Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...
Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at description of ...
Tufekci, Sinan; Coban, Asuman; Bor, Meltem; Yasa, Beril; Nisli, Kemal; Ince, Zeynep
Key Clinical Message We report the occurrence of supraventricular tachycardia during intravenous immunoglobulin (IVIG) infusion. Supraventricular tachycardia was observed in two newborn patients during IVIG infusion. Both of the babies responded to adenosine treatment. Cardiorespiratory monitoring during IVIG infusion can be recommended because of the possibility of this potentially lifethreatening adverse effect.
Miqdad, A M; Abdelbasit, O B; Shaheed, M M; Seidahmed, M Z; Abomelha, A M; Arcala, O P
Although intravenous immunoglobulin G (IVIG) therapy has been reported in hyperbilirubinemia of Rh hemolytic disease, its use in ABO hemolytic disease has been reported in only a few studies. In our institute we have observed that almost 30% of babies with hyperbilirubinemia due to ABO hemolytic disease required exchange transfusion. To determine whether administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease would reduce the need for exchange transfusion as a primary goal in these babies. This was a prospective study involving all newborns with significant hyperbilirubinemia due to direct Coombs-positive ABO hemolytic disease. All healthy term babies with ABO hemolytic disease with positive direct Coombs test in the period between 2000 and 2002 were identified. Significant hyperbilirubinemia was defined as hyperbilirubinemia requiring phototherapy and/or rising by 8.5 micromol/l per h (0.5 mg/dl per h) or more to require exchange transfusion. Babies were randomly assigned into two groups: group 1 (study group) received phototherapy plus IVIG (500 mg/kg); and group 2 (control group) received phototherapy alone. Exchange transfusion was carried out in any group if at any time the bilirubin level reached 340 micromol/l (20 mg/dl) or more, or rose by 8.5 micromol/l per h (0.5 mg/dl per h) in group 2. A total of 112 babies were enrolled over 2 years, 56 in each group. Exchange transfusion was carried out in four babies in the study group, while 16 babies in the control group required exchange. Late anemia was not of concern in either group. No adverse effects related to IVIG administration were recorded. Administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb's test reduces the need for exchange transfusion without producing immediate adverse effects.
Käsermann, Fabian; Boerema, David J; Rüegsegger, Monika; Hofmann, Andreas; Wymann, Sandra; Zuercher, Adrian W; Miescher, Sylvia
It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab')(2) and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.
Full Text Available It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1 or acidified lactose (E2 were analyzed for total IgG, F(ab'(2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2; again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10% of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.
Naito, Ko-suke; Fukushima, Kazuhiro; Suzuki, Seiko; Kuwahara, Motoi; Morita, Hiroshi; Kusunoki, Susumu; Ikeda, Shu-ichi
Neuralgic amyotrophy (NA) is a distinct peripheral nervous system disorder characterized by attacks of acute neuropathic pain and rapid multifocal weakness and atrophy unilaterally in the upper limb. The current hypothesis is that the episodes are caused by an immune-mediated response to the brachial plexus, however, therapeutic strategies for NA have not been well established. We retrospectively reviewed 15 case series of NA; 10 of the 15 patients received intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy (MPPT) and 9 of these 0 patients showed clinical improvement of motor impairment. Our clinical observations do not contradict the possibility that IVIg with MPPT may be one of the potential therapeutics for NA, however the efficacy remains to be established. Further confirmatory trials are needed in patients with various clinical severities and phases of NA. Further basic research and confirmatory trials should be performed to survey the efficacy of such immunomodulation therapy for NA.
Robinson-Papp, Jessica; George, Mary Catherine; Nmashie, Alexandra; Weisz, Donald; Simpson, David M
Objective : Open-label data suggest that intravenous immunoglobulin (IVIG) might improve lower-extremity strength in human immunodeficiency virus (HIV)-associated myelopathy (HIVM), a rare but debilitating neurologic complication of HIV. We sought to determine the feasibility of testing the efficacy of IVIG for HIVM more rigorously. Design : We conducted a randomized, double-blind, placebo-controlled feasibility trial of IVIG for HIVM, using dynamometry as an outcome measure (Clinical Trial No. NCT01561755). Setting : The study took place in an academic medical center in New York, New York Participants : Only 12 participants were enrolled in four years; critical impediments to the study were the rarity of patients with new HIVM diagnoses and prior exposure to IVIG in patients with an established diagnosis. Measurements : Dynamometry of hip flexion, knee flexion, and ankle dorsiflexion were measured; the HIV Dementia Motor Score (HDMS); and the two-minute timed walk test were utilized. Results : Recruitment was the major feasibility issue. Dynamometry was generally well-tolerated, had good test-retest reliability ( r =0.71-0.86, p Dynamometry was valid and clinically meaningful based on its correlations with the HDMS and the two-minute timed walk test. Conclusion : We conclude that an adequately powered clinical trial of IVIG for HIVM would likely require a prolonged recruitment period and multiple participating sites. Lower limb dynamometry is a useful outcome measure for HIVM, which might also be useful in other HIV-related gait disorders.
