayed an early increase in production of the protective type 2 cytokine IL-13 by CD4+ T-cells, and inhibition of this increase by crossing mice to IL-4 knockout mice restored parasite infection. Our results therefore provide novel insights into how type 2 immunity is controlled in the intestine, and may help contribute to development of new therapies aimed at promoting expulsion of gut helminths.

  10. GAKG-RGEKG an Epitope That Provokes Immune Cross-Reactivity between Prevotella sp. and Human Collagen: Evidence of Molecular Mimicry in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Gustavo Alberto Obando-Pereda

    2016-01-01

    Full Text Available Periodontal disease afflicts 20% of world population. This process usually occurs in the form of being lethargic and chronic, and consequently this disease is known as chronic process. All chronic diseases constantly cause activation of the immune system, and therefore the presentation of microbial peptides which are presented to lymphocytes by professional antigen presenting cells can present microbial peptides very similar to important structures of human economy causing autoimmune diseases, process known as molecular mimicry. Thus, the aim of this study was to verify the presence of molecular mimicry phenomenon between periodontopathogens and human proteins. Blasting microbes of Socransky periodontal complexes against human collagen were performed and then the proteins with similarities were modelled and were screened in the MHI binding virtual methods. The epitopes selected were produced and plasma of chronic periodontal volunteers was obtained and a dot immunobinding assay was performed. Hypothetical protein of Prevotella sp. and human collagen epitopes with high similarities were positive for dot immunobinding assay. With this result it can be suggested that the mimicry phenomena can occur on periodontal disease.

  11. COPD免疫紊乱与慢性炎症持续存在的关系%The Relationship Between Immune Disorders and Chronic Inflammation in COPD

    Institute of Scientific and Technical Information of China (English)

    牛永亮(综述); 陈兴无(审校)

    2016-01-01

    Chronic obstructive pulmonary disease ( COPD) is one of the most common diseases of the respiratory, with a gradual development. Avoiding inhaling harmful gas and medication do not prevent decline in lung function because of persistence of chronic in-flammation, which is associated with innate immunity disorders and frequent infections in the lungs of patients. Effective treatment strategies should be focused on restoring the innate immune system function.%慢性阻塞性肺疾病为呼吸科常见疾病,病情呈现逐渐性进展,药物治疗及避免有害气体接触并不能阻止肺功能下降,提示患者肺内慢性炎症持续存在,其原因与固有免疫紊乱、病原体反复感染有关。有效的治疗策略应注重恢复固有免疫系统功能。

  12. 慢性肾脏病及透析患儿的疫苗接种%Immunization in children with chronic renal diseases and undergoing dialysis

    Institute of Scientific and Technical Information of China (English)

    刘小荣; 姚开虎; 杨永弘

    2013-01-01

    Most children patients with chronic kidney disease show immune disorders and defects of immune functionality.There are significant increases in various pathogen infections,especially streptococcus pneumonia,hepatitis B virus,and influenza virus.Streptococcus pneumonia is the most common cause of bacterial pneumonia and otitis media worldwide,and the main pathogens of bacterial meningitis as well.Children treated by hemodialysis are in high risk circumstance susceptible to hepatitis B virus.Influenza is a highly contagious disease with extremely strong dissemination capability.The organizations of U.S.Advisory Committee on Immunization Practices (ACIP),and Kidney Disease:Improving Global Outcomes (KDIGO) specifically recommends 3 vaccines,namely,hepatitis B virus,influenza virus (inactivated),and pneumococcal vaccine for patients with chronic kidney disease and chronic dialysis.Vaccination is a specific preventive and an effective protective measure for patients of chronic kidney disease and undergoing dialysis.%慢性肾脏病患儿大多存在免疫紊乱及免疫功能缺陷.各种病原菌的感染率明显增高,尤其容易感染肺炎链球菌、HBV及流感病毒.在全球范围内,肺炎链球菌是细菌性肺炎和中耳炎的最常见病原,是细菌性脑膜炎的主要病原菌.血液透析的患儿更是HBV易感染的高危人群.流感是具有高度传染性及极其广泛的传播性疾病.美国免疫实践指南咨询委员会(ACIP)及改善全球肾脏病预后(KDIGO)特别推荐慢性肾脏病及慢性透析的患者接种的3种疫苗是HBV疫苗、灭活流感病毒疫苗及肺炎链球菌疫苗.接种疫苗是特异性的预防措施,可对慢性肾脏病及透析患者提供有效的预防保护.

  13. The effects of grounding (earthing on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Oschman JL

    2015-03-01

    Full Text Available James L Oschman,1 Gaétan Chevalier,2 Richard Brown3 1Nature’s Own Research Association, Dover, NH, USA; 2Developmental and Cell Biology Department, University of California at Irvine, Irvine, CA, USA; 3Human Physiology Department, University of Oregon, Eugene, OR, USA Abstract: Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1 inform researchers about what appears to be a new perspective to the study of inflammation, and 2 alert researchers that the length of time and degree (resistance to ground of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation. Keywords: chronic inflammation, immune system, wound repair, white blood cells, macrophages, autoimmune disorders

  14. Squamous cell carcinoma larynx presenting as idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Bekur R

    2015-01-01

    Full Text Available Association of immune thrombocytpenic purpura with solid malignancy as paraneoplastic manifestation has been reported earlier mainly with lymphoma and breast cancer. We report the case of a patient with squamous cell carcinoma of the larynx presenting with idiopathic thombocytopenic purpura (ITP. A 67-year-old lady presented with multiple ecchymotic patches and petechiae all over the body and bleeding from oral cavity was found to have severe thrombocytopenia diagnosed as ITP with bone marrow evidence of peripheral destruction without infiltration of bone marrow. Five months later she was diagnosed to have squamous cell carcinoma of larynx. Platelet count improved after splenectomy.

  15. Pulmonary histoplasmosis presenting as chronic productive cough, fever, and massive unilateral consolidation in a 15-year-old immune-competent boy: a case report

    Directory of Open Access Journals (Sweden)

    Mshana Stephen E

    2011-08-01

    Full Text Available Abstract Introduction Severe histoplasmosis is known to be among the AIDS-defining opportunistic infections affecting patients with very low CD4 cell counts in histoplasmosis-endemic areas. Histoplasma capsulatum var. duboisii is common in West and Central Africa, where it occurs in both HIV/AIDS and non-HIV patients. Few cases of life-threatening histoplasmosis in immune-competent individuals have been reported worldwide. Case report We describe a case of pulmonary histoplasmosis diagnosed on the basis of autopsy and histological investigations. A 15-year old East African immune-competent boy with a history of smear-positive tuberculosis and a two-year history of rock cutting presented to our hospital with chronic productive cough, fever, and massive unilateral consolidation. At the time of presentation to our hospital, this patient was empirically treated for recurrent tuberculosis without success, and he died on the seventh day after admission. The autopsy revealed a huge granulomatous lesion with caseation, but no acid-fast bacilli were detected on several Ziehl-Neelsen stains. However, periodic acid-Schiff staining was positive, and the histological examination revealed features suggestive of Histoplasma yeast cells. Conclusion Severe pulmonary histoplasmosis should be considered in evaluating immune-competent patients with risk factors for the disease who present with pulmonary symptoms mimicking tuberculosis.

  16. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2016-11-01

    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  17. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.

    Science.gov (United States)

    Tamary, Hannah; Roganovic, Jelena; Chitlur, Meera; Nugent, Diane J

    2010-07-01

    The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

  18. The absolute recommendation of chamber Neubauer method for platelets counting instead of indirect methods in severe thrombocytopenic patients

    Directory of Open Access Journals (Sweden)

    Oliveira Raimundo Antônio Gomes

    2003-01-01

    Full Text Available Accurate and precise platelet counting is crucial for recommending platelets transfusion for thrombocytopenic patients, principally when platelet counts are bellow 30,000/µl. As most laboratories still use the indirect methods for confirming low automated platelet counts, this work compared two indirect methods used in practice (Fonio and Nosanchunk et al. with the International Committee for Standardization in Hematology recommended direct method (Brecher and Cronkite. The obtained data show that the indirect methods present low precision and accuracy, and that the direct method should always be employed in severe thrombocytopenic samples thanks to its high precision.

  19. Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response.

    Science.gov (United States)

    Whary, M T; Morgan, T J; Dangler, C A; Gaudes, K J; Taylor, N S; Fox, J G

    1998-07-01

    Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-gamma) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-gamma in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.

  20. Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates.

    Science.gov (United States)

    Dahl, J; Husebekk, A; Acharya, G; Flo, K; Stuge, T B; Skogen, B; Straume, B; Tiller, H

    2016-02-01

    In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti-HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected.

  1. Pseudo-thrombotic thrombocytopenic purpura: A rare presentation of pernicious anemia

    Directory of Open Access Journals (Sweden)

    Ashvin K Tadakamalla

    2011-01-01

    Full Text Available Context: Schistocytes are fragmented red blood cells due to the flow of blood through damaged capillaries and indicate endothelial injury. They are typical of microangiopathic hemolytic anemia seen in life threatening conditions like disseminated intravascular coagulation or thrombotic thrombocytopenic purpura/hemolytic uremic syndrome .We report a rare sub-acute presentation of pernicious anemia with hemolysis, thrombocytopenia and numerous schistocytes that was initially diagnosed as a more serious thrombotic thrombocytopenic purpura. Case Report : A 31-year-old Caucasian woman presented with fatigue and paresthesia of both feet for 1 week. Past medical history included hypertension and gastro-esophageal reflux disease. Examination revealed scleral icterus and pallor. Examination of the abdomen did not show hepatosplenomegaly. Initial laboratory tests showed severe anemia, and low platelets. Indirect bilirubin and serum Lactate De Hydrogenase were elevated. Prothrombin time, partial thromboplastin time, serum fibrinogen, and serum fibrin degradation product levels were normal. Peripheral smear revealed numerous schistocytes, anisocytosis and macro-ovalocytes. Thrombotic thrombocytopenic purpura (TTP was suspected due to the constellation of sub-acute onset of fatigue and paresthesia along with thrombocytopenia, schistocytes and an elevated LDH. Plasmapheresis was initiated for possible TTP. However, platelet count worsened despite plasmapheresis for 4 days. On re-evaluation, vitamin B 12 was found to be low. Treatment with intra-muscular vitamin B 12 led to symptomatic and hematologic improvement. Pernicious anemia was confirmed by the presence of anti-intrinsic factor antibodies, elevated serum gastrin level and atrophic gastritis. Conclusion : Clinicians must be aware of unusual clinical presentation of vitamin B 12 deficiency with schistocytes as the management is simple and effective.

  2. 601 Autoimmune Thrombocytopenic Purpura Associated with Common Variable Immunodeficiency

    Science.gov (United States)

    Mendieta, Elizabeth; Del Rivero, Leonel Gerardo

    2012-01-01

    Background Common variable immunodeficiency (CVID) is a condition characterized by antibody deficiency, and therefore susceptible to recurrent pyogenic infections, cancer and autoimmune diseases. It is a heterogeneous syndrome in primary immunodeficiencies and clinically the most important is often diagnosed in adulthood. Autoimmunity occurs in 5% of the general population, in patients with CVID the percentage increased to 20 to 48%, cytopenias being the most common cause of autoimmunity in these patients. Autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune consequences, occurring in 5% to 8% of all patients with CVID. Some patients develop these disorders before the diagnosis of CVID. Methods We present the case of a woman of 45 year old, with a history of lower respiratory tract and urinary tract infections in recurrent Pulmonary Tuberculosis. Enter the program short-course treatment strictly supervised for pulmonary tuberculosis with appropriate response. Autoinmune thrombocytopenic purpura refractory to steroids (WWTP) for performing splenectomy. Results Anti DNA antibodies, anti nuclear, anti-protease, C. ANCA/PR3 antimieloperoxidasa, serology for hepatitis B, C, HIV negative. Serum immunoglobulins were as follow: IgG, 158 mg/dL (normal 700 to 1600), IgM, 55 mg/dL (normal 40–230), IgA, 36 mg/dL (normal 70–400), and, IgE, 38.7 IU/mL (normal 0–100) in more than 2 occasions with values below 2 standard deviations. CD4 T lymphocytes (19%) CD4/CD8 ratio (0.54). Conclusions Meets diagnostic criteria for Common Variable Immunodeficiency (CVID) and starting treatment with intravenous immunoglobulin at a dose of 400 mg/kg (every 21 days) with significant clinical improvement and has even managed to integrate into your daily activities. Today, he continues with danazol for WWTP. Therefore, CVID is necessary to consider in the differential diagnosis of autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia

  3. Severe Thrombocytopenic Purpura in a Child with Brucellosis: Case Presentation and Review of the Literature

    Science.gov (United States)

    Perogiannaki, Aikaterini; Chaliasos, Nikolaos

    2017-01-01

    Brucellosis is still endemic and a significant public health problem in many Mediterranean countries, including Greece. It is a multisystemic disease with a broad spectrum of clinical manifestations including hematological disorders, such as anemia, pancytopenia, leucopenia, and thrombocytopenia. Thrombocytopenia is usually moderate and attributed to bone marrow suppression or hypersplenism. Rarely, autoimmune stimulation can cause severe thrombocytopenia with clinically significant hemorrhagic manifestations. We present the case of a girl with severe thrombocytopenic purpura as one of the presenting symptoms of Brucella melitensis infection. Treatment with intravenous immunoglobulin and the appropriate antimicrobial agents promptly resolved the thrombocyte counts. A review of similar published cases is also presented. PMID:28127481

  4. Crohn’s Disease and Idiopathic Thrombocytopenic Purpura in a Patient with Ectodermal Dysplasia and Immunodeficiency

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    Farzaneh Motamed

    2006-09-01

    Full Text Available In this case report we will describe a rare association between anhyrotic ectodermal dysplasia (AED and immunodeficiency and autoimmunity [in our case: Idiopathic Thrombocytopenic Purpura (ITP and Crohn disease]. AED is a rare congenital disorder characterized by sparse hair, abnormal teeth and anhidrosis due to lack of eccrine glands. The survey of 87 cases with (AED revealed only one Irritable Bowel Disease (IBD.  AED has only two relevancies with immunodeficiency: (EDA-ID: Ectodermal Dysplasia Anhyrotic with Immunodeficiency and APE-CED (Autoimmune polyendocrinopathy, Candidiasis and Ectodermal Dysplasia that in our case EDA-ID is strongly suspected.

  5. Prediction of Response to Immune Modifying Therapy for Patients with Chronic Hepatitis B using Hepatitis B Surface Antigen Levels

    NARCIS (Netherlands)

    V. Rijckborst (Vincent)

    2011-01-01

    textabstractThe treatment of chronic hepatitis B has greatly improved with the introduction of potent nucleos(t)ide analogues with a high barrier to resistance and peginterferon. The advantages and limitations of both treatment options should be considered when a patient has an indication to initiat

  6. Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.

    Science.gov (United States)

    Kelschenbach, Jennifer L; Saini, Manisha; Hadas, Eran; Gu, Chao-Jiang; Chao, Wei; Bentsman, Galina; Hong, Jessie P; Hanke, Tomas; Sharer, Leroy R; Potash, Mary Jane; Volsky, David J

    2012-06-01

    Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

  7. An insidious presentation of thrombotic thrombocytopenic purpura:A case report and brief literature review

    Institute of Scientific and Technical Information of China (English)

    Shafeek Kiblawi; Elie Harmouche; Ralph Bou Chebl; Gilbert Abou Dagher

    2014-01-01

    Thrombotic thrombocytopenic purpura(TTP) is a rare thrombotic microangiopathy with an estimated incidence of11 cases/million population per year.Early treatment is essential and is curative in this disease where lack of treatment results in90% mortality.We describe an atypical case of a patient withTTP who presented to theEmergencyDepartment for headache, and was found to have thrombocytopenia but only mild anemia that was explained by another disease process.Case:A44-year-old female presented to theEmergencyDepartment for worsening headache and weakness over the last week.She had no fever and no focal neurological deficits but was pale and complained of severe headache.A blood test showed her to be anemic and thrombocytopenic.She explained that she had been having prolonged heavy menses over the last year.She was treated with blood and platelet transfusions, and seen by theGynecology service who treated her for uterine fibroids after which she was discharged.She returned1 week later with the same complaint, and was found to have a stable hemoglobin level but recurrence of thrombocytopenia.ATTP diagnosis was entertained and the workup confirmed it.The patient was treated with plasmapheresis and discharged home with no sequalae.Conclusion:Emergency physicians should keepTTP in mind when approaching cases of thrombocytopenia with mild anemia, even if an alternative diagnosis exists.

  8. Effects of prednisone and splenectomy in patients with idiopathic thrombocytopenic purpura : only splenectomy induces a complete remission

    NARCIS (Netherlands)

    Louwes, H; Vellenga, E; Houwerzijl, EJ; de Wolf, JTM

    2001-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous disease, whereby it is unclear if and in which way prednisone and splenectomy affect the platelet kinetics leading to a complete remission. To determine the effects of prednisone and splenectomy on the mean platelet life (MPL) and platelet

  9. HCV感染过程中的相关免疫反应%Innate and adaptive immune responses in chronic HCV infection

    Institute of Scientific and Technical Information of China (English)

    姚敏(综述); 吕欣(审校)

    2016-01-01

    丙型肝炎病毒( Hepatitis C Virus, HCV)是慢性丙型病毒性肝炎的主要病因,也是引发肝硬化和肝癌的主要诱因。在HCV感染过程中,伴随着干扰素信号通路的激活和干扰素刺激基因( IFN-stimulated gene,ISG)的持续表达,且有HCV独特的免疫逃逸和免疫细胞的功能损伤。现就HCV感染过程中机体的固有免疫反应和适应性免疫反应的研究进展作一综述。%Hepatitis C virus ( HCV) is a leading cause for chronic hepatitis C , which is also a major inducing cause to re-sult in cirrhosis and hepatocellular carcinoma. In the process of HCV infection, along with activated interferon signaling pathways and constitutive IFN-stimulated gene( ISG) expression, both the viral escape from the immune responses and dys-function of NK and T cell most likely contribute to the ongoing liver disease. In this review, we will summarize current knowledge about the role of innate and adaptive immune responses in HCV infection.

  10. Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

    Science.gov (United States)

    Bernard, François-Xavier; Morel, Franck; Camus, Magalie; Pedretti, Nathalie; Barrault, Christine; Garnier, Julien; Lecron, Jean-Claude

    2012-01-01

    Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies. PMID:23193414

  11. Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    François-Xavier Bernard

    2012-01-01

    Full Text Available Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies.

  12. Restoration of Innate and Adaptive Immune Responses by HCV Viral Inhibition with an Induction Approach Using Natural Interferon-Beta in Chronic Hepatitis C

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    Y. Kishida

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC for 48 weeks (novel combination treatment: NCT would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT. Serum cytokine and chemokine levels were evaluated during NCT. NCT prevented viral escape and breakthrough resulting in persistent viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in both early virologic responders (EAVRs and late virologic responders (LAVRs; CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (<0.05 in EAVR but not in LAVR during NCT, and IL-12 increased significantly (<0.05 and CXCL-8 decreased significantly (<0.05 after the end of NCT in EAVR but not in LAVR. NCT prevented viral breakthrough with viral clearance leading to improvement of innate and adaptive immunity resulting in a sustained virologic response (SVR. NCT (=8 achieved a higher SVR rate than SOC (=8 in difficult-to-treat CHC patients with genotype 1 and high viral loads.

  13. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Simona Granata

    2016-01-01

    Full Text Available Chronic kidney disease (CKD is an increasing and global health problem with a great economic burden for healthcare system. Therefore to slow down the progression of this condition is a main objective in nephrology. It has been extensively reported that microinflammation, immune system deregulation, and oxidative stress contribute to CKD progression. Additionally, dialysis worsens this clinical condition because of the contact of blood with bioincompatible dialytic devices. Numerous studies have shown the close link between immune system impairment and CKD but most have been performed using classical biomolecular strategies. These methodologies are limited in their ability to discover new elements and enable measuring the simultaneous influence of multiple factors. The “omics” techniques could overcome these gaps. For example, transcriptomics has revealed that mitochondria and inflammasome have a role in pathogenesis of CKD and are pivotal elements in the cellular alterations leading to systemic complications. We believe that a larger employment of this technique, together with other “omics” methodologies, could help clinicians to obtain new pathogenetic insights, novel diagnostic biomarkers, and therapeutic targets. Finally, transcriptomics could allow clinicians to personalize therapeutic strategies according to individual genetic background (nutrigenomic and pharmacogenomic. In this review, we analyzed the available transcriptomic studies involving CKD patients.