Sørensen, Per Soelberg
Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...
Diemel, Robert V.; ter Hart, Hendricus G. J.; Derksen, Gerardus J. A.; Koenderman, Anky H. L.; Aalberse, Rob C.
Intravenous immunoglobulin (IVIG) products formulated as a liquid instead of a powder have become commercially available. Preferably, such liquid products should not alter after storage outside the refrigerator. Therefore, a thorough characterization of immunoglobulin G (IgG) fragmentation at
Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since
Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.
Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. Objectives To review systematically the
Sørensen, Per Soelberg
Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta......-analysis of the four trials has shown that IVIG reduces the relapse rate and, possibly, disease progression. In patients with a first episode of demyelinating disease, IVIG delays the time to the second relapse and thereby to the diagnosis of definite MS. In patients with an acute MS relapse, IVIG as add-on therapy...... to methylprednisolone does not make remission of symptoms faster or more complete. IVIG does not seem to be of any benefit to chronic visual or motor symptoms in MS. In secondary progressive MS, IVIG has not shown any effect on disease progression, relapses or new magnetic resonance imaging lesions. Experimental...
A multicentre, prospective, non-randomized, sequential, open-label trial to demonstrate the bioequivalence between intravenous immunoglobulin new generation (IGNG) and standard IV immunoglobulin (IVIG) in adult patients with primary immunodeficiency (PID).
Viallard, J-F; Brion, J-P; Malphettes, M; Durieu, I; Gardembas, M; Schleinitz, N; Hoarau, C; Lazaro, E; Puget, S
To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE ® and ClairYg ® , a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg ® . Twenty-two adult PID patients receiving stable doses of TEGELINE ® (5% lyophilized IVIG) were switched to ClairYg ® for 6 months. ClairYg ® was administered under the same conditions as TEGELINE ® , either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg ® versus TEGELINE ® . Clinical efficacy was also assessed in terms of infections and associated events. Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE ® and 9.17g/L with ClairYg ® (i.e. geometric mean for the difference between ClairYg ® and TEGELINE ® was 1.136; [90% CI: 1.092-1.181] P4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg ® . The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE ® and 4.30 [0; 15.1] for ClairYg ® . Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg ® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg ® pharmacokinetics profile was comparable to that of TEGELINE ® . ClairYg ® is safe and effective in the treatment of adult PID. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.
Duse, M; Plebani, A; Crispino, P; Ugazio, A G
Intramuscular Immunoglobulin (IMIG) have been used for 40 years in substitution therapy for antibody deficiencies and as prophylaxis for and treatment of several infectious diseases. Modified and intact intravenous immunoglobulin preparations (IVIG) have now been available for more than 10 years: only the intact product express full Fc- mediated functions with a biological half-life of IgG (3-4 weeks). These preparations have constituted an important achievement in the treatment of humoral immunodeficiencies also resulting in a dramatic improvement of the prognosis. The use of IVIG has also modified the therapeutic approach to several secondary and acquired immunodeficiencies. Treatment with IVIG for immune modulation in several diseases is investigated: substantial data indicate a useful role in selected cases of idiopathic thrombocytopenic purpura, Kawasaky disease and in some neurologic diseases. IVIG are substantially safe and severe side effects have been rarely reported.
Christiansen, O B; Larsen, E C; Egerup, P
OBJECTIVE: To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo. DESIGN: A single-centre, randomised, double-blind, placebo-controlled trial. SETTING: A tertiary...