  14. Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: possible implication for TLR4-signalling and chronic immune activation.

    Science.gov (United States)

    Trøseid, Marius; Lind, Andreas; Nowak, Piotr; Barqasho, Babilonia; Heger, Bernt; Lygren, Idar; Pedersen, Karin K; Kanda, Tatsuo; Funaoka, Hiroyuki; Damås, Jan K; Kvale, Dag

    2013-06-01

    Progressive HIV infection is characterized by profound enterocyte damage, microbial translocation and chronic immune activation. We aimed to test whether High Mobility Group Box protein 1(HMGB1), a marker of cell death, alone, or in combination with LPS, might contribute to HIV-associated immune activation and progression. Altogether, 29 untreated HIV-infected individuals, 25 inflammatory bowel disease (IBD) patients and 30 controls were included. HIV-infected patients had lower plasma LPS levels than IBD patients, but higher levels of soluble CD14 and Myeloid Differentiation (MD) 2, which interacts with TLR4 to initiate LPS-signalling. Furthermore, plasma levels of HMGB1 and MD2 were correlated directly within the HIV-infected cohort (r = 0.89, P < 0.001) and the IBD-cohort (r = 0.85, P < 0.001), implying HMGB1 signalling through the MD2/TLR4-pathway. HMGB1 and LPS, although not inter-correlated, were both moderately (r = 0.4) correlated with CD38 density on CD8+ T cells in HIV progressors. The highest levels of CD38 density and MD2 were found in progressors with plasma levels of both LPS and HMGB1 above the fiftieth percentile. Our results could imply that, in some patients, immune activation is triggered by microbial translocation, in some by cell death and in some by HMGB1 in complex with bacterial products through activation of the MD2/TLR4-pathway.

  15. Chronic granulomatous disease

    Science.gov (United States)

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called phagocytes are unable to kill some types of bacteria and ...

  16. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)

    2012-07-01

    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  17. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.

    Science.gov (United States)

    Weiner, A J; Geysen, H M; Christopherson, C; Hall, J E; Mason, T J; Saracco, G; Bonino, F; Crawford, K; Marion, C D; Crawford, K A

    1992-01-01

    E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV. PMID:1314389

  18. Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Concern about costs and antiretroviral therapy (ART-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI. Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk. METHODOLOGY: ACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with or=500 cells/microL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2 (cycle = 4.5 million IU sc BID x 5 days every 8 weeks. After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/microL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels. PRINCIPAL FINDINGS: By week 8 of TI, levels of total cholesterol (TC (median (Q1, Q3 (-0.73 (-1.19, -0.18 mmol/L, p<0.0001, LDL, HDL cholesterol (-0.36(-0.73,-0.03mmol/L, p = 0.0007 and -0.05(-0.26,0.03, p = 0.0033, respectively and triglycerides decreased (-0.40 (-0.84, 0.07 mmol/L, p = 0.005. However the TC/HDL ratio remained unchanged (-0.09 (-1.2, 0.5, p = 0.2. Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively. After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43, p<0.0001 and soluble TNFR2 (1089 ng/L (-189, 1655, p = 0.0008 coinciding with the rebound of HIV viremia. CONCLUSIONS: Our data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic

  19. Splenectomy in patients with idiopathic thrombocytopenic purpura: Analysis of 109 cases

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    Enver Ay

    2012-03-01

    Full Text Available Objectives: Splenectomy is performed in order to provide the treatment in the patients with severe idiopathic thrombocytopenic purpura, refractory to medical treatment. In this study, we aimed to investigate the postoperatif and longterm outcomes in the patients who underwent splenectomy with the diagnosis of idiopathic thrombocytopenic purpura.Materials and Methods: Between 2001-2010 at Dicle University Medical Faculty, General Surgery Department, a retrospective review of the 109 patients who had undergone splenectomy for ITP was reviewed. Age, gender, presence of accessory spleens and location, duration of the operation, number of preoperative platelet tranfusion, number of preoperative and postoperative blood transfusion, length of hospital stay, long-term outcomes, morbidity and mortality were recorded.Results: The mean age was 37.10 ± 16.62 (16-72, and there were 88 (80.7% female and 21 (19.3% male patients. The mean operation time was 44.87 ± 10:32 (30-120 minutes. The average postoperative blood and preoperative platelet transfusion were 1.63 ± 0.85 (0-3 and 2.01 ± 0.71 (1-3 units, respectively. The accessory spleens were encountered in 20 (18.3% patients at the ultrasonographic examination. And also the accessory spleens were encountered in 23 (21.1% patients during operation and confirmed with histopathologic examination. The most common localization of accessory spleens were splenic hilus. The postoperative complications were occurred in 16 patients (14.7% and the most complication was atelectasia. The mean length of hospital stay was 4:56 ± 2:45 (2-12 days. Patients were followed for an average of 28 (9-48 months. At the follow-up period, 1 (0.9 % patient had died.Conclusion: Splenectomy can be performed safely in the treatment of the patients with idiopathic thrombocytopenic purpura unresponsive to medical treatment. Long-term good results can be obtained with splenectomy in these patients. The accessory spleens should not be

  20. Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis

    Science.gov (United States)

    Kennedy, Joshua L.; Steinke, John W.; Liu, Lixia; Negri, Julie; Borish, Larry

    2016-01-01

    Background: T-helper (Th) type 2 cell inflammation is the hallmark of several disease processes, including asthma, atopic dermatitis, and some forms of chronic rhinosinusitis. Itraconazole has been used as both an antifungal and an anti-inflammatory agent, with some success in many of these diseases, in part, by altering Th2 cytokine expression by T cells. It is not known whether this merely reflects inhibition of established Th2-like cells or the inhibition of differentiation of naive T cells into Th2-like cells. Objective: To evaluate the role of itraconazole in the differentiation of naive T cells during activation. Methods: Naive CD45RA+ T cells were isolated from peripheral blood mononuclear cells from healthy volunteers. Th1 and Th2 type cells were differentiated in the presence of varying concentrations of itraconazole. After stimulation with anti-CD3 and anti-CD28 beads, carboxyfluorescein succinimidyl ester dilution was performed to evaluate proliferation and intracellular cytokine staining for interleukin (IL) 4 and interferon (IFN) gamma within proliferating T cells was measured along with enzyme-linked immunosorbent assay for secreted IL-5, IL-13, and IFN gamma. Results: Itraconazole had no effect on proliferation of unbiased, Th1, or Th2 cells. Similarly, there was no effect of itraconazole on either intracellular cytokine staining of IL-4 and IFN gamma or secreted cytokine expression of IFN gamma, IL-5, and IL-13 in any of the cell populations. Conclusion: Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.

  1. 477 Autoimmunity in Patients with Allergy and Immunodeficiency: as Result of the Immune Chronic Inflammation

    Science.gov (United States)

    Mendez-Inocencio, Julia; Bellanti, Joseph

    2012-01-01

    Background Autoimmunity is present in several patients that have allergy and immunodeficiency; however there are few reports that correlate these 3 immunological problems. Our objective was to study the association of these 3 problems where the deregulation of the T reg cells has a roll in triggering a chronic inflammation and the clinical expression. Methods We included 8 patients with symptoms of autoimmune disease, such as autoimmune hypothyroidism, dermatomiositis, systemic vasculitis, autoimmune uveitis, Wegener´s granulomatosis, antiphospholipid syndrome, Kawasaki´s disease and SLE with allergic disease and T and B lymphocytes immunodeficiency. We did the clinical history, skin test and also immunological evaluation with immunoglobulins, IgG subclasses, T lymphocytes absolute numbers and specific antibodies, all of them had diagnosis of allergy, with immunodeficiency and autoimmune disease. Results There were included 8 patients, with moderate to severe allergy and recurrent infections, from 3 to 66 years of age, 1 child (12.5%) and 7 adults (87.5%), 7 women (93.3%), 1 men (12.5%) with allergic rhinitis 8 (100%), combination of allergic rhinitis and other allergic disease 2 (25%), asthma 1 (12.5%), atopic dermatitis 1 (12.5%). Also all the 8 patients had humoral, cellular immunodeficiency and autoimmune problems, 7 of them received IVIG therapy on the basis of the immunodeficiency, with evident improvement, 1 did not received and had some improvement of their symptoms. Conclusions We found out that the 8 patients with autoimmunity had allergy and also mixed T and B immunodeficiency. We conclude that the physicians should be aware of the correlation in chronic inflammation and the presence of the 3 immunological clinical problems to give appropriate treatment and improve the prognosis of these patients.

  2. Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

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    Elisabetta Loggi

    Full Text Available BACKGROUND AIMS: The immune impairment characterizing chronic hepatitis B (cHBV infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. METHODS: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. RESULTS: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. CONCLUSIONS: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

  3. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection.

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    Guadalupe, Moraima; Sankaran, Sumathi; George, Michael D; Reay, Elizabeth; Verhoeven, David; Shacklett, Barbara L; Flamm, Jason; Wegelin, Jacob; Prindiville, Thomas; Dandekar, Satya

    2006-08-01

    Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11 alpha, alpha(E)beta 7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

  4. Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

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    Niaz Faraz

    2010-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.

  5. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura

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    Jorge García-Méndez

    2016-01-01

    Full Text Available Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis.

  6. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

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    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  7. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

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    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  8. Immunological and antiviral responses after therapeutic DNA immunization in chronic hepatitis B patients efficiently treated by analogues.

    Science.gov (United States)

    Godon, O; Fontaine, H; Kahi, S; Meritet, Jf; Scott-Algara, D; Pol, S; Michel, Ml; Bourgine, M

    2014-03-01

    A substudy of a phase I/II, prospective, multicenter clinical trial was carried out to investigate the potential benefit of therapeutic vaccination on hepatitis B e antigen-negative patients with chronic hepatitis B (CHB), treated efficiently with analogues. Patients were randomized in 2 arms, one receiving a hepatitis B virus (HBV) envelope DNA vaccine, and one without vaccination. At baseline, HBV-specific interferon (IFN)-γ-producing T cells were detected in both groups after in vitro expansion of peripheral blood mononuclear cells. Vaccine-specific responses remained stable in the vaccine group, whereas in the control group the percentage of patients with HBV-specific IFN-γ-producing T cells decreased over time. The vaccine-specific cytokine-producing T cells were mostly polyfunctional CD4(+) T cells, and the proportion of triple cytokine-producer T cells was boosted after DNA injections. However, these T-cell responses did not impact on HBV reactivation after stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation.

  9. Chronic immune activation in HIV-1 infection contributes to reduced interferon alpha production via enhanced CD40:CD40 ligand interaction.

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    Norbert Donhauser

    the conclusion that the chronic immune activation in HIV-1 infection impairs peripheral PDC innate immune responses at least in part via enhanced CD40:CD40L interactions.

  10. The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients

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    Novo Carlos

    2008-09-01

    Full Text Available Abstract Background This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2–4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity Results The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%, increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. Conclusion The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size

  11. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    Science.gov (United States)

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients.

  12. Case of twin pregnancy complicated by idiopathic thrombocytopenic purpura treated with intravenous immunoglobulin: Review of the literature.

    Science.gov (United States)

    Zhao, W X; Yang, X F; Lin, J H

    2017-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia without other clear cause of thrombocytopenia. It is not common in a singleton pregnancy and less common in twin pregnancy. We report a 33-year-old ITP pluripara whose first pregnancy was uneventful. She carried twin pregnancy, complicated by recurrent very low platelets, and gave birth to preterm twins. This patient received multiple courses of intravenous immunoglobulin (IVIG) and showed a significant platelet count improvement with IVIG therapy.

  13. The relationship between T CD4+ cells count and IL-17, IL-11 serum level in idiopathic thrombocytopenic purpura

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    Nayereh Alizadeh

    2014-04-01

    Conclusion: In summary, our study indicated a role of IL-11 in ITP patients, also showed that ITP may not be associated with changes of plasma IL-17 levels and T CD4+ cells count relative to control population. Therefore, measurement of plasma IL-11 levels may be important criteria in development of ITP. In addition, it is concluded that determination of IL-11 can be a diagnostic marker to recognize thrombocytopenic purpura patients.

  14. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    Science.gov (United States)

    Mortensen, Thomas Bech; Frederiksen, Henrik; Marcher, Claus Werenberg; Preiss, Birgitte

    2017-01-04

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

  15. STUDY OF THE INFLUENCE OF COMPLEX TREATMENT USING IMMUNOMODULATORS ON THE STATE OF LOCAL IMMUNITY IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS I-II SEVERITY ON ENTEROBIASIS

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    Savel’eva NN

    2016-12-01

    Full Text Available Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were treated according to our scheme. The control group consisted of 30 people with СGP I degree and 58 people with СGP II severity, treated with conventional treatment. The control group consisted of 30 people without periodontal disease and chronic diseases of other systems. All patients were studied the main group and the comparison group conducted a basic local therapeutic treatment of periodontal disease, including professional oral hygiene, temporary splinting of teeth, selective prishlifovyvanie teeth. For medical treatment of periodontal tissues using 0.05% - 0.2% solution of chlorhexidine bigluconate. Further treatment of patients of the main group carried out in 2 stages. At the first stage the main group received: irrigation and instillation of periodontal tissue in periodontal pockets antiseptic preparation "Dekasan" application keratoplastic drug "Katomas". Systemically administered drug tonic "Sage oil" probiotic "Kvertulin" immunomodulator "Erbisol". In the second phase, patients received: applications on the gums periodontal gel "Lizomukoid" systemically complex preparation "Оil extract from pumpkin seeds." All patients of the main group used toothpaste "Lacalut flora" and rinse "grapefruit". In the comparison group, patients received applications in periodontal pockets (drug Dalatsin C application to the gums (keratoplastic drug Aekol system - a probiotic Linex, immunomodulator "Echinacea compositum С". All patients with the comparison group

  16. Analysis of difference in expression profiles of microRNA molecules in the liver between immune tolerance and immune clearance phase of chronic hepatitis B virus infection%慢性HBV感染免疫耐受期与免疫清除期肝组织微小RNA表达谱差异分析

    Institute of Scientific and Technical Information of China (English)

    李强; 张小楠; 卓其斌; 黄玉仙; 陈良

    2015-01-01

    目的:探索慢性HBV感染免疫耐受期及免疫清除期肝组织微小RNA(miRNA)表达谱的差异并探讨其临床意义。方法应用miRNA芯片筛选9例HBV感染免疫耐受期、8例 HBV感染免疫清除期及6例健康对照者肝组织miRNA分子表达谱,进行组间两两比较后,筛选出肝组织中差异表达的miRNA。结果与健康对照组相比,慢性HBV感染免疫耐受期肝组织中miRNA分子上调9个,下调6个;慢性 HBV感染免疫清除期肝组织中miRNA分子上调8个,下调6个。与慢性 HBV感染免疫耐受期相比,免疫清除期肝组织中miRNA分子上调6个,下调1个。结论慢性HBV感染免疫耐受期和免疫清除期肝组织差异表达的miRNA可能与HBV感染后的免疫清除过程密切相关,有可能成为临床鉴别慢性HBV感染免疫耐受和免疫清除状态的新型分子标记。%Objective To explore the difference in expression profiles and their clinical significance of microRNA molecules in the liver between immune tolerance and immune clearance phase of chronic hepatitis B vius (HBV) infection . Methods The miRNA molecules expressions of 9 immune‐tolerance patients ,8 immune‐clearance patients of chronic HBV infection ,and 6 healthy controls were screened using miRNA microarray . The difference in expression profiles of microRNA molecules in the liver was screened out through comparison among groups .Results Compared with the healthy controls ,significant differences were found in the expression profiles of miRNA molecules in the liver in immune tolerance phase (9 molecules up‐regulated ,and 6 down‐regulated) and immune clearance phase(8 molecules up‐regulated ,and 6 down‐regulated) of chronic HBV infection .Compared with immune tolerance phase ,6 molecules up‐regulated and 1 down‐regulated in the immune clearance phase .Conclusion The abnormal expression profiles of miRNAs in the liver between immune tolerance phase and immune clearance phase

  17. Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B

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    Wenjin Zhang

    2012-08-01

    Full Text Available Abstract Background Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response. Methods Fifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load. Results ]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range

  18. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease.

    Science.gov (United States)

    Breger, Ludivine S; Kienle, Korbinian; Smith, Gaynor A; Dunnett, Stephen B; Lane, Emma L

    2017-03-01

    Although intrastriatal transplantation of fetal cells for the treatment of Parkinson's disease had shown encouraging results in initial open-label clinical trials, subsequent double-blind studies reported more debatable outcomes. These studies highlighted the need for greater preclinical analysis of the parameters that may influence the success of cell therapy. While much of this has focused on the cells and location of the transplants, few have attempted to replicate potentially critical patient centered factors. Of particular relevance is that patients will be under continued L-DOPA treatment prior to and following transplantation, and that typically the grafts will not be immunologically compatible with the host. The aim of this study was therefore to determine the effect of chronic L-DOPA administered during different phases of the transplantation process on the survival and function of grafts with differing degrees of immunological compatibility. To that end, unilaterally 6-OHDA lesioned rats received sham surgery, allogeneic or xenogeneic transplants, while being treated with L-DOPA before and/or after transplantation. Irrespective of the L-DOPA treatment, dopaminergic grafts improved function and reduced the onset of L-DOPA induced dyskinesia. Importantly, although L-DOPA administered post transplantation was found to have no detrimental effect on graft survival, it did significantly promote the immune response around xenogeneic transplants, despite the administration of immunosuppressive treatment (cyclosporine). This study is the first to systematically examine the effect of L-DOPA on graft tolerance, which is dependent on the donor-host compatibility. These findings emphasize the importance of using animal models that adequately represent the patient paradigm.

  19. Alleviation of chronic heat stress in broilers by dietary supplementation of betaine and turmeric rhizome powder: dynamics of performance, leukocyte profile, humoral immunity, and antioxidant status.

    Science.gov (United States)

    Akhavan-Salamat, Hossein; Ghasemi, Hossein Ali

    2016-01-01

    Heat stress (HS), one of the most serious climate problems of tropical and subtropical countries, negatively affects the production performance of broilers. Keeping this in view, the current study was aimed at elucidating the effects of supplementing betaine (Bet) and dried turmeric rhizome powder (TRP), either singly or in combination, on growth performance, leukocyte profile, humoral immunity, and antioxidant status in broilers kept under chronic HS. A total of 625 one-day-old Ross male chicks were randomly assigned to five treatment groups (5 replicates of 25 birds per replicate pen). From day 1, the birds were either kept at the thermoneutral zone (TN) or exposed to HS (33 ± 1°C) to the conclusion of study, day 42. THeat stress (HS), one of the most serious climate problems of tropical and subtropical countries, negatively affects the production performance of broilers. Keeping this in view, the current study was aimed at elucidating the effects of supplementing betaine (Bet) and dried turmeric rhizome powder (TRP), either singly or in combination, on growth performance, leukocyte profile, humoral immunity, and antioxidant status in broilers kept under chronic HS. A total of 625 one-day-old Ross male chicks were randomly assigned to five treatment groups (5 replicates of 25 birds per replicate pen). From day 1, the birds were either kept at the thermoneutral zone (TN) or exposed to HS (33 ± 1°C) to the conclusion of study, day 42. The treatment groups were as follows: thermoneutral control (TN-CON), HS-CON, HS-Bet, HS-TRP, and HS-BT (fed Bet and TRP). The results showed that decreases in body weight gain, feed intake, and increases in feed-to-gain ratio and mortality induced by HS were partially restored by dietary supplementation of Bet and TRP. The heterophil/lymphocyte ratio, total, and IgG antibody titers against sheep red blood cell for secondary responses in the HS-TRP and HS-BT groups were also similar to those of the broilers in the TN

  20. Effect of the sequential therapy of lamivudine and α-interferon on cellular immune function as well as serum PD-1 and Tin-3 levels in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Yan Jin; Ting Qiu; Yi-Fei Lyu; Chun-Ying Yan; Xue Wang; Tian-Jiao Duan; Rong Zhang; Gui-Sheng Liu

    2016-01-01

    Objective:To analyze the effect of the sequential therapy of lamivudine and α-interferon on cellular immune function as well as serum PD-1 and Tin-3 levels in patients with chronic hepatitis B. Methods: A total of 92 cases of patients with chronic hepatitis B who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects and divided into observation group and control group (n=46) according to the random number table. Control group received lamivudine treatment alone, observation group received the sequential therapy of lamivudine and α-interferon, and then differences in ultrasound-related indexes, cellular immune function as well as PD-1 and Tin-3 levels were compared between two groups. Results:After observation group received the sequential therapy of lamivudine andα-interferon, ultrasonic major diameter of left hepatic lobe and PVM values were greater than those of control group, and internal diameter of portal vein was lower than that of control group; CD4+T and CD4+T/ CD8+T values of observation group were higher than those of control group, and CD8+T value was lower than that of control group;circulating blood CD8+T cell PD-1 and Tim-3 expression levels of observation group were lower than those of control group. Conclusion:Sequential therapy of lamivudine andα-interferon can optimize the cellular immune function of patients with chronic hepatitis B and inhibit the negative regulation process of immune function, and it helps to inhibit hepatitis B virus activity and disease control.

  1. Inflammatory bowel disease related innate immunity and adaptive immunity

    Science.gov (United States)

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD. PMID:27398134

  2. Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

    Directory of Open Access Journals (Sweden)

    João Tadeu Damian Souto Filho

    2011-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

  3. Pregnancy-associated thrombotic thrombocytopenic purpura with anti-centromere antibody-positive Raynaud's syndrome.

    Science.gov (United States)

    Watanabe, Ryu; Shirai, Tsuyoshi; Tajima, Yumi; Ohguchi, Hiroto; Onishi, Yasushi; Fujii, Hiroshi; Takasawa, Naruhiko; Ishii, Tomonori; Harigae, Hideo

    2010-01-01

    Thrombotic thrombocytopenic purpura (TTP), scleroderma renal crisis (SRC), and hemolysis, elevated liver enzyme levels, and a low platelet count (HELLP) syndrome display common symptoms that include microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Therefore, it is important to distinguish between them because their treatments vary: however, the differential diagnosis is sometimes difficult. We report a 32-year-old woman who was referred to our department for further examination of microangiopathic hemolytic anemia, thrombocytopenia, and a slightly elevated serum creatinine level with anti-centromere antibody-positive Raynaud's syndrome in the early puerperal period. TTP, SRC, and HELLP syndrome were considered in the differential diagnosis, but the measurement of a disintegrin-like metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS 13) activity and its inhibitor level led to the diagnosis of TTP. She was successfully treated by plasma exchange and high-dose prednisolone and angiotensin-converting enzyme inhibitor. If microangiopathic hemolytic anemia and thrombocytopenia are observed in perinatal women or patients with signs of systemic sclerosis, the measurement of ADAMTS13 activity and its inhibitor level are essential for diagnosis and therapeutic choice.

  4. Thrombotic thrombocytopenic purpura (TTP or Moschowitz syndrome: a true hematologic emergency

    Directory of Open Access Journals (Sweden)

    Deborah Melis

    2012-01-01

    Full Text Available Introduction: Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy caused by congenital or inherited disorders involving the processing of the ultra-large forms of von Willebrand factor. As a result, platelet-rich microthrombi form in the small arterial vessels of various organs, particularly those of the brain, heart, and kidneys. The idiopathic autoimmune form of TTP is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, various disseminated malignancies, and drugs. If not promptly treated, TTP is associated with high mortality, making it a true medical emergency. Materials and methods: The article is based on a review of the literature published between January and October of 2009. Its aim is to clarify the diagnosis, treatment, and follow-up of TTP. Results: Diagnostic criteria include the presence of microangiopathic hemolytic anemia associated with thrombocytopenia in the absence of other obvious causes. Assays of ADAMTS13 activity and titration of acquired antibodies against this enzyme are indicated in the follow-up of disease and as prognostic indicators. Treatment centers around daily plasma exchange associated with immunosuppressant drug therapy, particularly steroids and more recently the monoclonal anti-CD20 antibody rituximab. Discussion: Despite improved treatment, TTP is still associated with significant mortality (10—20%, particularly when plasma exchange is initiated late. Relapse also occurs in a substantial proportion of patients (10—40% although the frequency of this outcome may be reduced by rituximab therapy.

  5. Acute pancreatitis-induced thrombotic thrombocytopenic purpura with recurrent acute pancreatitis.

    Science.gov (United States)

    Fujino, Yasuhisa; Inoue, Yoshihiro; Onodera, Makoto; Kikuchi, Satoshi; Sato, Masayuki; Kojika, Masahiro; Sato, Hisaho; Suzuki, Keijiro; Matsumoto, Masanori

    2016-04-01

    Recent successive reports on acute pancreatitis-induced thrombotic thrombocytopenic purpura (TTP) have revealed that TTP-related microvascular damage is an aggravating factor of acute pancreatitis. Here, we report the case of a 26-year-old man diagnosed with acute pancreatitis due to high alcohol consumption. The patient was unconscious as he had taken an overdose of medication, and presented with fever and renal failure due to acute pancreatitis on admission. Although the pancreatitis subsequently improved, the symptoms were still observed; on the next day, he exhibited hemoglobinuria, anemia, and thrombocytopenia. Moreover, general blood examinations indicated the presence of schistocytes and reduced activity of ADAMTS13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13) to 47 %. Thus, the patient was diagnosed with TTP, and plasma exchange was performed. After the development of TTP, the acute pancreatitis recurred, but a severe pathogenesis was prevented by plasma exchange. Thus, ADAMTS13 activity may be useful for predicting a severe pathogenesis of acute pancreatitis. In ADAMTS13-deficient cases, plasma exchange may be an effective technique for preventing aggravation of acute pancreatitis.

  6. Acute renal failure and severe rhabdomyolysis in a patient with resistant thrombotic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Al Qahtani S

    2011-10-01

    Full Text Available Saad Al Qahtani Intensive Care Department, Critical Care Response Team, King Abdulaziz Medical City (KAMC, National Guard Health Affairs; King Saud Bin Abdulaziz University for Health Sciences, College of Medicine, Riyadh, Kingdom of Saudi Arabia Abstract: Thrombotic thrombocytopenic purpura (TTP is a rare, life-threatening disorder. This paper describes the case of a 39-year-old Sudanese male who presented to the emergency room with fever, jaundice, decreased level of consciousness, and worsening kidney function for 7 days, a high lactate dehydrogenase level (1947, severe thrombocytopenia (platelets 8, and numerous schistocytes in the peripheral blood smear. The patient was admitted with a diagnosis of TTP for plasma exchange. Fourteen days later, his creatinine kinase (CK level rose to >50,000 IU; rhabdomyolysis was suggested. Continuous venovenous hemodialysis (CVVHD was started. The patient's CK level remained high, despite CVVHD, until the 6th day, after which this parameter gradually started to decrease. This report highlights a resistant case of TTP that presented with concomitant severe rhabdomyolysis, which demanded aggressive, continuous intervention. Keywords: TTP, CVVHD, continuous venovenous hemodialysis

  7. Emergency Plasmapheresis in a case of ThromboticThrombocytopenic Purpura (TTP

    Directory of Open Access Journals (Sweden)

    Mariaserena Pioli Di Marco

    2013-12-01

    Full Text Available An 84 year-old female was admitted to our Department of Vascular Internal Medicine after a sudden onset of weakness on her right side and aphasia along with signs of myocardial ischemia from Electrocardiogram (EKG. Clinical and blood exams led to a suspicion of Moschcowitz syndrome, which was reinforced by the presence of numerous schistocytes on a peripheral blood smear.Due to a rapid deterioration of vital signs as well as alertness, the patient underwent an emergency transfusion and plasmapheresis treatment as recommended by American Society of Apheresis (ASFA guidelines: one plasma volume was replaced with fresh frozen plasma (FFP every 24 hours, for the first eight days, in order to reach at least a level of 150,000 platelets/mm3 over three consecutive days accompanied by a decrease in LDH until to 670 UI/l.After this therapy, the clinical picture significantly improved with a complete recovery of consciousness and the disappearance of neurological defects.Examinations to determine the etiology made us hypothesize a secondary status of thrombotic thrombocytopenic purpura due to an autoimmune disorder compatible with Sjogren’s syndrome. The patient was discharged and prescribed prednisone.Currently the patient is in good clinical condition and continues the therapy with prednisone (5 mg/die.

  8. Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab.

    Science.gov (United States)

    Caramazza, Domenica; Quintini, Gerlando; Abbene, Ignazio; Malato, Alessandra; Saccullo, Giorgia; Lo Coco, Lucio; Di Trapani, Rosa; Palazzolo, Roberto; Barone, Rita; Mazzola, Giuseppina; Rizzo, Sergio; Ragonese, Paolo; Aridon, Paolo; Abbadessa, Vincenzo; Siragusa, Sergio

    2010-12-01

    Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS. This review of the literature focuses on the role of rituximab, a chimeric monoclonal antibody directed against CD20 antigen expressed by B lymphocytes, in patients with relapsing or refractory TTP-HUS with or without ADAMTS-13 deficiency, suggesting that rituximab may produce clinical remission in a significant proportion of patients. Rituximab therapy reduces plasma requirement and avoids complications related to salvage-immunosuppressive therapy. In conclusion, rituximab provides an effective, well-tolerated, and safe treatment option for patients with idiopathic TTP-HUS, thus giving an alternative approach to the current treatment based on PE.

  9. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

    Science.gov (United States)

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.

  10. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

    Directory of Open Access Journals (Sweden)

    Suella Martino

    Full Text Available Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP. Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04. Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all. Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03. Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.

  11. [Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura].

    Science.gov (United States)

    Tang, Ying; Wang, Shu-Chun; Wang, Lu-Juan; Liu, Yong; Wang, Hai-Ying; Wang, Zhan-Ju

    2013-04-01

    This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P helicobacter pylori group was higher than that in the single drug group (P helicobacter pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children.

  12. Research on persistent and chronic immune thrombocytopenia%持续性和慢性免疫性血小板减少症的临床研究

    Institute of Scientific and Technical Information of China (English)

    戴蕾莲; 宪莹; 苏庸春; 肖剑文; 温贤浩; 管贤敏; 于洁

    2012-01-01

    Objective To analyze the clinical features and therapeutic effect of the patients with persistent immune thrombocytopenia (pITP) and chronic immune thrombocytopenia (cITP). Methods One hundred and three patients with pITP and cITP were recruited in this study. The gender, age, risk factors, virus infection, bleeding, platelet counts, the treatment, and the therapeutic effect were analyzed and evaluated. The statistical software SPSS 13.0 was used to analyze the data. Results (1) Ninety nine patients (96. 1%) were more than 3 years old; the ratio of males to females was 1. 24 : 1. (2)76 (73.8%) patients was complicated with apparent risk factors, among which, 68 (89.5%) had upper respiratory infection; the positive rate of viral serum antigen IgM was 45. 0% ( n = 36) , and the mixed infection rate was 36. 1% (n = 13 ). (3) 63 patients (61. 2% ) were complicated with mucosal bleeding, and 26 patients (25.2%) with hemorrhagic anemia (mainly mild anemia); 73 patients (70.9%) had platelet counts less than 25 X 10 /L; there was no relationship between thrombocytopenia and bleedings or anemia degree. (4)61 patients (59. 2% ) reveived maintenance therapy; the incidence of mucosal bleeding in these patients ( 55. 7% , n = 34 ) was lower than those with intermittent therapy ( 69. 0% , n = 29 ) ; besides, the incidence of hemorrhagic anemia in these patients (8.2% , n =5) was lower than those with intermittent therapy ( 50. 0% , n = 21) (x2 = 23. 034, P 0.05).(4)遵医嘱维持用药治疗者占59.2%,该组患儿黏膜出血的发生率(55.7%)低于维持间断治疗组(69.0%);而维持用药组患儿失血性贫血发生率(8.2%)显著低于间断治疗组(50.0%),差异有极显著性(χ2=23.034,P<0.001).(5)单用激素组(79.7%)、激素+IVIG(静脉注射用人免疫球蛋白)组(78.6%)治疗有效率高于激素+VCR(长春新碱)组(40.0%);激素+IVIG与激素+VCR组间疗效差异有显著性(χ2=4.441,P=0.035);单用激素组与激素+VCR组间疗效

  13. Mechanisms regulating skin immunity and inflammation.

    Science.gov (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

    2014-05-01

    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  14. Innate Immunity and Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Abhishek Shastri

    2013-01-01

    Full Text Available Inflammation of central nervous system (CNS is usually associated with trauma and infection. Neuroinflammation occurs in close relation to trauma, infection, and neurodegenerative diseases. Low-level neuroinflammation is considered to have beneficial effects whereas chronic neuroinflammation can be harmful. Innate immune system consisting of pattern-recognition receptors, macrophages, and complement system plays a key role in CNS homeostasis following injury and infection. Here, we discuss how innate immune components can also contribute to neuroinflammation and neurodegeneration.

  15. Innate immunity and neuroinflammation.

    Science.gov (United States)

    Shastri, Abhishek; Bonifati, Domenico Marco; Kishore, Uday

    2013-01-01

    Inflammation of central nervous system (CNS) is usually associated with trauma and infection. Neuroinflammation occurs in close relation to trauma, infection, and neurodegenerative diseases. Low-level neuroinflammation is considered to have beneficial effects whereas chronic neuroinflammation can be harmful. Innate immune system consisting of pattern-recognition receptors, macrophages, and complement system plays a key role in CNS homeostasis following injury and infection. Here, we discuss how innate immune components can also contribute to neuroinflammation and neurodegeneration.

  16. Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    高维强; 苏健; 白霞; 王兆钺; 阮长耿

    2004-01-01

    Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83±19.98)%, P<0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P<0.03 and P<0.001, respectively), they were relatively high in comparison with that of TTP patients (P<0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

  17. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

    DEFF Research Database (Denmark)

    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a p...

  18. Expression of immune autoantibodies in children with persistent/chronic immune thrombocytopenia%持续性和慢性免疫性血小板减少症患儿免疫抗体表达的意义

    Institute of Scientific and Technical Information of China (English)

    李珊珊; 蒋慧; 夏敏

    2015-01-01

    Objective To investigate the expression and clinical significance of platelet autoantibodies in children with persistent/chronic immune thrombocytopenia (pITP/cITP).Methods Total of 34 children diagnosed with pITP/cITP(14 cases and 20 cases,respectively)in the Department of Hematology and Oncology,Shanghai Children's Hospital from December 2013 to August 2014 were enrolled as the study group,including 20 male and 14 female,the median age of 5 years old.The study also included 20 healthy children (the healthy control group) matched with gender and age,and 24 cases of newly diagnosed ITP (newly diagnosed ITP group) serving as the control groups.Platelet-associated immunoglobulin (PAIg) and platelet-specific autoantibodies on surface of platelets were mea-sured by flow cytometry or flow cytometric bead.Results Significant elevation of PAIgA,PAIgM,PAIgD and specific autoantibodies against glucoprotein(GP) Ⅲa,and GP Ⅱb were demonstrated in children with cITP,as well as specific autoantibodies against GP Ⅰ b,GP Ⅲ a,GP Ⅱ b,and granule membrane protein 140 (GMP140) in children with pITP,compared with the healthy control group(P < 0.05);the levels of GPⅨ,GP Ⅲ a,GMP140 in cITP group and GP Ⅱ b in pITP showed significant declination,compared with the newly diagnosed ITP group(P < 0.05);between piTP group and cITP group,autoantibodies GPⅨ,GP Ⅰ b,GP Ⅱ b,and GMP140 in the latter were much lower(P < 0.05).Significant negative relation between PAIgM and platelet count was found in cITP group (P < 0.05).Receiver operating characte-ristic (ROC) curve analysis showed that the area under ROC curve (AUC) of GP Ⅲ a autoantibodies was larger than that of other platelet-autoantibodies in pITP/ciTP diagnosis.Conclusions Platelet autoantibodies play a significant role in pITP/ciTP,especially platelet-specific autoantibodies,which show a declining tendency in the course and may be the main mechanism.The detection of GPⅢa specific autoantibody is more

  19. Influence of a chronic {sup 90}Sr contamination by ingestion on the hematopoietic, immune and bone systems; Influence d'une contamination chronique par ingestion de {sup 90}Sr sur les systemes hematopoietique, immunitaire et osseux

    Energy Technology Data Exchange (ETDEWEB)

    Synhaeve, Nicholas

    2011-12-15

    Strontium 90 ({sup 90}Sr) is a radionuclide of anthropogenic origin released in large quantities in the environment as a result of nuclear atmospheric tests or accidents at nuclear facilities. {sup 90}Sr persists on a long-term basis in the environment, leading to chronic contamination by ingestion of populations living on contaminated territories. The induction of bone tumours associated with the fixation of {sup 90}Sr has been widely described. However, the occurrence of non-cancer effects is much less known. We used a mouse model with chronic contamination by ingestion of water containing 20 kBq/l of {sup 90}Sr. A bio-kinetic study confirmed the accumulation of {sup 90}Sr in the bones, with an increased rate of accumulation during bone growth. This accumulation was higher in the bones of females than in males. The whole-body absorbed doses ranged from 0.33 {+-} 0.06 mGy (birth) to 10.6 {+-} 0.1 mGy (20 weeks). The absorbed dose for the skeleton was up to 55 mGy. Ingestion of {sup 90}Sr induced a change in the expression of genes inducing an imbalance in favour of bone resorption, but without effect on bone morphology. No significant effect was observed for the hematopoietic system. On the other hand, minor modifications were observed for the immune system. To evaluate the functionality of the immune system, a vaccination test with TT and KLH antigens was used. Results showed in contaminated animals a significant decrease in the production of specific immunoglobulins, changes in the Th1/Th2 balance in the spleen and a disrupted B lymphocyte differentiation. These results improve the understanding of some of the noncancerous consequences of chronic exposure at low dose of radionuclides with a long half-life, which can be accidentally released. (author)

  20. Treatment of 37 Patients with Refractory Idiopathic Thrombocytopenic Purpura by Shengxueling(升血灵)

    Institute of Scientific and Technical Information of China (English)

    SHAO Ke-ding; ZHOU Yu-hong; SHEN Yi-ping; YE Bao-dong; GAO Rui-lan; ZHANG Yu

    2007-01-01

    Objective:To explore the clinical effect and possible mechanism of Shengxueling(升血灵,SXL),a Chinese medical preparation mainly consisting of ginseng saponins,in treating refractory idiopathic thrombocytopenic purpura(ITP).Methods:The selected 69 patients with ITP were randomly assigned to two groups,the 37 patients in the treated group were treated orally by SXL with the dose for adult as 60 mg twice a day for two weeks.Then when no marked rise of platelet count after that,the dose would be doubled and administered for another two weeks.Then the dose could be gradually reduced to the initiative level in patients who responded to the treatment,and if they did not,the treatment was regarded as ineffective and be terminated.The 32 patients in the control group were treated with ampeptide elemente instead of SXL,0.4 g each time three times a day in the first two weeks,and,if that was ineffective,0.2 g would be added each time and 1.8 g would be administered a day for two more weeks.Four weeks' treatment was regarded as one therapeutic course for both groups and the observation lasted for two successive courses in patients showing positive response.Results:In the 37 patients in the treated group,markedly effective was obtained in 7(19.0%),favorably effective in 15(40.5%),improved in 5(13.5%) and ineffective in 10(27.0%),the total effective rate being 59.5%.The corresponding number in the 32 patients in the control group was 4(12.5%),6(18.8%),3(9.4%),19(59.4%)and 31.3% respectively.Comparison showed the difference in therapeutic efficacy between the two groups was significant(P<0.05).Conclusion:SXL is a safe and effective preparation for treatment of ITP,showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.

  1. Immunity to Diphtheria in Haemodialysis Patients

    OpenAIRE

    Abdolreza S. Jahromi; Mortaza Pourahmd; Sara Azhdari; Gita Manshoori; Abdolhossain Madani; Seyed H. Moosavy

    2011-01-01

    Problem statement: The incidence of infectious diseases is increased in patients with chronic renal failure. Chronic renal failure severely influences the immune functions of the host. Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. Approach: To evaluate the anti-Diphtheria immunity level in southern Iranian patients ...