Full Text Available Introduction: Newborn children conceived before 32 weeks of incubation are genuinely immune deficient with cord blood centralization of IgG being not as much as half contrasted with those found in infants conceived at full term. Furthermore, exceptionally preterm newborn children have lessened supplement components, polymorphonuclear chemotaxis and are obligated to debilitate their capacity pools. Aims and Objectives: This planned study has been attempted with the accompanying targets, to concentrate on the administration of IVIG in addition with antibiotics to improves the therapeutic consequence of sepsis in preterm neonates. Materials and Methods: Sixty preterm neonates with sepsis were randomly assigned into study and control groups at a tertiary level neonatal intensive care unit, Princess Esra Hospital and Owaisi Hospital & Research Centre, Deccan College of Medical Sciences, Hyderabad, Telangana, India. Study-group was given IVIG in addition to standard treatment. Results: Total 60 patients were enrolled, 30 in study and 30 in control group. There were no gender differences (male 50%, female 50% of neonates enrolled, which is also evident in the study (males 47.7%, females 52.3% and control group (males 52.3%, females 47.7%. Conclusion: Low levels of immunity in preterm neonates results in increased morbidity and mortality in severe infection. Use of IVIG along with the antibiotics and other supportive therapy can improve the outcome.
Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas
High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...
Idiopathic solar urticaria (SU) is a rare, debilitating photodermatosis, which may be difficult to treat. First-line treatment with antihistamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include plasma exchange, photopheresis and cyclosporin. We present two cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of intravenous immunoglobulin (IVIg) and have remained in remission at 13 months and 4 years, respectively. There are only two case reports of successful treatment of solar urticaria with IVIg. In our experience IVIg given at a total dose of 2 g\\/kg over several 5-day courses about a month apart is an effective treatment option for severe idiopathic SU. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis.
Intravenous immunoglobulin (IVIG) for the treatment of primary immunodeficiency disorders have been administrated for more than 25 years. However, the recognition of the anti-inflammatory and immune-modulatory actions of IVIG resulted broader applications to autoimmunity and systemic inflammatory conditions. The major focus of this review is the usefulness of IVIG therapy in children kidney disease, particularly in severe, atypical hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura, refractory to standard therapy, including plasmaferesis. The role of intravenous immunoglobulins in the treatment and prevention of infection, the most common complication in nephrotic syndrome is also discussed. Probably, in the future, similarly to adults, IVIG will be used for the therapy of some forms of glomerulopathies.
Elovaara, I.; Apostolski, S.; Doorn, P. van
Despite high-dose intravenous immunoglobulin (IVIG) is widely used in treatment of a number of immune-mediated neurological diseases, the consensus on its optimal use is insufficient. To define the evidence-based optimal use of IVIG in neurology, the recent papers of high relevance were reviewed ...
Adrichem, Max E.; Eftimov, Filip; van Schaik, Ivo N.
Intravenous immunoglobulin (IVIg) is often used as preferred treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Several studies highlighted the short-term efficacy of IVIg for CIDP yet many patients need maintenance therapy. Notwithstanding the fact IVIg has been used for
Christiansen, Ole B; Nielsen, Henriette Svarre
Immunological disturbances play a role in the majority of patients with recurrent miscarriage (RM) and therefore treatment with intravenous immunoglobulin (IvIg) has been tested in patients with RM in several trials. Seven placebo-controlled trials that were extremely heterogeneous with respect...
Harbo, T; Andersen, Henning; Hess, A
Background and purpose: For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better...... at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred. Conclusion: In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion...
Kaufman, Gabriel N; Massoud, Amir H; Dembele, Marieme; Yona, Madelaine; Piccirillo, Ciriaco A; Mazer, Bruce D
Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment.
A. I. Sushkov
Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR.
Full Text Available Although the measles vaccine has been part of routine national childhood vaccination programs throughout Europe, measles remains a public health concern. High numbers of cases and outbreaks have occurred throughout the European continent since 2011, and an increasing number of cases have been reported in Turkey since 2012. During a recent measles outbreak in Turkey, 2 pregnant women contracted measles prior to delivering preterm infants at Hacettepe University Hospital. Measles virus genomic RNA and IgM antibodies against measles were detected in the cord blood of infants and mothers in both cases. The infants were treated with intravenous immunoglobulin (IVIG and vitamin A. Transient thrombocytopenia was present in 1 infant and treated with an additional dose of IVIG and vitamin A. The infants were discharged, without complications, within 10 days of birth. The successful treatment of these cases suggests that infants who have been exposed to, or infected with, measles may benefit from cotreatment of vitamin A and IVIG.