  2. Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

    DEFF Research Database (Denmark)

    Kloverpris, Henrik; Karlsson, Ingrid; Bonde, Jesper

    2009-01-01

    . RESULTS:: Previously undetected T-cell responses specific for one or more epitopes were induced in all 12 individuals. Half of the participants had sustained CD4 T-cell responses 32 weeks after immunization. No severe adverse effects were observed. No overall or sustained change in viral load or CD4 T...... with seven CD8 T-cell epitopes and three CD4 T-cell epitopes. Epitope-specific responses were evaluated by intracellular cytokine staining for interferon-gamma, tumor necrosis factor alpha and interleukin-2 and/or pentamer labeling 3 weeks prior to, 10 weeks after and 32 weeks after the first immunization......-cell counts was observed. CONCLUSION:: These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could...

  3. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N

    1995-01-01

    stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated...... to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival...

  4. Traditional Chinese Medicine for Chronic Nephritis Patients and Effects on Immune Function Influence%中医药对慢性肾炎患者免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    左琪

    2012-01-01

    Chronic glomerulonephritis ( CGN ) is a common clinical kidney disease, by a variety of reasons, a variety of histologic type of primary glomerular consisting of a group of autoimmune diseases. According to their histologic type and stage of the disease, the clinical presentation varies diversification performances. Recently some scholars used traditional Chinese medicine in patients with chronic nephritis immune function, thereby improving the clinical curative effect of chronic nephritis, delaying its development process and has made gratifying progress.%慢性肾小球肾炎(CGN)是临床常见的肾脏疾病,由多种原因、多种病理类型组成的原发于肾小球的一组免疫性疾病.根据其病理类型和病期不同,临床表现各不相同,呈多样化表现.近期有学者采用中医药调节慢性肾炎患者的免疫功能,从而提高慢性肾炎的临床疗效,延缓其发展进程,取得了可喜的进展.

  5. The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura

    Directory of Open Access Journals (Sweden)

    Emel Okulu

    2011-09-01

    Full Text Available Objective: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α -308 G/A and transforming growth factor-beta 1 (TGF-β1 –915 G/C polymorphisms in the development and clinical progression of childhood ITP.Materials and Methods: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms.Results: The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05. The frequency of TGF-β1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05. The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249 or TGF-β1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755 polymorphisms. Conclusion: The frequency of TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

  6. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C;

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  7. 慢性咽炎及慢性扁桃体炎的治疗%Treatment of Chronic Pharyngitis and Chronic Tonsillitis

    Institute of Scientific and Technical Information of China (English)

    李健; 吴合

    2003-01-01

    Objective To illustrate the proper treatment of chronic pharyngitis and chronic tonsilli-tis. Methods To recover the immune functions of the patients. Result Chronic pharyngitis and chronictonsillitis could be radically cured by restoring the immune functions of the patients. Conlcusion Thekey etiology of the chronic pharyngitis and chronic tonsillitis is the abnormal immune functions of the patients and the key treatment is to restore the immune functions of the patients.

  8. “Ninjinto” (Ginseng Decoction, a Traditional Japanese Herbal Medicine, Improves Gastrointestinal Symptoms and Immune Competence in Patients with Chronic Intestinal Failure

    Directory of Open Access Journals (Sweden)

    Shuichiro Uehara

    2015-01-01

    Full Text Available Background. Treating functional gastrointestinal disorders is extremely difficult. We herein report the effect of the oral administration of Ninjinto (NJT, ginseng decoction, a traditional Japanese Kampo medicine, on chronic intestinal failure. Patients and Methods. Seven patients with chronic intestinal failure treated with NJT were evaluated in this study. The primary diseases included chronic intestinal pseudoobstruction (CIPO: n=4, short bowel syndrome (SBS: n=2, and intestinal atresia n=1. All patients orally received NJT extract granules at a dose of 0.3 g/kg BW per day. The treatment outcomes were then assessed according to the patients’ symptoms and consecutive abdominal X-ray findings. Results. The targeted symptoms were abdominal distension in four patients, diarrhea in three patients, and frequent hospitalization due to infections in two patients. An improvement in the symptoms was observed in six of the seven patients, whereas one patient with SBS did not show any improvement. An improvement in an abdominal roentgenogram was observed in the four patients with remarkably dilated bowel loops due to CIPO. Conclusions. NJT may be effective in controlling functional gastrointestinal disorders associated with chronic intestinal failure. The use of Kampo medicine in the field of pediatric surgery may help to improve the quality of life in children suffering from such conditions.

  9. Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users.

    Science.gov (United States)

    Kapila, Aaysha; Chhabra, Lovely; Chaubey, Vinod K; Summers, Jeffery

    2014-03-03

    We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers).

  10. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: effect of prednisone treatment.

    Science.gov (United States)

    López-Karpovitch, Xavier; Graue, Gerardo; Crespo-Solís, Erick; Piedras, Josefa

    2008-07-01

    High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.

  11. Comparison of platelet counts by sysmex XE 2100 and LH-750 with the international flow reference method in thrombocytopenic patients

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    Tina Dadu

    2013-01-01

    Full Text Available Background: There are several methods for counting platelets, of which the international flow reference method (IRM is considered to be the gold standard. We compared the platelet count given by this method to the count given by automated analyzers using other methods, such as optical fluorescence and impedance. Aims: The aim of this study is to compare the platelet counts obtained by Sysmex XE 2100 by Impedance (Sysmex-I, optical florescence (Sysmex-O and reported (Sysmex-R based on the switching algorithm and LH-750 by Impedance (LH-750 with the IRM in thrombocytopenic blood samples. To calculate the sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV of various technologies at the clinically relevant transfusion thresholds of 10 × 10 9 /l and 20 × 10 9 /l. Materials and Methods: A total of 118 blood samples with platelet count of <50 × 10 9 /l were selected for the study. Platelet counts of all samples were analyzed by all methods using the Sysmex analyzer, LH-750 and IRM in parallel within 6 h of collection. Statistical Analysis Used: Pearson correlation, bland Altman analysis, sensitivity and specificity, PPV and NPV. Results and Conclusions: Sysmex-R had the least Bias and 95% limits of agreement (95%LA range and thus correlated best with IRM values. LH-750 had a higher Bias compared to Sysmex-O and Sysmex-R, but a strikingly similar 95% LA ensures similar results in all three methods. In fact, in the oncology subset, it had the narrowest 95% LA, which made it the best performer in this subgroup. Of the three Sysmex results, Sysmex-I had the highest bias, widest 95% LA and highest potential risk of over transfusion. Hence, Sysmex-R and LH-750 were found to be reliable tools for estimation of platelet count in thrombocytopenic patients.

  12. Chronic hyperosmotic stress interferes with immune homeostasis in striped catfish (Pangasianodon hypophthalmus, S.) and leads to excessive inflammatory response during bacterial infection.

    Science.gov (United States)

    Schmitz, Mélodie; Douxfils, Jessica; Mandiki, Syaghalirwa N M; Morana, Cédric; Baekelandt, Sébastien; Kestemont, Patrick

    2016-08-01

    Hyperosmotic stress has often been investigated from osmoregulation perspectives while the effects of such stress on the immune capacity remain largely unexplored. In this study, striped catfish were submitted to three salinity profiles (freshwater, low saline water, saline water) during 20 days, followed by infection with a virulent bacteria, Edwardsiella ictaluri, responsible for the enteric septicaemia of catfish. Osmoregulatory (plasma osmolality, gill Na(+)K(+)ATPase), immune (blood cells, lysozyme activity, complement activity, respiratory burst) parameters and mortality rate were investigated. In addition, abundances of heat shock protein 70 and high mobility group box 1 were explored. With elevated salinity, plasma osmolality severely increased while gill Na(+)K(+)ATPase slightly increased. Salinity alone stimulated the number of granulocytes, lysozyme activity and respiratory burst but depleted the number of thrombocytes. Salinity in combination with infection stimulated the number of monocytes and ACH50. On the contrary, erythrocytes, hematocrit, heat shock protein 70 and high mobility group box 1 did not significantly vary with salinity profiles. Then, salinity induced earlier onset on mortalities after E. ictaluri inoculation whereas cumulative mortality reach 79.2%, 67.0% and 91.7% respectively in freshwater, low saline water and saline water. In conclusion, salinity stimulates several immune functions in striped catfish but prolonged exposure to excessive hyperosmotic condition may lead to excessive inflammatory response and death.

  13. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... alcohol abuse over many years. Repeated episodes of acute ... chronic pancreatitis. Genetics may be a factor in some cases. ...

  14. 特发性血小板减少性紫癜患儿病原感染的临床分析%Clinical analysis of pathogen infection in children with idiopathic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    王晓格; 胡姬婷

    2014-01-01

    目的:探讨特发性血小板减少性紫癜(ITP)患儿与病原感染的关系。方法:回顾性分析89例ITP患儿发病的诱因,应用ELISA法检测巨细胞病毒、EB病毒、幽门螺杆菌(Hp)、支原体,并分析与ITP的关系。结果:89例ITP患儿中,46.1%的患儿发病前1~3周有病毒感染,17.9%的患儿在发病前曾有预防接种史。其中 CMV 阳性10例(11.24%),EB 病毒阳性7例(7.86%),Hp 阳性12例(13.48%),MP 阳性2例(2.25%),总阳性率30.34%(27/89)。发病时血小板计数及治疗后血小板升至正常的时间在病原阳性组与阴性组比较,差异无统计学意义(P>0.5)。经过随访,急性转为慢性 ITP 4例(4.49%),各病原阳性组总的转慢率7.40%,病原阴性组转慢率3.22%,两组比较差异有统计学意义(P<0.05)。结论:病原感染是特发性血小板减少性紫癜发病的一个重要原因,其中以HP感染所占比例较高,Hp感染组ITP患儿易迁延不愈转为慢性。%Objective:To explore the relationship between pathogen infection and children with idiopathic thrombocytopenic purpura(ITP).Methods:Cause of the disease of 89 children with ITP were retrospectively analyzed.Cytomegalovirus,EB virus, helicobacter pylori,mycoplasma were detected using ELISA method.We analyzed the relationship between them and ITP.Results:In the 89 children with ITP,46.1% children were infected by virus in 1 to 3 weeks before the onset of disease,17.9% children had vaccination history before the onset of disease.The CMV was positive in 10 cases(11.24%),EB was positive in 7 cases(7.86%),HP was positive in 12 cases(13.48%),MP was positive in 2 cases(2.25%).The total positive rate was 30.34%(27/89).The platelet count at the time of onset and platelet rose to normal time after treatment between pathogen positive group and negative group were compared.There were no statistical significance(P>0.5).At follow-up,4 patients with acute ITP turned to chronic ITP(4.49%).In

  15. The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization.

    Science.gov (United States)

    Andrew, Dean W; Cochrane, Melanie; Schripsema, Justin H; Ramsey, Kyle H; Dando, Samantha J; O'Meara, Connor P; Timms, Peter; Beagley, Kenneth W

    2013-01-01

    IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarumMajor Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however

  16. The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization.

    Directory of Open Access Journals (Sweden)

    Dean W Andrew

    Full Text Available IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i the course of natural genital tract C. muridarum infection, (ii the development of oviduct pathology and (iii the development of vaccine-induced immunity against infection in wild type (WT BALB/c and IL-17 knockout mice (IL-17-/- to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarumMajor Outer Membrane Protein (MOMP and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated

  17. Staphylococcus aureus septicemia presenting as disseminated intravascular coagulation - thrombotic thrombocytopenic purpura overlap and thrombus in inferior vena cava, right atrium and right ventricle: a case report

    Directory of Open Access Journals (Sweden)

    Khwaja Saifullah Zafar

    2015-01-01

    Full Text Available Staphylococcal sepsis following furunculosis and complicated by suspected deep vein thrombosis and septic inferior vena caval, right atrium, right ventricle emboli accompanied by disseminated intravascular coagulation (DIC - thrombotic thrombocytopenic overlap in a 65 years old lady is presented. She was managed successfully with antibiotics and anticoagulation. The case is reported for its rarity and brings to light the vivid manifestations of septicemia specially staphylococcal. [Int J Res Med Sci 2015; 3(1.000: 368-372

  18. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  19. Sub-chronic effects of nitrate in drinking water on red-legged partridge (Alectoris rufa): oxidative stress and T-cell mediated immune function.

    Science.gov (United States)

    Rodríguez-Estival, Jaime; Martínez-Haro, Mónica; Martín-Hernando, M A Paz; Mateo, Rafael

    2010-07-01

    In order to evaluate the effects of nitrates on birds, we have exposed captive red-legged partridges to nitrates concentrations of 0 (control), 100 (dwell water in farming areas) or 500 mg/l (fertirrigation level). The cellular immune response, plasma biochemistry, methemoglobin concentration (metHb), and oxidative stress biomarkers in blood and tissues were studied after two weeks of exposure. Several blood parameters such as aspartate aminotransferase, creatinine phosphokinase and lactate dehydrogenase activities and magnesium level decreased with nitrate exposure, whereas alkaline phosphatase activity and creatinine level increased. The oxidant effect of nitrates was evidenced by the increase in blood metHb, accompanied by the lipid peroxidation of red blood cells, the increased levels of oxidized glutathione (GSH) in liver, and the generation of oxidative DNA damage in plasma lymphocytes. GSH in erythrocytes was negatively correlated with blood metHb. The cellular immune function was slightly lower at partridges exposed to nitrates. These results suggest that adverse effects of nitrates on birds occur at concentrations potentially present in the field.

  20. Immune response

    Science.gov (United States)

    ... and tetanus antitoxin are examples of passive immunization. BLOOD COMPONENTS The immune system includes certain types of white ... lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that ...

  1. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO Support an Interleukin-17 Immune Response.

    Directory of Open Access Journals (Sweden)

    Alexandra Korn

    Full Text Available Recurrent airway obstruction (RAO is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17. We examined global gene expression profiles in mediastinal (pulmonary-draining lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1 and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

  2. 慢性酒精中毒性肌病伴随免疫状态变化的实验研究%Immune function study of chronic alcoholic myopathy

    Institute of Scientific and Technical Information of China (English)

    程学英; 刘奔; 钟丽珍; 赵华; 刘艳丽; 张大伟; 王剑锋

    2013-01-01

    Objective To study the relationship between chronic alcoholic myopathy and immune function . Methods SD rats chronic alcoholic myopathy model were constructed . A control group SD rats were studied at the same time . The two groups of rats were injected with ovalbumin antigen. The anti - ovatbumin antibody was detected with ELISA method. At the same time, CD19 positive B cell percentage was detected with flow cytometry . Results At the end of the modeling the body weight of the experimental group was decrease compared with the control group . The difference was significant (P <0.05)between the two groups. HE staining and transmission electron microscopy results showed that type II muscle fibers of plantaris in the experimental group rats typically changed as the chronic alcoholtoxic myopathy . When the chronic alcoholic myopathy occurs , the antibody titer of anti — ovalbumin continued to decline. In seven control point, there were significant differences (P <0. 05 ) compared with the control group .At the same time , the percentage of CD 19 positive B cell was also reduced. The difference was significant ( P < 0 05 ) between the two group rats. Conclusion When chronic alcoholic myopathy happens , the percentage of B cell is decline , the humoral immunity function will be affected at the same time.%目的通过对慢性酒精中毒性肌病大鼠模型的免疫功能变化研究,探讨慢性酒精中毒性肌病发生时机体免疫功能的状态.方法 构建SD大鼠慢性酒精中毒性肌病模型,同时设立对照组,对两组大鼠进行卵清蛋白抗原注射免疫,用ELISA法连续检测大鼠血清抗卵清蛋白抗体的变化,同时用流式细胞仪检测两组大鼠CD19阳性B细胞百分率.结果 造模完成时,实验组大鼠体重与对照组相比,差异有显著性意义(P<0.05),HE染色与透射电镜结果显示实验组大鼠跖肌II型肌纤维受累明显,呈现慢性酒精中毒性肌病典型变化.随着慢

  3. Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response

    DEFF Research Database (Denmark)

    Ciofu, Oana

    2003-01-01

    of this therapeutic strategy and our results showed the development of resistance of P. aeruginosa to several antibiotics during 25 years of intensive antibiotic treatment. Our studies have been concentrating on the development of resistance to beta-lactam antibiotics. We have shown an association between...... the development of resistance to beta-lactam antibiotics and the occurrence of high beta-lactamase producing strains and between the MIC of the beta-lactams and the levels of beta-lactamase expression. Partially derepressed mutants, characterized by high basal levels of beta-lactamase with the possibility...... of induction to even higher levels during treatment with beta-lactam antibiotics, were the most frequent phenotype found among resistant Danish P. aeruginosa CF isolates. We have also shown that the high alginate producing P. aeruginosa isolates, that characterize the chronic lung infection in CF patients...

  4. 免疫学应答与慢性乙型肝炎血清学转换的关系%The relationship between immune response and chronic hepatitis B seroconversion

    Institute of Scientific and Technical Information of China (English)

    李智彬; 刘永明; 苏何玲; 钟彦伟

    2013-01-01

    乙型肝炎病毒(HBV)感染是全球性的卫生问题,每年有将近100万人死于HBV感染所致的肝衰竭等肝脏疾病。大部分的慢性乙型肝炎(CHB)患者经过抗病毒治疗后可以达到持久的免疫,小部分的还可以达到临床治愈。理想的抗病毒治疗过程一般经过三个重要转折点,分别是 HBV DNA 转阴, HBeAg血清学转换及HBsAg血清学转换。长效干扰素治疗的患者只有40%左右的患者出现HbeAg血清学转化,因此,对CHB患者或许可采取调整患者免疫功能从而达到临床治愈。%HBV infection is a global healthy question. Every year almost one million people are dead from HBV related diseases, such as hepatic failure or liver cirrhosis. The majority of the chronic hepatitis B (CHB) patients, who had received antiviral therapy, will get the ability of antiviral persistence immunity while the minority of these patients came up to the standard of clinical cure. The ideal process of antiviral therapy has three important turning points, including HBV DNA seroconversion, HBeAg seroconversion and HBsAg seroconversion. However, only 40%patients who received pegylated interferon therapy have the effect of HBeAg seroconversion. Thus, the CHB patients may achieve clinical cure by regulating their immune functions.

  5. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS).

    Science.gov (United States)

    Neunert, Cindy E; Buchanan, George R; Imbach, Paul; Bolton-Maggs, Paula H B; Bennett, Carolyn M; Neufeld, Ellis; Vesely, Sara K; Adix, Leah; Blanchette, Victor S; Kühne, Thomas

    2013-05-30

    Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that the majority undergo remission and severe thrombocytopenia is infrequent. Details regarding bleeding manifestations, however, remain poorly categorized. We report here long-term data from the Intercontinental Cooperative ITP Study Group Registry II focusing on natural history, bleeding manifestations, and management. Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24 months thereafter. Median platelet counts were 214 × 10(9)/L (interquartile range [IQR] 227, range 1-748), 211 × 10(9)/L (IQR 192, range 1-594), and 215 × 10(9)/L (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet count <20 × 10(9)/L was uncommon (7%, 7%, and 4%, respectively). Remission occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12 months, and 24% between 12 and 24 months. There were no reports of intracranial hemorrhage, and the most common site of bleeding was skin. In patients with severe thrombocytopenia we observed a trend toward more drug treatment with increasing number of bleeding sites. Our data support that ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare.

  6. Effects of chronic exposure to sublethal concentrations of lead acetate on heme synthesis and immune function in red-tailed hawks.

    Science.gov (United States)

    Redig, P T; Lawler, E M; Schwartz, S; Dunnette, J L; Stephenson, B; Duke, G E

    1991-07-01

    Red-tailed hawks were exposed to sublethal levels of lead acetate for periods of 3 or 11 weeks. Alterations in the heme biosynthetic pathway were demonstrated after the first week of exposure to 0.82 mg lead per kilogram body weight per day. Activity of erythrocyte porphobilinogen synthase (aminolevulinic acid dehydratase) was depressed significantly and did not return to normal levels until 5 weeks after the termination of lead treatments. A rapid and relatively brief increase in erythrocyte free protoporphyrin and a slower but more prolonged increase in its zinc complex were also demonstrated with exposure to this dose of lead for 3 weeks. Less substantial decreases in hematocrit and hemoglobin levels occurred but only in the longer experiment with exposure to higher lead levels. Short term, low level lead exposure did not effect immune function significantly in the hawks, as measured by antibody titers to foreign red blood cells or by the mitogenic stimulation of T-lymphocytes. Increased lead exposure produced a significant decrease in the mitogenic response but had no effect on antibody titers.

  7. Chronic exposure of tilapia (Oreochromis niloticus) to iron oxide nanoparticles: Effects of particle morphology on accumulation, elimination, hematology and immune responses.

    Science.gov (United States)

    Ates, Mehmet; Demir, Veysel; Arslan, Zikri; Kaya, Hasan; Yılmaz, Sevdan; Camas, Mustafa

    2016-08-01

    Effects of chronic exposure to alpha and gamma iron oxide nanoparticles (α-Fe2O3 and γ-Fe2O3 NPs) were investigated through exposure of tilapia (Oreochromis niloticus) to 0.1, 0.5 and 1.0mg/L (9.2×10(-4), 4.6×10(-3) and 9.2×10(-3)mM) aqueous suspensions for 60days. Fish were then transferred to NP-free freshwater and allowed to eliminate ingested NPs for 30days. The organs, including gills, liver, kidney, intestine, brain, spleen, and muscle tissue of the fish were analyzed to determine the accumulation, physiological distribution and elimination of the Fe2O3 NPs. Largest accumulation occurred in spleen followed by intestine, kidney, liver, gills, brain and muscle tissue. Fish exposed to γ-Fe2O3 NPs possessed significantly higher Fe in all organs. Accumulation in spleen was fast and independent of NP concentration reaching to maximum levels by the end of the first sampling period (30th day). Dissolved Fe levels in water were very negligible ranging at 4-6μg/L for α-Fe2O3 and 17-21μg/L for γ-Fe2O3 NPs (for 1mg/L suspensions). Despite that, Fe levels in gills and brain reflect more dissolved Fe accumulation from metastable γ-Fe2O3 polymorph. Ingested NPs cleared from the organs completely within 30-day elimination period, except the liver and spleen. Liver contained about 31% of α- and 46% of γ-Fe2O3, while spleen retained about 62% of α- and 35% of the γ-polymorph. No significant disturbances were observed in hematological parameters, including hemoglobin, hematocrit, red blood cell and white blood cell counts (p>0.05). Serum glucose (GLU) levels decreased in treatments exposed to 1.0mg/L of γ-Fe2O3 NPs at day 30 (p0.05), but increased significantly within elimination period due to mobilization of ingested NPs from liver and spleen to blood. Though respiratory burst activity was not affected (p>0.05), lysozyme activity (LA) was suppressed suggesting an immunosuppressive effects from both Fe2O3 NPs (pniloticus under chronic exposure.

  8. Immune pathogenesy of chronic obstructive pulmonary disease with respiratory syncytial virus infection%呼吸道合胞病毒感染与慢性阻塞性肺疾病发病的免疫机制

    Institute of Scientific and Technical Information of China (English)

    马冠华; 杨昆; 李敏

    2009-01-01

    慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种常见的呼吸系统疾病.随着近年来对病毒导致慢性阻塞性肺疾病急性加重(AECOPD)机制的深入研究以及呼吸道病毒检出率的提高,病毒感染在COPD发病机制中的作用受到了更多关注.呼吸道合胞病毒(respiratory syncytial vius,RSV)是常见的呼吸道病毒.有关RSV与宿主的免疫学的研究提示了COPD中RSV的易感性,可能成为某些COPD患者防治疾病发展的新方向.本文对病毒感染在AECOPD中的作用以及RSV感染与COPD发病机制的免疫研究进展现状作一综述.%Chronic obstructive pulmonary disease(COPD)is a kind of common disease in respiratory system.With the recent advances in virus-induced acute exacerbations and elevated detection rates of viruses,the etiological status of virus in COPD is getting more attention.Respiratory syncytial virus is a common respiratory virus,some researchers suggest susceptibility of RSV to COPD,which may suggest prospective prevention and therapy to certain kind of COPD patients.This article summarizes the function of virus infection in acute exacerbation COPD and makes a review of the update on the immune pathogenesy of COPD with RSV infection.

  9. Proteome profiles of HDL particles of patients with chronic heart failure are associated with immune response and also include bacteria proteins.

    Science.gov (United States)

    Oberbach, Andreas; Adams, Volker; Schlichting, Nadine; Heinrich, Marco; Kullnick, Yvonne; Lehmann, Stefanie; Lehmann, Sven; Feder, Stefan; Correia, Joao Carlos; Mohr, Friedrich-Wilhelm; Völker, Uwe; Jehmlich, Nico

    2016-01-30

    Besides modulation of reverse cholesterol transport, high density lipoprotein (HDL) is able to modulate vascular function by stimulating endothelial nitric oxide synthase. Recently, it could be documented that this function of HDL was significantly impaired in patients with chronic heart failure (CHF). We investigated alterations in the HDL proteome in CHF patients. Therefore, HDL was isolated from 5 controls (HDLhealthy) and 5 CHF patients of NYHA-class IIIb (HDLCHF). Proteome analysis of HDL particles was performed by two-dimensional liquid chromatography-mass spectrometry (SCX/RP LC-MS/MS). In total, we identified 494 distinct proteins, of which 107 proteins were commonly found in both groups (HDLCHF and HDLhealthy) indicating a high inter-subject variability across HDL particles. Several important proteins (e.g. ITGA2, APBA1 or A2M) varied in level. Functional analysis revealed regulated pathways. A minor proportion of bacteria-derived proteins were also identified in the HDL-particles. The extension of the list of HDL-associated proteins allows besides their mere description new insights into alterations in HDL function in diseases. In addition, the detection of bacterial proteins bound to HDL will broaden our view of HDL not only as a cholesterol carrier but also as a carrier of proteins.

  10. 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 low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

  11. Mathematical models for the study of the dynamics of indium-111-labelled platelets in idiopathic thrombocytopenic purpura

    Energy Technology Data Exchange (ETDEWEB)

    Savolainen, S.

    1992-01-01

    Platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP) was investigated by applying various models (compartmental and open models, and functional and uptake analyses) to data on indium-111 labelled platelets monitored with a gamma camera following intravenous injection of labelled platelets. The usefulness of the selected models was tested by relating kinetic data to pathophysiological phenomena. A comparison of the results of platelet and colloid kinetics showed that the splenic platelet kinetics in ITP patients does not seem to be primarily dependent on the reticuloendothelial system. Although closed three-compartmental analysis seemed to be superior to the other models applied, none of the methods of analysis tested in this study appears to provide a complete description of short-lived platelet dynamics, as for every model certain assumptions that are not entirely relevant have to be made; this stresses the importance of combining various methods for a comprehensive analysis of a complex phenomenon. Conclusions concerning the function of biological systems should be based on more than one dynamic model or calculation method, since applying only one model (or calculation method) may give artifactual results due to poor statistics of observed data or to inexactness of the assumptions concerning the model.

  12. Thrombotic Thrombocytopenic Purpura:Clinical Analysis of 12 Cases%血栓性血小板减少性紫癜12例临床分析

    Institute of Scientific and Technical Information of China (English)

    刘景华; 周凡; 刘彦琴; 王吉刚; 白颖; 刘洋; 惠玉; 张晓琳; 李敏燕

    2014-01-01

    目的:总结分析血栓性血小板减少性紫癜患者的临床表现,实验室特点及治疗,以提高对血栓性血小板减少性紫癜的诊断及治疗水平。方法回顾性分析我院2008年1月~2013年12月诊断的12例血栓性血小板减少性紫癜患者的临床表现、实验室检查及治疗方法。结果①12例患者表现为五联征(微血管病性溶血性贫血、血小板减少、神经精神症状、发热、肾脏损害)者8例,三联征(微血管病性溶血性贫血、血小板减少、神经精神症状)者11例。②所有患者乳酸脱氢酶水平均增高,外周血破碎红细胞比例2~15%。③原发病:病因淋巴瘤1例,抗磷脂抗体综合征LPS 1例,系统性红斑狼疮SLE 1例,免疫因素5例,感染2例,原因不明2例。④治疗以血浆置换、血浆输注、利妥昔单抗、糖皮质激素为主,治疗有效率82.7%。结论血栓性血小板减少性紫癜的早期诊断仍然依赖临床表现,在进行血浆置换、利妥昔单抗等抢先治疗的同时完善相关检查进行排除性诊断。%Objective To investigate clinical features,outcome and laboratory characteristics of thrombotic thrombocytopenic purpura (TTP) and improve diagnostic ability for physician in TTP management. Methods Totally 12 diagnosed TTP from 2008.1 to 2013.12 were analyzed clinical features, laboratory characteristics and treatment. Results ①There were 8 patients with the pentad of TTP,including hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and kidney injury. 11 patients had triad of TTP. ②Al the patients had high level of lactate dehydrogenase, and the schistocytes of peripheral blood smears were present in al cases with a arrange of 2%~15%. The primary disease: 1 cases of lymphoma, antiphospholipid antibody syndrome and 1 cases of LPS, 1 cases of systemic lupus erythematosus SLE, immune factors in 5 cases, infection in 2 cases, 2 cases with unknown causes

  13. Mathematical Modelling of Immune Response in Tissues

    Directory of Open Access Journals (Sweden)

    B. Su

    2009-01-01

    Full Text Available We have developed a spatial–temporal mathematical model (PDE to capture fundamental aspects of the immune response to antigen. We have considered terms that broadly describe intercellular communication, cell movement, and effector function (activation or inhibition. The PDE model is robust to variation in antigen load and it can account for (1 antigen recognition, (2 an innate immune response, (3 an adaptive immune response, (4 the elimination of antigen and subsequent resolution of the immune response or (5 equilibrium of the immune response to the presence of persistent antigen (chronic infection and the formation of a granuloma.

  14. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study

    Directory of Open Access Journals (Sweden)

    Lesuis Nienke

    2012-08-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA, inflammatory bowel disease (IBD, and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed. Methods Data on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women. Results In total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis. Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse scores for objective disease activity measures. A similar trend to RA was seen in IBD

  15. Interactions between the immune and nervous systems in pain

    OpenAIRE

    Ren,Ke; Dubner, Ronald

    2010-01-01

    Immune cells and glia interact with neurons to alter pain sensitivity and to mediate the transition from acute to chronic pain. In response to injury, resident immune cells are activated and blood-borne immune cells are recruited to the site of injury. Immune cells not only contribute to immune protection but also initiate the sensitization of peripheral nociceptors. Through the synthesis and release of inflammatory mediators and interactions with neurotransmitters and their receptors, the im...

  16. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.

    2013-01-01

    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  17. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  18. Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is the answer

    Directory of Open Access Journals (Sweden)

    Prashant Nasa

    2011-01-01

    Full Text Available The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia-eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management.

  19. Cancer Immunity: Lessons From Infectious Diseases.

    Science.gov (United States)

    Trinchieri, Giorgio

    2015-07-15

    Innate and adaptive immunity are activated by both infections and tumors. The immune cells infiltrating infected tissues are similar to those infiltrating neoplastic tissues, but their function in the first setting is quite different from that in the latter. Infected tissues are usually characterized by an acute inflammatory environment that favors the generation of protective immunity, whereas tumors are characterized by chronic inflammation that suppresses antitumor immune responses and promotes tumor growth and escape from the immune system. During resolution of the immune response to infection or in chronic infections, immunosuppressive mechanisms that are typical of the tumor microenvironment are observed in infected tissues. Conversely, immunotherapy and chemotherapy may redirect the tumor microenvironment and allow the activation of effective anticancer immune responses. The transformation of neoplastic cells is determined by intrinsic genetic alteration but tumor progression is controlled by the tumor microenvironment and by the inflammatory and immune response to the tumors. Commensal microorganisms live in great numbers in all our barrier epithelia and control inflammation and immunity both locally and systemically. The commensal microbiota is essential for optimal immune response to pathogens and for the establishment of autoimmunity. It also modulates inflammation and immune responses that affect tumor growth and it is required for the effectiveness of anticancer immunotherapy and chemotherapy.

  20. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    Directory of Open Access Journals (Sweden)

    Khadilkar Satish

    2011-01-01

    Full Text Available The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP. Pure motor (multifocal motor neuropathy, sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy, exclusively distal sensory (distal acquired demyelinating sensory neuropathy and very proximal sensory (chronic immune sensory polyradiculopathy constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc. have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.

  1. Activation and Exhaustion of Adaptive Immune Cells in Hepatitis B Infection.

    Science.gov (United States)

    Gogoi, Dimpu; Borkakoty, Biswajyoti; Biswas, Dipankar; Mahanta, Jagadish

    2015-09-01

    In hepatitis B virus (HBV) infection, the immune reaction is responsible for viral clearance and preventing their spread within the host. However, the immune system is dysfunctional in patients with chronic HBV infection, leading to an inadequate immune response against the virus. A major factor contributing to inefficient immune function is the phenomenon of immune exhaustion. Hence, understanding immune activation and exhaustion during HBV infection is important, as it would provide insight in developing immunotherapy to control chronic HBV infection. The aim of this review is to highlight the existing information on immune effector functions and immune exhaustion in response to HBV infection.

  2. TXRF analysis of low Z elements in serum of patients with idiopathic thrombocytopenic purpura using X-ray fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Canellas, Catarine G.L.; Leitao, Roberta G.; Lopes, Ricardo T., E-mail: catarine@lin.ufrj.b, E-mail: ricardo@lin.ufrj.b [Universidade Federal do Rio de Janeiro (PEN/COPPE/UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-Graduacao de Engenharia. Lab. de Instrumentacao Nuclear; Carvalho, Silvia M.F., E-mail: silvia@hemorio.rj.gov.b [State Institute of Hematology Arthur de Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ (Brazil); Bellido, Alfredo Victor B., E-mail: alfredo@ien.gov.b [Federal Fluminense University (UFF), Niteroi, RJ (Brazil). Chemistry Inst.; Anjos, Marcelino J., E-mail: marcelin@lin.ufrj.b [State University of Rio de Janeiro (UERJ), RJ (Brazil). Physics Inst.

    2011-07-01

    Idiopathic thrombocytopenic purpura (ITP) is a blood disorder characterized by an abnormal decrease in the number of platelets in the blood. ITP results from development of an antibody directed against a structural platelet antigen (an autoantibody). Platelets are also called thrombocytes, meaning cells that form clots. The cause of ITP is not known and their diagnosis requires that other disorders be excluded through selective tests. In this work, forty patients suffering from ITP and sixty healthy volunteers (Control Group) were analyzed. All the serum samples had been collected from people who live in the urban area of Rio de Janeiro City/Brazil. Blood was collected into vacutainers without additives. The measurements were performed at the X-ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo using a monochromatic beam with maximum energy of 20 keV for the excitation and an Ultra-LEGe detector with resolution of 148 eV at 5.9 keV. Standard solutions with Vanadium as internal standard were prepared for calibration system. It was possible to determine the elemental concentrations of the following six elements: Na, P, S, Cl, K and Ca. The Student's t-test was used to analyze significant differences ({alpha} = 0.05) between group of patients with ITP and control group. The elements that presented significant differences for the mean of their concentrations between each one of the ITP group and control group in {mu}g.g-1 were: phosphorous (136{+-}12 and 92{+-}12), Sulphur (1077{+-}97 and 847{+-}80), Chlorine (2905{+-}385 and 2266{+-}378), Potassium (137{+-}118 and 82{+-}15) and Calcium (64{+-}7 and 44{+-}6) respectively. These results will help the biomedical field with regard to early diagnosis and improved medical treatment. Thus, our findings indicate that these elements can be related to the important biochemical processes in ITP. (author)

  3. FATAL OUTCOME OF INFECTION BY DENGUE 4 IN A PATIENT WITH THROMBOCYTOPENIC PURPURA AS A COMORBID CONDITION IN BRAZIL

    Directory of Open Access Journals (Sweden)

    Frederico Figueiredo Amâncio

    2014-06-01

    Full Text Available Dengue is currently a major public-health problem. Dengue virus (DENV is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions.

  4. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura

    KAUST Repository

    Lancellotti, S.

    2015-08-13

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  5. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    Energy Technology Data Exchange (ETDEWEB)

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  6. Experience of buffy coat pooling of platelets as a supportive care in thrombocytopenic dengue patients: A prospective study

    Directory of Open Access Journals (Sweden)

    Kabita Chatterjee

    2014-01-01

    Full Text Available Random donor platelet (RDP is not sufficient to improve the platelet count in most thrombocytopenic patients. Single donor platelet (SDP or buffy coat pooled platelet (BCPP are the two choices to provide a full therapeutic dose of platelets. However, there are constraints in the preparation of SDP due to stringent donor selection procedure, time required for procedure, and need of special expensive equipments and kits. BCPP is widely practiced, especially in the European countries, since 1995. In India, we decided to adopt the procedure of buffy coat pooling of platelets, especially for economically backward patients and for emergencies. This study was prospectively conducted from September 2009 to September 2010. A total of 129 units of BCPP [tested prior for viral markers by enzyme-linked immunosorbent assay (ELISA and individual donor nucleic acid amplification test (ID-NAT] were issued to 129 patients suffering from dengue and were included in this study. For comparison between efficacy of SDP and BCCP, patients were divided into two groups of 50 each. The post-transfusion platelet counts of the patients were noted after 2 hours of transfusion for each type of component. The platelet yield varied from 2.5 to 4.4 Χ 10ΉΉ in BCPP samples. The samples analyzed were sterile without any contamination. The different biochemical parameters were analyzed in detail. The observed post-transfusion platelet recovery and corrected count increment (CCI at 1 hour and 24 hours after BCPP transfusion were similar to that after SDP transfusion. Hence, we concluded that BCPP can be a low cost alternative to SDP in the times of emergencies like dengue and non-affordability by the patient for SDP.

  7. Coevolutionary immune system dynamics driving pathogen speciation.

    Directory of Open Access Journals (Sweden)

    Kimberly J Schlesinger

    Full Text Available We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.

  8. Mechanisms of LAIR-1 mediated inhibition of immune function

    NARCIS (Netherlands)

    Verbrugge, Annelies

    2005-01-01

    The mammalian immune system has to eliminate pathogens, while preventing damage to the host. An adequate function of the immune system therefore requires the coordinate action of activating and inhibitory signals. Loss of inhibitory signals may lead to chronic inflammation or auto-immune disease. A

  9. Immune Function Changes in Patients with Invasive Pulmonary Fungal Infections by Chronic Obstructive Pulmonary Disease%慢性阻塞性肺病合并肺部真菌感染免疫功能的变化

    Institute of Scientific and Technical Information of China (English)

    杨青茹; 武焱旻; 张敬浩

    2013-01-01

    目的:探讨慢性阻塞性肺病(慢阻肺)合并肺部真菌感染患者免疫功能的变化及其意义。方法对2010年1月至2012年12月在徐州市中心医院呼吸科(含呼吸ICU)住院患者中慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)合并肺部念珠菌感染患者53例及合并肺部曲霉菌感染患者25例作为研究对象,对其免疫功能进行检测,并与20名正常健康人群(健康对照组)进行对比分析。采用流式细胞仪检测周血T淋巴细胞亚群(CD3+CD4+、CD3+CD8+、CD4+/CD8+)的表达率,采用全自动蛋白分析仪检测患者血清IgM、IgG、IgA含量。结果念珠菌组和曲霉菌组的CD3+CD4+百分比及CD4+/CD8+均明显低于健康对照组(P<0.01),念珠菌组及曲霉菌组CD3+CD8+百分比高于健康对照组(P<0.05),念珠菌组的CD3+CD4+百分比及CD4+/CD8+均低于曲霉菌组(P<0.01),而CD3+CD8+百分比在曲霉菌组及念珠菌组之间无统计学差异。与健康对照组比较,念珠菌组和曲霉菌组的IgG明显低于健康对照组,(P<0.01),IgA均高于健康对照组,(P<0.05),念珠菌组的IgG高于曲霉菌组(P<0.01),而念珠菌组及曲霉菌组IgA比较及三组间IgM比较,无统计学差异。结论慢性阻塞性肺病合并肺部念珠菌及曲霉菌感染时,细胞免疫及体液免疫均受损,其中合并曲霉菌感染时的免疫受损状况较合并念珠菌感染时更重。%Objective To investigate the changes of immune function in patients with invasive pulmonary fungal infections by chronic obstructive pulmonary disease. Methods 78 patients with invasive pulmonary fungal infections by chronic obstructive pulmonary disease were slected, in which ,53 patients were pulmonary candidiasis and 25 patients were pulmonary aspergillosis. The T lymphocyte subsets in peripheral whole blood samples were derected by flow cytometry. The levels of IgM,IgG, IgA were

  10. Nursing experience of idiopathic thrombocytopenic purpura%特发性血小板减少性紫癜的护理体会

    Institute of Scientific and Technical Information of China (English)

    袁玖莲

    2015-01-01

    目的:本文通过回顾性分析56例特发性血小板减少性紫癜患者的临床资料,阐述了本病的心理护理、病情观察、出血的护理、用药护理、饮食护理、健康教育等护理措施。对特发性血小板减少性紫癜患者采取综合性的护理干预措施,可以有效地提高临床治疗效果,降低并发症的发生率,降低死亡率。%In this paper,through retrospectively analyzing the clinical datas of 56 patients with idiopathic thrombocytopenic purpura,the author expounded the mental nursing,observation,bleeding nursing,drug nursing,diet nursing and health education. Comprehensive nursing intervention measures for patients with idiopathic thrombocytopenic purpura can effectively improve the clinical treatment effect,reduce the incidence of complications and mortality.