Nasseri, Fatemeh; Mamouri, Gholam A; Babaei, Homa
To evaluate whether the use of intravenous immunoglobulin in newborn infants with isoimmune hemolytic jaundice due to Rh and ABO incompatibility is an effective treatment in reducing the need for exchange transfusion. This study included all direct Coombs' test positive Rh and ABO isoimmunized babies, who admitted in the Neonatal Intensive Care Unit of Ghaem Hospital of Mashhad University of Medical Sciences, Iran, from October 2003 to October 2004. Significant hyperbilirubinemia was defined as rising by >or=0.5 mg/dl per hour. Babies were randomly assigned to received phototherapy with intravenous immunoglobulin (IVIg) 0.5 g/kg over 4 hours, every 12 hours for 3 doses (study group) or phototherapy alone (control group). Exchange transfusion was performed in any group if serum bilirubin exceeded >or=20mg/dl or rose by >or=1mg/dl/h. A total of 34 babies were eligible for this study (17 babies in each group). The number of exchange transfusion, duration of phototherapy and hospitalization days, were significant shorter in the study group versus control group. When we analyzed the outcome results in ABO and Rh hemolytic disease separately, the efficacy of IVIg was significantly better in Rh versus ABO isoimmunization. Late anemia was more common in the IVIg group 11.8% versus 0%, p=0.48. Adverse effects were not observed during IVIg administration. Administration of IVIg to newborns with significant hyperbilirubinemia due to Rh hemolytic disease reduced the need for exchange transfusion but in ABO hemolytic disease there was no significant difference between IVIg and double surface blue light phototherapy.
Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.
Ye, Y; Li, S-L; Li, Y-J
To observe and compare the clinical curative effect of the plasma exchange (PE) and intravenous immunoglobulin (IVIg) for Guillian-Barre Syndrome (GBS). Overall, 64 adult patients with GBS for PE and IVIg treatment, respectively, and nerve function were observed pre-treatment and at 1 week/2 weeks after completion of treatment; the blood immunoglobulin, complement, fibrinogen (Fib) and monocyte percentage (MON%) were detected simultaneously. After PE treatment, nerve function defect appeared to improve better than the IVIg group and clinical effect was better than the IVIg group. Treatment effective rates of the two groups after 2 weeks, respectively, are 96 and 79%. PE and IVIg can significantly reduce the GBS patients' blood immunoglobulin IgG, IgA, IgM, C3 and C4, but these were significantly lower in the PE group than in the IVIg group. Fib and MON% were significantly lower in the PE group than in the IVIg group. Both PE and IVIg have a high response as therapy and are reasonable therapeutic options for GBS. However, PE treatment has a more significantly curative effect, as it can effectively improve symptoms and be helpful in the early rehabilitation of patients. © 2014 British Blood Transfusion Society.
Full Text Available Abstract Background Multiple system atrophy (MSA is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG in MSA. Methods This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Results Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p Conclusions Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.
Beken, Serdar; Hirfanoglu, Ibrahim; Turkyilmaz, Canan; Altuntas, Nilgun; Unal, Sezin; Turan, Ozden; Onal, Esra; Ergenekon, Ebru; Koc, Esin; Atalay, Yildiz
Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. ...
Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut
This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment.
Full Text Available Transient hypogammaglobulinemia of infancy (THI is characterized by recurrent infections and one or more reduced serum immunoglobulin levels. Typically, THI patients recover spontaneously, mostly within 30-40 months of age, but sometimes recovery may be delayed until 5-6 years of age. The use of intravenous immunoglobulin (IVIg as an alternative to antibiotic prophylaxis remains contraversial also in symptomatic THI patients. In fact, some authors believe that IVIg therapy may cause a delay in the maturation of the humoral immune system because of the interference from passively transfered antibodies. The aim of this study was to investigate the effect of IVIg replacement on recovery from immunodeficiency in THI patients and determine new parameters in order to include these patients in IVIg therapy groups. In this retrospective study, 43 patients (65% received IVIg replacement therapy while 23 patients (34.8% showed spontaneous normalization without IVIg. The percentages of patients who had more than six times the number of febrile infections in a year decreased from 91% to 21% in the group receiving IVIg treatment. At admission, before being recruited to IVIg therapy, serum immunoglobulin G (IgG levels and anti-hemophilus B (Hib antibody titers were found to be significantly low in cases who were selected for IVIg replacement. The percentages of patients who did not have protective levels of anti-Hib, anti-rubella or anti-rubeola-IgG were also significantly high in IVIg cases. There was no statistically significant difference in the age at which IgG levels normalized between the IVIg and the non-IVIg group. Patients in the IVIg group and non-IVIg group reached normal IgG levels at the age of 42.9±22.0 and 40.7±19.8 months, respectively. In conclusion, IVIg infusions do not cause a delay in the maturation of the immune system in THI patients. Besides the well-established criteria, very low and non-protective specific antibody responses
Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y
The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.