  11. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    Directory of Open Access Journals (Sweden)

    Bonilla-Abadía Fabio

    2012-12-01

    Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  12. Shiga toxin-associated hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: distinct mechanisms of pathogenesis.

    Science.gov (United States)

    Tarr, Phillip I

    2009-02-01

    The hemolytic uremic syndrome (HUS) of childhood is, in its most common form, a non-immune microangiopathic hemolytic anemia. HUS typically follows an enteric infection with a Shiga toxin-producing Escherichia coli, usually belonging to serotype O157:H7. The antecedent infection is almost always manifested as non-bloody diarrhea. In about 80% of cases, the diarrhea becomes bloody between one and five days after the onset of diarrhea. The courses of acute gastrointestinal infections, and of HUS, in adults and children are similar. There are no convincing data that this easily recognizable form of microangiopathy is related to any inborn or acquired deficiency of ADAMTS13, and plasma therapies are not justified on either theoretical or empirical grounds. Similarly, there are no realistic animal data to support use of plasma exchange or infusion in children or adults with, or at risk for, HUS secondary to gastrointestinal infection with E. coli O157:H7. Best clinical practices involve rapid and accurate clinical and microbiological identification of infected patients, volume expansion, and support of the intestinal and extraintestinal complications that can ensue during acute enteric infection and associated HUS. Clinical clues include a sequence of events where the stool becomes bloody after a several-day interval of bloody diarrhea, considerable abdominal pain, five or more stools in the 24 h before presentation, pain on defection, and absence of fever at the time of presentation. Diagnosis should rely primarily on sorbitol MacConkey agar culture. Shiga toxin testing should not be used as the only screen to identify infected patients.

  13. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  14. Stress, depression and immunity : the role of defense and coping styles

    NARCIS (Netherlands)

    Olff, M

    1999-01-01

    It is by now widely recognized that acute and chronic stress have an impact on the immune system. Acute stress may have a stimulating effect on the immune system, while in the case of chronic stress - and in particular in depression - the immune system may be down-regulated. However, there is consid

  15. Immune disorders in hemodialysis patients.

    Science.gov (United States)

    Sharif, Mohammad Reza; Chitsazian, Zahra; Moosavian, Mehdi; Raygan, Fariba; Nikoueinejad, Hassan; Sharif, Ali Reza; Einollahi, Behzad

    2015-03-01

    Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of "dialysis syndrome" (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual's repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients.   This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.

  16. Innate immune recognition of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Hong-Yan; Liu; Xiao-Yong; Zhang

    2015-01-01

    Hepatitis B virus(HBV) is a hepatotropic DNA virus and its infection results in acute or chronic hepatitis. It is reported that the host innate immune system contributes to viral control and liver pathology, while whether and how HBV can trigger the components of innate immunity remains controversial. In recent years, the data accumulated from HBV-infected patients, cellular and animal models have challenged the concept of a stealth virus for HBV infection. This editorial focuses on the current findings about the innate immune recognition to HBV. Such evaluation could help us to understand HBV immunopathogenesis and develop novel immune therapeutic strategies to combat HBV infection.

  17. Immunizations in Children Requiring Warfarin Therapy.

    Science.gov (United States)

    Bauman, Mary E; Hawkes, Michael; Bruce, Aisha; Siddons, Suzanne; Massicotte, Patti

    2016-11-01

    Children with conditions requiring chronic warfarin therapy have increased. The importance of receiving immunizations in this population is magnified due to potential weakness in their immune response. There is concern about immunizing on therapeutic anticoagulation due to risk of hematomas and the influence of vaccine on warfarin metabolism. This study evaluated the influence of vaccines on warfarin effect as measured by the International Normalized Ratio and the clinically relevant hematomas or bruising postimmunization. There were no clinically relevant negative outcomes postimmunizations. This study demonstrates that immunizations may be safely administered to children receiving therapeutic warfarin therapy.

  18. Candida Immunity

    Directory of Open Access Journals (Sweden)

    Julian R. Naglik

    2014-01-01

    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  19. Immune modulation in chronic hepatitis B patients

    NARCIS (Netherlands)

    A.B. van Nunen

    2002-01-01

    textabstractThe hepatitis B virus (HBV) is a 42 nm viral particle and member of the hepadnaviridae family. Its double-shelled structure consists of an outer envelop composed of surface proteins (HBsAg) and an inner capsid formed by core-proteins (HBcAg) surrounding the partially double stranded DNA

  20. Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice.

    Science.gov (United States)

    Gros, Angèle; Syvannarath, Varouna; Lamrani, Lamia; Ollivier, Véronique; Loyau, Stéphane; Goerge, Tobias; Nieswandt, Bernhard; Jandrot-Perrus, Martine; Ho-Tin-Noé, Benoît

    2015-08-20

    Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI(-/-) mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI(-/-) mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI, and blocking of GPVI signaling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil-damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches.

  1. Pauci-immune lupus nephritis: possibility or co-incidence?

    Science.gov (United States)

    Cansu, Döndü Üsküdar; Temiz, Gökhan; Açıkalın, Mustafa F.; Korkmaz, Cengiz

    2017-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with immune complex formation and renal involvement of lupus and may include several kinds of pathological conditions, but mostly, it is associated with immune complex-induced glomerular disease. Pauci-immune lupus nephritis is a very rare condition. We describe a 45-year-old female patient with pauci-immune crescentic necrotizing lupus nephritis and briefly discuss the possible mechanism and pathogenesis.

  2. Resources, stress, and immunity: an ecological perspective on human psychoneuroimmunology.

    Science.gov (United States)

    Segerstrom, Suzanne C

    2010-08-01

    Ecological immunology provides a broad theoretical perspective on phenotypic plasticity in immunity, that is, changes related to the value of immunity across different situations, including stressful situations. Costs of a maximally efficient immune response may at times outweigh benefits, and some aspects of immunity may be adaptively suppressed. This review provides a basic overview of the tenets of ecological immunology and the energetic costs of immunity and relates them to the literature on stress and immunity. Sickness behavior preserves energy for use by the immune system, acute stress mobilizes "first-line" immune defenders while suppressing more costly responses, and chronic stress may suppress costly responses in order to conserve energy to counteract the resource loss associated with stress. Unexpected relationships between stress "buffers" and immune functions demonstrate phenotypic plasticity related to resource pursuit or preservation. In conclusion, ecological models may aid in understanding the relationship between stress and immunity.

  3. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  4. Immune responses to improving welfare.

    Science.gov (United States)

    Berghman, L R

    2016-09-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that "increased vigilance of the immune system is by definition better" because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as "sickness behavior," includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  5. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature

    Science.gov (United States)

    Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

    2016-01-01

    Patient: Female, 34 Final Diagnosis: Refractory thrombotic thrombocytopenic purpura Symptoms: Fatigue Medication: — Clinical Procedure: Plasma exchange Specialty: Rheumatology • Hematology and Critical Care Objective: Rare co-existance of disease or pathology Background: Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. Case Report: We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet

  6. EB病毒感染对住院新生儿血小板减少的影响%Epstein-Barr Virus Infection of Newborn Thrombocytopenic

    Institute of Scientific and Technical Information of China (English)

    杨燕; 金晓希; 曾真

    2014-01-01

    Objective Inquired into EB virus infection of newborn thrombocytopenic.Methods A an-alysed 96 cases of newborn thrombocytopenic in 2 years,determine the IgM antibodies of EB virus capsid and IgG antibodies , than diagnostic the EBV DNA of EB virus.Their mothers was simultaneously tested as well.Results 96 cases of newborn with thrombocytopenia in 34 cases with EB virus infection.Among them, 30 cases (31.25%) were detected EBV DNA positive;10 cases (10.42%) were EBV-CA-IgM positive;19 cases (19.79%) of EBV-EA-D-IgG positive;mothers were confirmed to be infected in 23 cases, 20 of them were EBV DNA positive and seven of them were EBV-CA-IgM positive, ten cases were EBV-EA-D-IgG posi-tive.Conclusion EB virus infection of newborn thrombocytopenic show the symptoms such as critical condi -tion , various of complications and slow recovery.Better curative effect can be accomplished if it gets the diag-nosis and treatment on time.%目的:探讨EB病毒感染对住院新生儿血小板减少的影响。方法分析2年来本院收治的96例新生儿血小板减少患儿,均检测EB病毒衣壳Ig M抗体、早期抗原IgG抗体及检测EBV DNA测定EB病毒;并对其母亲进行同期检测。结果96例血小板减少患儿中检出EB病毒感染34例,其中30例(31.25%)检测出EBV DNA阳性,EBV-CA-IgM阳性10例(10.42%),EBV-EA-D-IgG阳性19例(19.79%);患儿母亲确证感染23例,其中EBV DNA阳性20例, EBV-CA-IgM阳性7例,EBV-EA-D-IgG阳性10例。结论 EB病毒感染引起住院新生儿血小板减少症患者程度重,合并症多且恢复慢,如早诊断并及时治疗可取得较好疗效。

  7. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Prevention > Immunizations > Immunizations: Active vs. Passive Safety & Prevention Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can ...

  8. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

    Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

  9. Púrpura trombocitopênica idiopática na infância: estudo de base populacional no Catar Idiopathic thrombocytopenic purpura in childhood: a population-based study in Qatar

    Directory of Open Access Journals (Sweden)

    Naima Al-Mulla

    2009-06-01

    Full Text Available OBJETIVO: Definir o padrão da púrpura trombocitopênica idiopática (PTI (aguda/crônica, e descrever seus sintomas e características clínicas em crianças com menos de 14 anos de idade em uma sociedade árabe recentemente desenvolvida. MÉTODOS: Este estudo descritivo retrospectivo foi realizado no Departamento de Pediatria do Hospital Geral de Hamad, Hamad Medical Corporation, Catar. Foram incluídas neste estudo 50 crianças com idade inferior a 14 anos e diagnóstico de PTI durante o período de 2000 a 2005. RESULTADOS: Das crianças estudadas (50, 62% foram diagnosticadas com PTI aguda e 38% com PTI crônica. A PTI aguda foi mais prevalente em meninos (64,5% em comparação com meninas (35,5%, enquanto que a PTI crônica apresentou uma distribuição quase igual em meninos (57,9% e meninas (42,1%. História de infecção viral foi comum em casos de PTI tanto aguda (71% quanto crônica (63,2%; 68% das crianças com PTI apresentaram contagem de plaquetas abaixo de 20x10(9/L ao diagnóstico. A maioria das crianças estudadas (74% foi tratada com imunoglobulina intravenosa. CONCLUSÕES: O estudo revelou uma alta incidência de PTI entre as crianças no Catar. As descobertas do estudo são semelhantes às de outros relatos internacionais.OBJECTIVE: To find the pattern of idiopathic thrombocytopenic purpura (ITP (acute/chronic and to describe presenting features and clinical characteristics of the disease in children below 14 years of age in a newly developed Arabian society. METHODS: This retrospective, descriptive study was carried out at the Pediatric Department of the Hamad General Hospital, Hamad Medical Corporation, Qatar. A total of 50 children below 14 years of age who were diagnosed with ITP during the period 2000-2005 were included. RESULTS: Among the studied children (50, 62% were diagnosed with acute ITP and 38% with chronic ITP. Acute ITP was more prevalent in boys (64.5% when compared with girls (35.5%, whereas for chronic ITP

  10. Immunizations Part II: Shingles Vaccine

    Centers for Disease Control (CDC) Podcasts

    2008-09-24

    This podcast discusses older adults and shingles, as well as the importance of getting the shingles vaccine. It is primarily targeted to public health and aging services professionals.  Created: 9/24/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) and National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/24/2008.

  11. The accuracy of platelet counting in thrombocytopenic blood samples distributed by the UK National External Quality Assessment Scheme for General Haematology.

    Science.gov (United States)

    De la Salle, Barbara J; McTaggart, Paul N; Briggs, Carol; Harrison, Paul; Doré, Caroline J; Longair, Ian; Machin, Samuel J; Hyde, Keith

    2012-01-01

    A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making.

  12. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk.

  13. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  14. Extrahepatic manifestations of chronic viral hepatitis.

    Science.gov (United States)

    Pyrsopoulos, N T; Reddy, K R

    2001-02-01

    Hepatitis B (HBV) and C (HCV) viruses are well-recognized causes for chronic hepatitis, cirrhosis, and even for hepatocellular carcinoma. Apart from liver disease, these viral infections are known to be associated with a spectrum of extrahepatic manifestations. The prevalence of clinically significant extrahepatic manifestations is relatively low, but it can be associated with significant morbidity and even mortality. An awareness and recognition of these manifestations is of paramount importance in facilitating early diagnosis and in offering treatment. However, treatments are not necessarily effective, and patients may continue with disabling extrahepatic manifestations. Hepatitis B virus has been well recognized as causing a variety of manifestations that include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis. More recently, infection with hepatitis C virus has elicited considerable interest for its role in a spectrum of extrahepatic manifestations. Among the best-reported are cryoglobulinemia, glomerulonephritis, high titer of autoantibodies, idiopathic thrombocytopenic purpura, lichen planus, Mooren's corneal ulcer, Sjögren's syndrome, porphyria cutanea tarda, and necrotizing cutaneous vasculitis. The precise pathogenesis of these extrahepatic complications has not been determined, although the majority represent the clinical expression of autoimmune phenomena.

  15. Crosstalk between platelets and the complement system in immune protection and disease.

    Science.gov (United States)

    Verschoor, A; Langer, H F

    2013-11-01

    Platelets have a central function in repairing vascular damage and stopping acute blood loss. They are equally central to thrombus formation in cardiovascular diseases such as myocardial infarction and ischaemic stroke. Beyond these classical prothrombotic diseases, immune mediated pathologies such as haemolytic uraemic syndrome (HUS) or paroxysmal nocturnal haemoglobinuria (PNH) also feature an increased tendency to form thrombi in various tissues. It has become increasingly clear that the complement system, part of the innate immune system, has an important role in the pathophysiology of these diseases. Not only does complement influence prothrombotic disease, it is equally involved in idiopathic thrombocytopenic purpura (ITP), an autoimmune disease characterised by thrombocytopenia. Thus, there are complex interrelationships between the haemostatic and immune systems, and platelets and complement in particular. Not only does complement influence platelet diseases such as ITP, HUS and PNH, it also mediates interaction between microbes and platelets during systemic infection, influencing the course of infection and development of protective immunity. This review aims to provide an integrative overview of the mechanisms underlying the interactions between complement and platelets in health and disease.

  16. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

    Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung

  17. Investigation of erythrocyte immune dysfunction and related factors in patients with chronic kidney disease%慢性肾脏病患者红细胞免疫功能异常及相关因素探讨

    Institute of Scientific and Technical Information of China (English)

    夏春英; 姚利群; 邵维斌; 李倩; 荀康; 朱莉; 彭淑娟

    2013-01-01

    Objective: To explore the correlation of erythrocyte immune function and glomerular filtration rate (eGFR),parathyroid hormone (PTH) in the patients with chronic kidney disease ( CKD) . Methods: According to eGFR,60 patients with CKD were divided into three groups; CKD1-2 group, CKD3-4 group, CKD5 with non-the dialysis group. There were 20 cases in each group. There were also 20 cases in healthy control group. Intact parathyroid hormone (iPTH) was determined by radioimmunoassay, erythrocyte immune function was showed by the receptor rosette rate (RCR) of C3b of red cell membrane which analyzed by the Guo Feng's Method. Results: As eGFR decreased, iPTH level increased gradually and the RCR decreased progressively. The difference between CKD3-4 group and CKD5 group, and the difference between healthy control group and CKD1-2 group was significant (P <0. 05). As the renal function declined and the Hb level decreased, the difference between CKD3-4 group and CKD5 group,and the difference between healthy control group and CKD1-2 group was significant(P < 0. 05). With the deterioration of calcium and phosphorus metabolism disorders, CKD5 group had lower blood calcium level and higher blood phosphorus level compared with CKD1-2 group and CKD3-4 group. Pearson correlation analysis;the RCR level of the patients in CKD3-4 group and CKD5 group was negatively correlated with iPTH level ( r =-0. 36, P < 0. 05 ) , positively correlated with hemoglobin level and eGFR ( r = 0. 46, 0. 41, respectively,P <0. 05). Conclusion: Decreased renal function and significantly high PTH level in CKD patients may weaken erythrocyte immune function.%目的:探讨慢性肾脏病(CKD)患者红细胞免疫功能与肾小球滤过率(eGFR)及甲状旁腺激素(PTH)的相关性.方法:CKD患者60例,按eGFR分为CKD1-2期、CKD3-4期、非透析CKD5期组,每组各20例,同期正常体检者20例为健康对照组.全段甲状旁腺激素(iPTH)采用放射免疫法检测;红细胞

  18. Free-living amoebae: pathogenicity and immunity.

    Science.gov (United States)

    Ferrante, A

    1991-01-01

    Free-living amoebae causes three well-defined disease entities: (i) primary amoebic meningoencephalitis, caused by Naegleria fowleri, (ii) granulomatous amoebic encephalitis and (iii) chronic amoebic keratitis, caused by species of Acanthamoeba. Both Naegleria infections and chronic amoebic keratitis occur in healthy individuals while granulomatous amoebic encephalitis is often associated with patients with acquired immunodeficiencies. The different pathogenic behaviour of these organisms is associated with differences in life cycle, amoeboidal locomotion, enzyme composition (such as phospholipase A), and cytotoxins, as well as natural host immunity. Immunity against these amoebae (whether acquired or natural) involves a combination of complement, antibody and cell-mediated immunity. Evidence suggests that the major mechanisms of immunity against these amoebae is activation of phagocytic cells, especially neutrophils, by lymphokines and opsonization of the amoebae by antibody which promote an antibody dependent cellular destruction of the organism.