Loomba, Rohit S; Raskin, Alexander; Gudausky, Todd M; Kirkpatrick, Edward
Early treatment with intravenous immunoglobulin (IVIG) is necessary to help reduce the risk of coronary artery abnormalities, such as coronary artery aneurysms and to help alleviate symptoms, in Kawasaki disease. Some patients, however, do not respond to an initial dose of IVIG and require additional doses. Prediction of these IVIG nonresponders may be of assistance in altering initial therapy to make it more effective. The Egami score has been validated in the Japanese population to predict IVIG nonresponders but has shown to be ineffective in US populations. This study evaluates the Egami score in a Midwest US population, subdividing patients by race and the diagnosis of typical or atypical type of Kawasaki disease. Patients were included in the study if they met criteria for Kawasaki disease and received IVIG in the inpatient setting. A total of 182 patients were studied, and in all studied groups, the Egami score had poor sensitivity at predicting IVIG nonresponders. Sensitivity of the score differed between races and differed between typical and atypical Kawasaki disease. The Egami score, as well as other systems, have been validated to predict IVIG nonresponders. These, however, lack sensitivity in the US population. Other scores developed in the United States have also lacked sensitivity, likely due to the absence of race or Kawasaki disease classification as variables. The development of a sensitive scoring system to predict IVIG nonresponders in US populations will require the incorporation of race and Kawasaki disease classification, factors that seem to alter IVIG response.
Teo, L; Tay, Y K; Liu, T T; Kwok, C
Toxic epidermal necrolysis (TEN) is a rare, severe adverse drug reaction. Steven-Johnson syndrome (SJS) represents the milder end of the spectrum. The exact pathogenesis of TEN and SJS is still unknown and many drugs, including prednisolone, cyclosporin and intravenous immunoglobulin (IVIG), have been used in an attempt to halt the disease process. The use of IVIG in particular is controversial. We share our experience with the use of IVIG in six patients with TEN. We will also review the various proposed mechanisms underlying TEN, the mechanism of action of IVIG in TEN and summarise useful treatment options.
Shanbag, Preeti; Amirtharaj, Cynthia; Pathak, Ashish
This is a retrospective analysis of 25 children with severe Guillain-Barre syndrome admitted to our PICU. All children were treated with intravenous immunoglobulins (IVIG) in a dose of 2 g/kg body weight over 2-5 days in addition to supportive and respiratory care. Seventeen children were elective admissions to the PICU whereas 8 children were transferred from other hospitals in a critical condition. Five of 8 of the late referrals died as compared to none of the elective admissions. All 8 of the late referrals required mechanical ventilation as against 3 of the 17 elective admissions. Mean duration of PICU stay in the late referrals was 27 days as compared to 15 days in the elective admissions. The authors concur with previously published reports, that early use of IVIG could reduce the mortality and the need for intubation and mechanical ventilation.
Bayry, Jagadeesh; Lacroix-Desmazes, Sébastien; Kazatchkine, Michel D; Kaveri, Srini V
The dramatic increase in both the number of novel infectious agents and resistance to antimicrobial drugs has incited the need for adjunct therapies in the war against infectious diseases. Exciting recent studies have demonstrated the use of antibodies in the form of intravenous immunoglobulin (IVIg) against infections. By virtue of the diverse repertoire of immunoglobulins that possess a wide spectrum of antibacterial and antiviral specificities, IVIg provides antimicrobial efficacy independently of pathogen resistance and represents a promising alternative strategy for the treatment of diseases for which a specific therapy is not yet available.
Full Text Available Mohamed Mahdi-Rogers, Yusuf A RajaballyNeuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester, UKAbstract: Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg.Keywords: chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulin, pathogenesis, treatment
David J Lederer
Full Text Available We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG after lung transplantation.We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG, 10% Purified (Gamunex, Bayer, Elkhart, IN monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG. The primary outcome was the number of bacterial infections within each treatment period.IVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24. There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001. Four serious adverse events (resulting in hospitalization occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37. Chills, flushing, and nausea occurred during one infusion of IVIG.Treatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown.Clinicaltrials.gov NCT00115778.