  19. 肠内免疫营养在慢性阻塞性肺疾病治疗中的应用%Clinical application of enteral immune nutrition for chronic obstructive pulmonary disease patients

    Institute of Scientific and Technical Information of China (English)

    张国玉; 邹剑峰

    2015-01-01

    目的 探讨应用肠内免疫营养制剂对于慢性阻塞性肺疾病(COPD)患者营养状况改善效果及对免疫和急性炎性反应的影响.方法 2013年6月至2014年6月在海军总医院重症医学科住院需行机械通气的60例COPD患者,随机分为两组:免疫营养组30例和标准营养组30例.两组使用等热量肠内营养.营养素经鼻肠管使用.入院当天及每2周抽取静脉血,检测血清白蛋白(ALB)、前白蛋白(PA),C反应蛋白(CRP),白细胞介素-6(IL-6),同时在床旁测上臂肌围(MAMC)各指标,比较2组14d脱机率及机械通气时间.结果 免疫营养组患者治疗14d内的脱机率和高于匀浆膳营养组(73.3%比43.3%,P<0.05);营养指标:第14天的前白蛋白水平[(188.4±57.5) mg/L比(174.6 ±65.7) mg/L,P<0.05]、第14天的白蛋白水平[(32.7±4.6) g/L比(30.2 ±3.8)g/L,P<0.05]、第28天时的上臂肌围水平高于对照组[(25.5±2.l)cm比(24.3±1.8)cm,P<0.05],差异均有统计学意义.炎症反应参数,IL-6水平第14天时[(250.1±110.3) ng/L比(266.1±97.3)ng/L,P>0.05],两组差异无统计学意义,第28天时[(108.5±59.6)ng/L比(165.7±76.3)ng/L,P<0.05]免疫营养组水平低于标准营养组;CRP水平:第14天时CRP水平[(12.2±7.3)mg/L比(13.2±6.9) mg/L,P<0.05],第28天的CRP水平[(7.5±5.0)mg/L比(9.6±5.6) mg/L,P<0.05],免疫营养组CRP水平在第14、28天均低于标准营养组,差异有统计学意义.结论 COPD患者应用免疫肠内营养支持较匀浆膳能更好地改善患者营养状态、免疫功能、下调急性炎症反应水平.提高早期撤机成功率,是较为合适的营养支持方法.%Objective To explore the application of enteral immune nutrition preparation for chronic obstructive pulmonary disease (COPD) patients and examine the improving effects on nutritional status,immune status and acute inflammatory reaction.Methods A total of 60 cases of hospitalized COPD patients on mechanical ventilation in intensive care

  20. Study on effect of immune enteral nutrition in patients with chronic obstructive pulmonary disease with typeⅡrespiratory failure in patients with immune recovery%免疫肠内营养对慢性阻塞性肺疾病合并Ⅱ型呼吸衰竭患者免疫恢复情况的疗效研究

    Institute of Scientific and Technical Information of China (English)

    杨奉民

    2014-01-01

    Objective To study the clinical effect of immune enteral nutrition for patients with chronic obstructive pulmonary disease (COPD) combined with typeⅡrespiratory failure recovery. Method Selected 104 patients with COPD combined with typeⅡrespiratory failure in our hospital from February 2010 to June 2013. Devided into control group and observation group, each group of 52 cases via the method of random grouping. Two groups were treated with anti infection and clinical treatment. Observation group used immuned enteral nutrition while control group used routine enteral nutrition support. Compared the effect of two groups. Result The pulmonary function level (FEV1 and FVC) of two groups before treatment had no significant difference (Pal >0.05). The FEV1 and FVC of observation group after treatment respectively were (1.98±0.41) L and (2.83±0.66) L, which were signiifcantly higher than that of control group [(1.69±0.44) L, (2.42±0.74) L], the differences were statistical signiifcance (P<0.05). After nutritional support, both pH and PaO2 levels of two groups were increased, but observation group increased more, the differences were statistically signiifcant (Pal <0.05). The PaCO2 leves of both groups decreased and observation group decreased more, the difference was statistically signiifcant (P < 0.05). Conclusion Immune enteral nutrition can support reasonable needs for patients with COPD complicated with respiratory failure disease type Ⅱ , it helps patients adjust the lung function and blood gas levels, increased patient immunity, better, economic security, worthy of clinical used and recommended.%目的:研究免疫肠内营养对慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭患者免疫恢复情况的疗效。方法选取本院2010年2月至2013年6月收治的104例COPD合并Ⅱ型呼吸衰竭患者作为研究对象。以数字法随机分为观察组和对照组,每组各52例。两组患者均给予相关抗感染及临床治疗。观

  1. Immune-mediated hemolytic anemia.

    Science.gov (United States)

    Rosse, Wendell F; Hillmen, Peter; Schreiber, Alan D

    2004-01-01

    Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fc gamma receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is

  2. IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

    2016-03-01

    Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

  3. Idiopathic thrombocytopenic purpura (ITP)

    Science.gov (United States)

    Blood tests will be done to check your platelet count . A bone marrow aspiration or biopsy may also be done. ... the disease usually goes away without treatment. Some children ... the platelet count in about half of people. However, other drug ...

  4. Microbial Biofilms and Chronic Wounds

    Science.gov (United States)

    Omar, Amin; Wright, J. Barry; Schultz, Gregory; Burrell, Robert; Nadworny, Patricia

    2017-01-01

    Background is provided on biofilms, including their formation, tolerance mechanisms, structure, and morphology within the context of chronic wounds. The features of biofilms in chronic wounds are discussed in detail, as is the impact of biofilm on wound chronicity. Difficulties associated with the use of standard susceptibility tests (minimum inhibitory concentrations or MICs) to determine appropriate treatment regimens for, or develop new treatments for use in, chronic wounds are discussed, with alternate test methods specific to biofilms being recommended. Animal models appropriate for evaluating biofilm treatments are also described. Current and potential future therapies for treatment of biofilm-containing chronic wounds, including probiotic therapy, virulence attenuation, biofilm phenotype expression attenuation, immune response suppression, and aggressive debridement combined with antimicrobial dressings, are described. PMID:28272369

  5. [Chronic inflammatory bowel diseases in cats].

    Science.gov (United States)

    Ghermai, A K

    1989-01-01

    The aetiology of chronic idiopathic intestinal inflammation is unknown. It is characterized by a diffuse infiltration with inflammatory cells into the intestinal mucosa and sometimes submucosa. Cats with chronic intermittent vomiting and diarrhoea, later on accompanied by anorexia and weight loss, are presented. Definitive diagnosis can be obtained by intestinal biopsy only. An immune pathogenesis is suspected, which is supported by the fact, that chronic inflammatory bowel disease responds to steroid therapy.

  6. Obesity leptin and the immune system

    Directory of Open Access Journals (Sweden)

    Padiotis. K.

    2011-04-01

    Full Text Available The increasing prevalence of obesity in developed and developing countries raises a major health concern due to the fact that obesity and nutrition are associated with impaired immune responses. Overconsumption of nutrients alters several functions of the immune defence mechanisms leading to severe infection and chronic diseases. The hormone leptin, known to regulate energy balance has been proved to activate several components of signalling pathways having thus immunoregulatory activity. The aim of this paper is to present the connections between obesity, immune system mechanisms and the role of the adipocyte hormone leptin

  7. Chronic cholecystitis

    Science.gov (United States)

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  8. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  9. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  10. Adipose Tissue Immunity and Cancer

    Directory of Open Access Journals (Sweden)

    Victoria eCatalan

    2013-10-01

    Full Text Available Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete proinflammatory adipokines and cytokines providing a microenvironment favourable for tumour growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching towards M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumour growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumour cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumour microenvironment with more sophisticated and selective anti-tumoural drugs.

  11. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  12. Resolution of chronic hepatitis C following parasitosis

    Institute of Scientific and Technical Information of China (English)

    Valerie Byrnes; Sanjiv Chopra; Margaret J Koziel

    2007-01-01

    An inefficient cellular immune response likely leads to chronic hepatitis C virus (HCV) infection. Resolution of chronic HCV infection in the absence of treatment is a rare occurrence. We report the case of a 39-year old white male with a 17-year history of chronic HCV infection, who eradicated HCV following a serious illness due to co-infection with Babesia (babesiosis), Borriela Borgdorferi (Lyme disease) and Ehrlichia (human granulocytic ehrlichiosis). We hypothesize that the cellular immune response mounted by this patient in response to his infection with all three agents but in particular Babesia was sufficient to eradicate HCV.

  13. Unintended events following immunization with MMR: a systematic review.

    Science.gov (United States)

    Jefferson, Tom; Price, Deirdre; Demicheli, Vittorio; Bianco, Elvira

    2003-09-08

    Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases.

  14. 慢性氨暴露对中华鳖幼鳖生长及非特异性免疫反应的影响%Effects of chronic ammonia exposure on growth and non specific immune responses of juvenile soft-shelled turtle Pelodiscus immune responses of juvenile soft-shelled turtle Pelodiscus sinensis

    Institute of Scientific and Technical Information of China (English)

    陈欣然; 牛翠娟; 蒲丽君

    2006-01-01

    Soft-shelled turtles are often exposed to high ambient ammonia levels in intensive rearing conditions. This work evaluated the effects of chronic ammonia exposure on growth and nonspecific immune parameters in juvenile soft-shelled in juvenile soft-shelled turtles Pelodiscus sinensi. Turtles (body weight: 90.5±20.5 g) were subjected to three ammonia concentrations, 1.5 concentrations, 1.5mg/L (C1), 2.6 mg/L (C2) and 4.1 mg/L (C3) unionized ammonia nitrogen (UIA-N) for 84 days. A control group ntrol group (C0) was also set up, in which the animals were reared in tap water with no extrinsic NH4Cl. Consistent ambient temrinsic NH4Cl. Consistent ambient temperatures (29.5 ± 0.5℃ ) and pH (7.8 ± 0.1 ) in each treatment were maintained throughout the experiment. Body n each treatment were maintained throughout the experiment. Body weight was measured at 21, 42 and 84 days after initiation of ammonia exposure. Blood was sampled on day 84 after inixposure. Blood was sampled on day 84 after initiation of ammonia exposure. In the present concentration range, ammonia showed no clear influence on the turtle's ammonia showed no clear influence on the turtle's growth. Also, ammonia had no significant effects on non-specific immune parameters such as serum hemolytic activity, immune parameters such as serum hemolytic activity,bactericidal activity, bacteriolytic activity and the spleen index. However, the non-specific a-naphathyl acetate esterase However, the non-specific a-naphathyl acetate esterase (ANAE) positive ratios of the blood and spleen lymphocytes both declined in the ammonia treatment groups in relation to th declined in the ammonia treatment groups in relation to the control. The present results indicate that the turtle is fairly resistant to ammonia and may be able to endure much ant to ammonia and may be able to endure much higher ambient ammonia levels than fish.%在高密度养殖模式下,中华鳖经常暴露于高氨环境中.本研究评价了

  15. Inflammation and immune system interactions in atherosclerosis.

    Science.gov (United States)

    Legein, Bart; Temmerman, Lieve; Biessen, Erik A L; Lutgens, Esther

    2013-10-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 16.7 million deaths each year. The underlying cause of the majority of CVD is atherosclerosis. In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall. Today's picture is far more complex. Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid-sized arteries. Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis. By transforming immune cells into pro- and anti-inflammatory chemokine- and cytokine-producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke. In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis.

  16. The immune system vs. Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Givskov, Michael; Bjarnsholt, Thomas

    2010-01-01

    revealed both innate as well as adaptive immune responses to biofilms. On the other hand, measures launched by biofilm bacteria to achieve protection against the various immune responses have also been demonstrated. Whether particular immune responses to biofilm infections exist remains to be firmly...... established. However, because biofilm infections are often persistent (or chronic), an odd situation appears with the simultaneous activation of both arms of the host immune response, neither of which can eliminate the biofilm pathogen, but instead, in synergy, causes collateral tissue damage. Although...... the present review on the immune system vs. biofilm bacteria is focused on Pseudomonas aeruginosa (mainly because this is the most thoroughly studied), many of the same mechanisms are also seen with biofilm infections generated by other microorganisms....

  17. Chronic prostatitis

    OpenAIRE

    Le, Brian; Schaeffer, Anthony J.

    2011-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  18. Chronic prostatitis

    OpenAIRE

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  19. Immunity and immune modulation in Trypanosoma cruzi infection.

    Science.gov (United States)

    Cardillo, Fabíola; de Pinho, Rosa Teixeira; Antas, Paulo Renato Zuquim; Mengel, José

    2015-12-01

    Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.

  20. [Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition].

    Science.gov (United States)

    Pita-Ramírez, L; Hurtado-Monroy, R; Labardini-Méndez, J

    1992-01-01

    A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura.

  1. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  2. [Splenectomy in chronic idiopathic thrombopenic purpura in adults. Apropos of 49 cases].

    Science.gov (United States)

    Melki, J; Dauce, J P; Kunlin, A; Tilly, H; Julien, J P; Monconduit, M; Piguet, H

    1989-01-01

    The authors reviewed the case files of 49 adult patients undergoing splenectomy for chronic idiopathic thrombocytopenic purpura at the Centre Henri Becquerel between 1970 and 1987. Although the postoperative course was straightforward in 83.7% of cases, one reoperation for subphrenic abscess was necessary and there was one postoperative death. Remission from thrombocytopenia was obtained in 87.5% of the patients, but only transiently in 8.5% of them. No preoperative predictive factors could be demonstrated. An early postoperative rise in the platelet count to more than 500 G/litre appears to ensure a good subsequent result. Secondary infectious complications are not exceptional and can be fatal (one death in our series); they require prophylaxis by anti-pneumococcal vaccination. The place of prophylactic antibiotic therapy has yet to be defined.

  3. Immune-mediated diseases in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.

    2011-01-01

    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant im

  4. Immune-mediated canine and feline keratitis.

    Science.gov (United States)

    Andrew, Stacy E

    2008-03-01

    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

  5. Innate immune signaling in cardiac ischemia

    NARCIS (Netherlands)

    Arslan, F.; de Kleijn, D.P.V.; Pasterkamp, G.

    2011-01-01

    Despite advances in treatment of patients who suffer from ischemic heart disease, morbidity related to myocardial infarction is increasing in Western societies. Acute and chronic immune responses elicited by myocardial ischemia have an important role in the functional deterioration of the heart. Res

  6. Future targets for immune therapy in colitis?

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Claesson, M H

    2008-01-01

    Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against...

  7. The immune system in the aging human.

    Science.gov (United States)

    Rymkiewicz, Paulina Dominika; Heng, Yi Xiong; Vasudev, Anusha; Larbi, Anis

    2012-09-01

    With the improvement of medical care and hygienic conditions, there has been a tremendous increment in human lifespan. However, many of the elderly (>65 years) display chronic illnesses, and a majority requires frequent and longer hospitalization. The robustness of the immune system to eliminate or control infections is often eroded with advancing age. Nevertheless, some elderly individuals do cope better than others. The origin of these inter-individual differences may come from genetic, lifestyle conditions (nutrition, socio-economic parameters), as well as the type, number and recurrence of pathogens encountered during life. The theory we are supporting is that chronic infections, through life, will induce profound changes in the immune system probably due to unbalanced inflammatory profiles. Persistent viruses such a cytomegalovirus are not eliminated and are a driven force to immune exhaustion. Because of their age, elderly individuals may have seen more of these chronic stimulators and have experienced more reactivation episodes ultimately leading to shrinkage of their repertoire and overall immune robustness. This review integrates updates on immunity with advancing age and its impact on associated clinical conditions.

  8. Immunity and immunization in elderly.

    Science.gov (United States)

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  9. A preliminary study to evaluate the immune responses induced by immunization of dogs with inactivated Ehrlichia canis organisms

    Directory of Open Access Journals (Sweden)

    Sunita Mahan

    2005-09-01

    Full Text Available Ehrlichia canis is an intracellular pathogen that causes canine monocytic ehrlichiosis. Although the role of antibody responses cannot be discounted, control of this intracellular pathogen is expected to be by cell mediated immune responses. The immune responses in dogs immunized with inactivated E. canis organisms in combination with Quil A were evaluated. Immunization provoked strong humoral and cellular immune responses, which were demonstrable by Western blotting and lymphocyte proliferation assays. By Western blotting antibodies to several immunodominant E. canis proteins were detected in serum from immunized dogs and antibody titres increased after each immunization. The complement of immunogenic proteins recognized by the antisera were similar to those recognized in serum from infected dogs. Upon challenge with live E. canis, rapid anamnestic humoral responses were detected in the serum of immunized dogs and primary antibody responses were detected in the serum from control dogs. Following immunization, a lymphocyte proliferative response (cellular immunity was detected in peripheral blood mononuclear cells (PBMNs of immunized dogs upon stimulation with E. canis antigens. These responses were absent from non-immunized control dogs until after infection with live E. canis, when antigen specific-lymphocyte proliferation responses were also detected in the PBMNs of the control dogs. It can be thus concluded that immunization against canine monocytic ehrlichiosis may be feasible. However, the immunization regimen needs to be optimized and a detailed investigation needs to be done to determine if this regimen can prevent development of acute and chronic disease.

  10. [Chronic inflammatory demyelinating polyradiculoneuropathy].

    Science.gov (United States)

    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  11. [Systemic immunological response in children with chronic gingivitis and gastro-intestinal pathology].

    Science.gov (United States)

    Romanenko, E G

    2014-01-01

    Study of the immune system mechanisms in chronic catarrhal gingivitis in children with gastrointestinal pathology was performed in 102 children (49 with chronic gastritis and duodenitis and 53 with no signs of gastrointestinal pathology). Forty-eight children with healthy periodontium constituted control group. Generalized chronic catarrhal gingivitis in children with gastroduodenal pathology is characterized by intense humoral response by simultaneous T-cell immunity suppression. Detection of high serum titers of circulating immune complexes in patients with chronic catarrhal gingivitis suggests a role of immune response in the pathogenesis of periodontal disease increases with concomitant diseases of the upper gastrointestinal tract.

  12. Hyperglycemia, tumorigenesis, and chronic inflammation.

    Science.gov (United States)

    Chang, Shu-Chun; Yang, Wei-Chung Vivian

    2016-12-01

    Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative/effective therapeutic strategies for hyperglycemia-associated cancers.

  13. Evidence-based Treatment for a Newly Diagnosed Acute Idiopathic Thrombocytopenic Purpura in Children%一例初诊儿童急性特发性血小板减少性紫癜患者的循证治疗

    Institute of Scientific and Technical Information of China (English)

    吴星; 徐之良

    2010-01-01

    目的 结合1例初诊儿童急性特发性血小板减少性紫癜患者的循证治疗经过,总结评价治疗儿童急性特发性血小板减少性紫癜的最佳证据,为临床实践提供参考.方法 充分评估患者情况后,提出临床问题,从cochrane图书馆(2009年第4期)Medline(PbuMed网站1993年1月至2009年10月)中国知网知识总库上进行检索.检索检索主题词为:ildren acute immune thrombocytopenic purpura, platelet count, intracranial hemorrhage, Corticosteroids ,intravenous immuneglobulin,mega-dose methylprednisolon refractory itp, Rituximaba, splenectomy, human, children 0~8 years, systematic review, meta-analysis, randomized controlled trials.结果 检索出与不同问题相关的随机对照实验30篇,系统评价或Meta分析6篇,通过对检索结果进行分析,为患者制定了合理的治疗方案.经1年随访证实,该方案适合患者.结论 采用循证治疗的方法,为初治的儿童特发性血小板减少性紫癜患者确定合理的治疗目标和治疗方案,可有效提高治疗效果.

  14. Chronic pancreatitis in dogs.

    Science.gov (United States)

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  15. [Obesity and the immune system].

    Science.gov (United States)

    Muñoz, M; Mazure, R A; Culebras, J M

    2004-01-01

    With an increased prevalence of obesity in developed countries, associated chronic diseases rise in a parallel way. Morbidity secondary to overweight and obesity include type 2 diabetes, dislipemia, hypertension, heart disease, cerebrovascular disease, cholelithiasis, osteoarthritis, heart insufficiency, sleep apnoea, menstrual changes, sterility and psychological alterations. There is also a greater susceptibility to suffer some types of cancer, infections, greater risk of bacteremia and a prolonged time of wound healing after surgical operations. All these factors indicate that obesity exerts negative effects upon the immune system. Immune changes found in obesity and their possible interrelations are described in this article. Changes produced during obesity affect both humoral and cellular immunity. It is known that adipose tissue, together with its role as energy reserve in form of triglycerides, has important endocrine functions, producing several hormones and other signal molecules. Immune response can be deeply affected by obesity, playing leptin an important role. Properties of leptin, alterations of leptin levels in different situations and its changes with different medical and surgical therapies for obesity are described in this article.

  16. Regulation of hepatic innate immunity by hepatitis C virus

    OpenAIRE

    Stacy M Horner; Gale, Michael

    2013-01-01

    Hepatitis C virus (HCV) is a global public health problem involving chronic infection of the liver in over 170 million people. Chronic HCV causes liver disease and is linked with liver cancer. Viral innate immune evasion strategies and human genetic determinants underlie the transition of acute HCV infection to viral persistence and the support of chronic infection. Host genetic factors, such as sequence polymorphisms in IFNL3, a gene in the host interferon system, can influence both the outc...

  17. Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

    Science.gov (United States)

    ULAS, ARIFE; SILAY, KAMILE; AKINCI, SEMA; AKINCI, MUHAMMED BULENT; SENDUR, MEHMET ALI; DEDE, DIDEM SENER; POLAT, YUNUS HALIL; YALCIN, BULENT

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy. PMID:26622823

  18. Recurrent Thrombotic Thrombocytopenic Purpura-Like Syndrome as a Paraneoplastic Phenomenon in Malignant Peritoneal Mesothelioma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Francisco Socola

    2012-01-01

    Full Text Available We report the case of an African American male with no significant past medical history presenting with recurrent, rapidly relapsing episodes of thrombotic thrombocytopenic purpura (TTP despite aggressive treatment with several lines of treatment. Incidentally, these episodes were associated with severe abdominal pain which eventually developed into acute abdomen and prompted exploratory laparotomy, revealing diffuse carcinomatosis with a tumor located on the left pelvis that was encasing the distal sigmoid colon. Pathology made a final diagnosis of peritoneal mesothelioma. TTP-like syndrome (TTP-LS has been described as a paraneoplastic phenomenon in several malignancies but never before in the setting of malignant mesothelioma. Paraneoplastic TTP-like syndrome has historically been associated with a dismal prognosis and particular clinical and laboratory abnormalities described in this paper. It is of utmost importance to make a prompt determination whether TTP is idiopathic or secondary to an underlying condition because of significant differences in their prognosis, treatment, and response. This paper also reviews the current literature regarding this challenging condition.

  19. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    Science.gov (United States)

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m(-2) within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.

  20. The role of innate immunity in spontaneous regression of cancer

    Directory of Open Access Journals (Sweden)

    J A Thomas

    2011-01-01

    Full Text Available Nature has provided us with infections - acute and chronic - and these infections have both harmful and beneficial effects on the human system. Worldwide, a number of chronic infections are associated with a risk of cancer, but it is also known that cancer regresses when associated with acute infections such as bacterial, viral, fungal, protozoal, etc. Acute infections are known to cure chronic diseases since the time of Hippocrates. The benefits of these fever producing acute infections has been applied in cancer vaccinology such as the Coley′s toxins. Immune cells like the natural killer cells, macrophages and dendritic cells have taken greater precedence in cancer immunity than ever before. This review provides an insight into the benefits of fever and its role in prevention of cancer, the significance of common infections in cancer regression, the dual nature of our immune system and the role of the often overlooked primary innate immunity in tumor immunology and spontaneous regression of cancer.

  1. Guidelines on the use of intravenous immune globulin for hematologic conditions.

    Science.gov (United States)

    Anderson, David; Ali, Kaiser; Blanchette, Victor; Brouwers, Melissa; Couban, Stephen; Radmoor, Paula; Huebsch, Lothar; Hume, Heather; McLeod, Anne; Meyer, Ralph; Moltzan, Catherine; Nahirniak, Susan; Nantel, Stephen; Pineo, Graham; Rock, Gail

    2007-04-01

    Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions

  2. The immune system mediates blood-brain barrier damage; Possible implications for pathophysiology of neuropsychiatric illnesses

    NARCIS (Netherlands)

    VanderWerf, YD; DeJongste, MJL; terHorst, GJ

    1995-01-01

    The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses. In this investigation the effects of immune activation on the brain are characterized In order to study this, we used a model for chronic immune activation, the myocardial

  3. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Science.gov (United States)

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function. PMID:28246613

  4. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Directory of Open Access Journals (Sweden)

    Silvana Balzar

    2017-01-01

    Full Text Available Idiopathic chronic inflammatory conditions (ICIC such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system’s thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system’s compartmentalization in the pathogenesis of ICIC. The CDR concept’s relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

  5. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  6. Immune response to lipoproteins in atherosclerosis.

    Science.gov (United States)

    Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V

    2012-01-01

    Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  7. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  8. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  9. Understanding Herd Immunity.

    Science.gov (United States)

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  10. Epigenetic Dysfunction in Turner Syndrome Immune Cells.

    Science.gov (United States)

    Thrasher, Bradly J; Hong, Lee Kyung; Whitmire, Jason K; Su, Maureen A

    2016-05-01

    Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with T cell-specific UTX deficiency have impaired clearance of chronic viral infection due to decreased frequencies of T follicular helper (Tfh) cells, which are critical for B cell antibody generation. In parallel, TS patients have decreased Tfh frequencies in peripheral blood. Together, these findings suggest that haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune deficit, which may manifest as increased predisposition to chronic otitis media.

  11. Clinical study on recombinant human thrombopoietin in the treatment of refractory idiopathic thrombocytopenic purpura%重组人血小板生成素治疗难治性特发性血小板减少性紫癜临床观察

    Institute of Scientific and Technical Information of China (English)

    张晓丽; 刘延方; 孙慧; 谢新生; 姜中兴; 孙玲; 万鼎铭; 刘林湘

    2010-01-01

    Objective To observe the efficacy and toxicity of recombinant human thrombopoietin (rhTPO)in the treatment of chronic refractory idiopathic thrombocytopenic purpura(ITP).Methods Twenty- four patients with chronic ITP were administered with rhTPO subcutaneously at 300 IU/(kg · d)for 14 days or until the platelet count > 100 × 109/L.Results Out of 24 patients with ITP, 12 cases showed significant response and 5 cases showed good response to the treatment with rhTPO.The peak platelet count after treatment was(129 ± 97)× 109/L, significantly higher than the mean platelet count [(10 ±5)× 109/L]before treatment(t = 5.822, P <0.01).The agent was well tolerated in most patients.Conclusions rhTPO exerts satisfactory efficacy in the treatment of chronic ITP with mild side effects.%目的 观察重组人血小板生成素(rhTPO)治疗慢性难治性特发性血小板减少性紫癜(ITP)的临床疗效及不良反应.方法 24例慢性难治性ITP患者皮下注射rhTPO 300 IU/(kg·d),疗程14 d或血小板>100×109/L后停药.结果 24例患者rhTPO治疗后,显效12例,有效5例,用药前血小板平均值为(10±5)×109/L,治疗后血小板计数的升高的最高值为(129±97)×109/L,与用药前比较差异有统计学意义(t=5.822,P<0.01).多数患者对药物耐受良好.结论 rhTPO治疗慢性难治性ITP具有良好的疗效,不良反应轻微.

  12. Cell mediated immunity to fungi: a reassessment.

    Science.gov (United States)

    Romani, Luigina

    2008-09-01

    Protective immunity against fungal pathogens is achieved by the integration of two distinct arms of the immune system, the innate and adaptive responses. Innate and adaptive immune responses are intimately linked and controlled by sets of molecules and receptors that act to generate the most effective form of immunity for protection against fungal pathogens. The decision of how to respond will still be primarily determined by interactions between pathogens and cells of the innate immune system, but the actions of T cells will feed back into this dynamic equilibrium to regulate the balance between tolerogenic and inflammatory responses. In the last two decades, the immunopathogenesis of fungal infections and fungal diseases was explained primarily in terms of Th1/Th2 balance. Although Th1 responses driven by the IL-12/IFN-gamma axis are central to protection against fungi, other cytokines and T cell-dependent pathways have come of age. The newly described Th17 developmental pathway may play an inflammatory role previously attributed to uncontrolled Th1 responses and serves to accommodate the seemingly paradoxical association of chronic inflammatory responses with fungal persistence in the face of an ongoing inflammation. Regulatory T cells in their capacity to inhibit aspects of innate and adaptive antifungal immunity have become an integral component of immune resistance to fungi, and provide the host with immune defense mechanisms adequate for protection, without necessarily eliminating fungal pathogens which would impair immune memory--or causing an unacceptable level of tissue damage. The enzyme indoleamine 2,3-dioxygenase and tryptophan metabolites contribute to immune homeostasis by inducing Tregs and taming overzealous or heightened inflammatory responses.

  13. Autonomic nervous system and immune system interactions.

    Science.gov (United States)

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  14. Sleep, immunity and shift workers: A review

    Directory of Open Access Journals (Sweden)

    Carlos Mauricio Oliveira de Almeida

    2016-07-01

    Full Text Available To date, shift workers represent between 15% and 25% of the modern day workforce. Work time poses a great challenge to workers as it requires that they balance productivity and sleep time between shifts. As a result, these workers experience chronic sleep deprivation with increased fatigue and drowsiness due to this sleep deprivation. The impact of this kind of work on the immune system is not yet known. We conducted a literature review with the aim of evaluating articles on this specific type of work's effects on sleep and immunity.

  15. Adaptive Immunity to Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2009-09-01

    Full Text Available The precise role of adaptive immune responses in the clinical outcome of HCV infection is still only partially defined. Recent studies suggest that viral-host cell interactions during the acute phase of infection are essential for viral clearance or progression into chronic HCV infection. This review focuses on different aspects of the adaptive immune responses as determinants of the different outcomes of HCV infection, clearance or persistent infection, and outlines current concepts of HCV evasion strategies. Unravelling these important mechanisms of virus-host interaction will contribute to the development of novel strategies to prevent and control HCV infection.

  16. [Chronic and slow neuroinfections. Current status of problem].

    Science.gov (United States)

    Antonov, P V; Tsinzerling, V A

    2001-01-01

    Some causes and conditions of chronic and slow neuroinfections were reviewed: brain immunological "priveledge"; congenital immunodeficiencies including clinically latent; immunomodulation induced by microorganisms due to infection of immune cells, inactivation of cytokines making difficulties to antibodies; disorders of genetic control of immune reaction; immunopathologic processes are of great importance for the agents persistence including autoimmunity. Microorganisms can locate in the neurons, glyocytes, endothelium. Neuroinfections chronic course depends on the agents properties and peculiarities of nervous system reactivity.

  17. Ear infection - chronic

    Science.gov (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  18. Skin innate immune system

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    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  19. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins.

    Science.gov (United States)

    Rosenberg, A S; Pariser, A R; Diamond, B; Yao, L; Turka, L A; Lacana, E; Kishnani, P S

    2016-04-01

    Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology.

  20. Brucella spp. Virulence Factors and Immunity.

    Science.gov (United States)

    Byndloss, Mariana X; Tsolis, Renee M

    2016-01-01

    Brucellosis, caused by bacteria of the genus Brucella, is an important zoonotic infection that causes reproductive disease in domestic animals and chronic debilitating disease in humans. An intriguing aspect of Brucella infection is the ability of these bacteria to evade the host immune response, leading to pathogen persistence. Conversely, in the reproductive tract of infected animals, this stealthy pathogen is able to cause an acute severe inflammatory response. In this review, we discuss the different mechanisms used by Brucella to cause disease, with emphasis on its virulence factors and the dichotomy between chronic persistence and reproductive disease.

  1. Obesity, inflammation and the immune system.

    Science.gov (United States)

    de Heredia, Fátima Pérez; Gómez-Martínez, Sonia; Marcos, Ascensión

    2012-05-01

    Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

  2. 重组人血小板生成素治疗难治性特发性血小板减少性紫癜的循证评价%Evidence-based Evaluation of Recombinant Human Thromobopoietin for Refractory Idiopathic Thrombocytopenic Purpura

    Institute of Scientific and Technical Information of China (English)

    黄琳; 任晓蕾; 刘一; 李玉珍

    2011-01-01

    目的:评价重组人血小板生成素(rhTPO)治疗成人慢性难治性特发性血小板减少性紫癜(ITP)的有效性与安全性.方法:采用循证医学的文献分析评价方法,计算机检索CBM、CNKI、MEDLINE、EMbase、Cochrane图书馆临床对照试验资料库等数据库,收集rhTPO治疗成人慢性难治性ITP的临床研究证据.结果:检索到rhTPO治疗成人慢性难治性ITP的文献有:自身前后对照试验5篇,随机对照试验2篇.按Jadad量表评分:1篇随机对照研究质量较高,为4分,其余文献均小于3分.5项自身对照研究结果基本一致,认为rhTPO可升高成人难治性ITP患者的血小板计数,且不良反应轻微.2项随机对照试验认为rhTPO联合达那唑治疗难治性ITP的效果明显优于单用达那唑,且对于单用达那唑治疗无效者,接受rhTPO治疗后血小板计数亦明显升高.结论:现有研究显示rhTPO在治疗成人慢性难治性ITP方面疗效确切、安全性好,但试验设计存在不足,尚需进行设计良好的大样本研究.%OBJECTIVE: To evaluate the efficacy and safety of recombinant human thromobopoietin (rhTPO) for adult chronic refractory idiopathic thrombocytopenic purpura (ITP).METHODS: By literature analysis based on evidence-based medicine, clinical trials about rhTPO in the treatment of adult chronic refractory ITP were retrieved from CMB, CNKI, MEDLINE, EMbase and Cochrane library.RESULTS: Of collected pertinent literature about rhTPO in the treatment of adult chronic refractory ITP, five were self-control studies and two were randomized controlled trials (RCTs).The quality of seven studies was evaluated according to Jadad scale, of which one scored four points, and the others below three points.The five self-control studies all supported that rhTPO could effectively elevate the platelet counts and was safe for patients with adult chronic refractory ITP.Two RCTs indicated that rhTPO combined with danazol was more effective than danazol for

  3. Púrpura trombocitopênica trombótica associada à gravidez: relato de caso Thrombotic thrombocytopenic purpura associated with pregnancy: case report

    Directory of Open Access Journals (Sweden)

    Edson Silva Marques Filho

    2009-08-01

    Full Text Available A púrpura trombocitopênica trombótica (PTT é uma entidade rara em pacientes críticos. Relatamos um caso clínico de paciente gestante admitida em unidade de terapia intensiva obstétrica com quadro de alteração de sensório, atribuído inicialmente à doença hipertensiva da gravidez. Evoluiu com piora do quadro geral caracterizada por anemia e plaquetopenia grave, suscitando a investigação diagnóstica de púrpura trombocitopênica trombótica após o reconhecimento do perfil hematológico. Os autores enfatizam a importância do conhecimento da doença como marcador de prognóstico para pacientes obstétricas, em vista da semelhança com outras patologias comuns ao ciclo gravídico-puerperal e o fato do diagnóstico e tratamento precoce serem determinantes para o desfecho.Case report of a patient with 37-week gestational age admitted to an obstetric intensive care unit with an altered level of consciousness, related primarily to the pregnancy-induced hypertension. The patient presented a worsening clinical course characterized by, anemia and severe thrombocytopenia, Investigation led to a diagnostic of thrombotic thrombocytopenic purpura after the hematological profile was assessed. The authors emphasize the importance of the disease recognition as a prognostic marker for obstetric patients, in view of the similarity with other common morbidities during pregnancy and the importance of timely diagnosis and early treatment as determinant factors for the outcome.

  4. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

    Science.gov (United States)

    Grall, Maximilien; Azoulay, Elie; Galicier, Lionel; Provôt, François; Wynckel, Alain; Poullin, Pascale; Grange, Steven; Halimi, Jean-Michel; Lautrette, Alexandre; Delmas, Yahsou; Presne, Claire; Hamidou, Mohamed; Girault, Stéphane; Pène, Frédéric; Perez, Pierre; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Chauveau, Dominique; Ojeda-Uribe, Mario; Barbay, Virginie; Veyradier, Agnès; Coppo, Paul; Benhamou, Ygal

    2017-01-30

    Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.

  5. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Rattensperger, Dirk; Zidek, Walter

    2007-01-01

    Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy.......Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy....

  6. Cancer as an immune-mediated disease

    Directory of Open Access Journals (Sweden)

    Shurin MR

    2012-06-01

    Full Text Available Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression

  7. Guideline of Chronic Urticaria Beyond.

    Science.gov (United States)

    Fine, Lauren M; Bernstein, Jonathan A

    2016-09-01

    Urticaria is a relatively common condition that if chronic can persist for weeks, months or years and affect quality of life significantly. The etiology is often difficult to determine, especially as it becomes chronic. Many cases of chronic urticaria are thought to be autoimmune, although there is no consensus that testing for autoimmunity alters the diagnostic or management strategies or outcomes. Many times, urticaria is easily managed with antihistamines and/or short courses of oral corticosteroids, but too often control is insufficient and additional therapies must be added. For years, immune modulating medications, such as cyclosporine and Mycophenolate Mofetil, have been used in cases refractory to antihistamines and oral corticosteroids, although the evidence supporting their efficacy and safety has been limited. Omalizumab was recently approved for the treatment of chronic urticaria unresponsive to H1-antagonists. This IgG anti-IgE monoclonal antibody has been well demonstrated to safely and effectively control chronic urticaria at least partially in approximately 2/3 of cases. However, the mechanism of action and duration of treatment for omalizumab is still unclear. It is hoped that as the pathobiology of chronic urticaria becomes better defined, future therapies that target specific mechanistic pathways will be developed that continue to improve the management of these often challenging patients.

  8. The linkage between inflammation and immune tolerance: interfering with inflammation in cancer.

    Science.gov (United States)

    Rogovskii, Vladimir Stanislavovich

    2017-01-09

    Inflammation is linked to immune tolerance. In pregnancy and in immune privileged organs constitutive low-grade inflammation is required for maintaining immunological tolerance. Apart from immune tolerance in normality, there is the phenomenon of immune tolerance in cancer which mediates tumor escape from the immune system. It is widely accepted that, in many situations, chronic inflammation critically contributes to cancer. Like other types of immune tolerance, tumor-induced tolerance is also mediated by inflammation. In this review, the main mechanisms that link inflammation and tolerance are considered. We discuss drug targets that are in use to interfere with inflammation in cancer.

  9. The immune response and its therapeutic modulation in bronchiectasis.

    Science.gov (United States)

    Daheshia, Massoud; Prahl, James D; Carmichael, Jacob J; Parrish, John S; Seda, Gilbert

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.

  10. Anemia hemolítica auto-imune e outras manifestações imunes da leucemia linfocítica crônica Autoimmune hemolytic anemia and other autoimmune diseases related to chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    José O. Bordin

    2005-12-01

    Full Text Available A leucemia linfocítica crônica (LLC é freqüentemente associada a manifestações auto-imunes principalmente relacionadas às células do sistema hematopoético causando anemia hemolítica auto-imune (AHAI, púrpura trombocitopênica imune (PTI, aplasia pura de série vermelha (APSV, e neutropenia imune. A LLC é diagnosticada em até 15% dos pacientes com AHAI, e em cerca de 50% dos pacientes com AHAI secundária a doença maligna. A PTI ocorre em 2%, e a APSV em 1% dos pacientes com LLC. Prednisona é o tratamento inicial de escolha para a citopenia imune associada à LLC. Para cerca de 60% dos pacientes que apresentam recidiva da manifestação auto-imune tem sido utilizada esplenectomia, imunoglobulina endovenosa, ou ciclosporina. Embora as evidências sobre fisiopatologia sejam limitadas, os mecanismos fisiopatológicos da auto-imunidade na LLC estão relacionados à atividade dos linfócitos B leucêmicos que atuam como células apresentadoras de antígeno aberrantes, e são eficientes em processar e apresentar proteínas da membrana de hemácias e de plaquetas às células TH auto-reativas. Linfócitos TH específicos para certos auto-antígenos podem escapar de mecanismos de controle de auto-tolerância, e, se ativados, podem causar doença auto-imune. O diagnóstico de AHAI contra-indica o uso de fludarabina em pacientes com LLC, pois esse análogo da purina tem sido associado ao desenvolvimento de AHAI grave e fatal, com risco consideravelmente mais alto para pacientes mais imunossuprimidos devido a vários tratamentos anteriores.Chronic lymphocytic leukemia (CLL is frequently associated with autoimmune diseases directed against hematopoietic cells, including autoimmune hemolytic anemia (AIHA, immune thrombocytopenic purpura (ITP, pure red cell aplasia (PRCA, and immune neutropenia. CLL represents the diagnosis in up to 15% of the patients with AIHA, and in 50% of the patients with AIHA secondary to malignancy. ITP occurs in 2% and

  11. Aging changes in immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use