Jôice Dias Corrêa
Full Text Available Intravenous immunoglobulin (IVIG is used in the treatment of neuropathy. This case report presents, for the first time, a patient with severe periodontal destruction after chronic therapy with IVIG. The patient reported having extracted his maxillary anterior teeth himself due to high mobility. Clinical examination and radiographic images show a generalized and severe periodontitis. No significant alterations in genetic or microbiological features were observed. The present case suggests that periodontal disease aggravation could be considered a new adverse effect of IVIG therapy. Postulated mechanisms are immune complexes formation, complement activation, and a direct effect in osteoclasts. In conclusion, it is important that patients that will receive IVIG treatment underwent dental evaluation.
Lyubomir A. Dourmishev
Full Text Available Intravenous immunoglobulins (IVIGs, a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies, as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.
Knudsen, S; Mikkelsen, J D; Bang, B
Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....
Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco
The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.
Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues
Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.
Hyo Min Park
Full Text Available <b>Purpose:</b> It has been reported that 10% to 20% of children with Kawasaki disease (KD will not respond to intravenous immunoglobulin (IVIG treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. <b>Methods:</b> We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. <b>Results:</b> Among the 309 children, 30 (9.7% did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT, total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. <b>Conclusion:</b> Two independent predictors (ALT?#248;4 IU/L, total bilirubin?#240;.9 mg/dL for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.
Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James
A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.
Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L
In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.
Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares
Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist
Papagianni, Andromachi; Economou, Marina; Tragiannidis, Athanasios; Karatza, Eliza; Tsatra, Ioanna; Gombakis, Nikolaos; Athanassiadou-Piperopoulou, Fani; Athanasiou-Metaxa, Miranda
We conducted a study to evaluate the efficacy of intravenous (IV) anti-D against IV immunoglobulin (IVIG) in newly diagnosed immune thrombocytopenia (ITP) in children and to identify the clinical characteristics of the children most likely to benefit from one or the other treatment. Children (6 mo to 14 y) with newly diagnosed ITP and a platelet count D or with 0.8 to 1 g/kg IVIG in a randomized manner. Twenty-five patients, mean age of 6.8 years, were treated either with IV anti-D (n=10) or with IVIG (n=15). Both drugs were equally efficient in raising the platelet count above 20,000/μL at 24 hours posttreatment. Children who presented with bleeding stage 1 or 2 (no mucosal bleeding) responded better to IVIG treatment, in terms of an increase in platelet count at 24 hours posttreatment (P=0.04). Hemoglobin drop was greater in the anti-D group (P=0.002). A single bolus dose of 50 μg/kg of IV anti-D is a safe and effective first-line treatment in newly diagnosed ITP in childhood and mucosal bleeding is a poor prognostic factor for treatment with IVIG.
A comparison of intravenous immunoglobulin (2 g/kg totally) and single doses of anti-D immunoglobulin at 50 μg/kg, 75 μg/kg in newly diagnosed children with idiopathic thrombocytopenic purpura: Ankara hospital experience.
Alioglu, Bulent; Ercan, Sirma; Tapci, Ayse Esra; Zengin, Tugba; Yazarli, Esra; Dallar, Yildiz
We conducted this prospective randomized trial of intravenous immunoglobulin (IVIG) treatment in children with newly diagnosed immune thrombocytopenic purpura (ITP) to compare the efficacy of IVIG to standard and higher doses of anti-D IVIG. Seventy-eight patients who were previously untreated and between the age of 1 and 18 years with newly diagnosed acute ITP and a platelet concentration less than 20×10/l were eligible for enrollment. In this study IVIG treatment was compared with two different doses of anti-D. Study patients were randomized to receive treatment according to one of the two single anti-D IVIG doses [50 μg/kg (n=19) or 75 μg/kg (n=20)] or 2 g/kg (400 mg/kg per day, 5 day) total dose of IVIG (n=39). There is a significant increase of 24th hour, 48th hour, 72nd hour, 7th day and 30th day platelet counts in IVIG (2 g/kg, total dose) group compared to anti-D IVIG 50 μg/kg and anti-D IVIG 75 μg/kg groups. However, there were no difference between 24th hour, 48th hour, 72nd hour, 7th day and 30th day platelet counts across anti-D IVIG 50 μg/kg and anti-D IVIG 75 μg/kg groups. In conclusion, this study suggests that IVIG is well tolerated and significantly more effective than standard and high-dose anti-D IVIG for the treatment of newly diagnosed ITP in children. Apart from this, we believe that IVIG might be the first-line treatment of these patients. Regarding this issue further prospective studies comparing different IVIG treatment regimens with anti-D IVIG treatment regimens are needed.
Meer, J.W. van der; Beem, R.T. van; Robak, T.; Deptala, A.; Strengers, P.F.W.
BACKGROUND AND OBJECTIVES: In the production process of a new 5% liquid intravenous immunoglobulin (IVIG-L) product (Nanogam((R)) ), a combined pepsin/pH 4.4 treatment/15-nm filtration (pH 4.4/15NF) step and a solvent-detergent (SD) treatment step were incorporated to improve the virus
The efficacy of the prophylactic use of intravenous immunoglobulin (Ig) was evaluated in a double-blind placebo-controlled trial of 21 pairs of ventilated neonates weighing more than 1 500 g, Each infant received 0.4 g/kglday of intravenous Ig or a similar volume of placebo daily for 5 days. Criteria used to assess the ...
Anh-Tu Hoa, Sabrina; Hudson, Marie
The aim of this review was to summarize key findings from the literature concerning the therapeutic role of intravenous immunoglobulins (IVIg) in idiopathic inflammatory myopathies (IIM), dissecting the evidence according to disease subtype and treatment indication, and to review the evidence relating to the mechanism of action of IVIg in IIM to ascertain rationale for continued research. Medline (Ovid) and Pubmed databases were searched from inception to July 2016 using relevant keywords. Original and review articles were retrieved for full-text review. Bibliographies of selected articles were also hand-searched for additional references. Data were summarized qualitatively and in tabular form. The efficacy of IVIg in IIM is supported by 3 randomized controlled trials, involving dermatomyositis and polymyositis subjects, in refractory, relapsed, or steroid-dependent disease, as well as part of first-line therapy in elderly dermatomyositis subjects. Other indications for IVIg are supported by uncontrolled evidence only. Limitations of studies include open, uncontrolled or retrospective study designs, small and selected samples, short-term follow-up and ad hoc outcome measures. Despite the limited evidence, there is strong biological plausibility for the role of IVIg in IIM. Robust, controlled evidence to support the use of IVIg using validated outcome measures is urgently required to guide therapeutic decision-making and maximize outcomes in IIM. Copyright © 2017 Elsevier Inc. All rights reserved.
Barbaud, A; Tréchot, P; Granel, F; Lonchamp, P; Faure, G; Schmutz, J L; Béné, M C
Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.
Shayan, Gilda; Adamiak, Basia; Relkin, Norman R.; Lee, Kelvin H.
Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer’s disease (AD). In this study, a Random Forest classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before the therapy, after six months of therapy, and after a three-month drug washout period. Samples were analyzed using two-dimensional gel electrophoresis and further studied using a Random Forest classification model to identify effects of IVIg on a panel of 23 putative diagnostic AD biomarkers previously identified. Six of the eight subjects showed improvements with respect to the 23 AD diagnostic biomarkers after six months of therapy compared to the samples taken at the outset of the trial. All subjects reverted back to baseline during drug washout. These results are also consistent with clinical observations. The observed improvements in subjects during six months of IVIg therapy and the reversion back to baseline during drug washout provides preliminary evidence regarding the potential use of IVIg as an AD immunotherapy. PMID:22806462
Modrof, Jens; Tille, Björn; Farcet, Maria R; McVey, John; Schreiner, Jessica A; Borders, Charles M; Gudino, Maria; Fitzgerald, Peter; Simon, Toby L; Kreil, Thomas R
We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: email@example.com.
Full Text Available Background: Drug use evaluation (DUE aims at improving the patients’ care. Studying the administration pattern of intravenous immunoglobulin (IVIG is an important research topic due to its significant role in the treatment and controlling of many disorders, high prices, and limited availability of this drug. Methods:This observational cross-sectional study was conducted at Shahid Sadoughi Hospital in Yazd, central Iran, from May to September 2014. The orders of different wards in the hospital for IVIG given to the hospital central pharmacy were surveyed. Also, a special form developed for evaluation the method of administration. The related physician and nurse were consulted on drug complications and the causes. Finally, the gleaned data were compared to the available standards on the prescription and administration of IVIG.Results:A total of 75 patients received IVIG during this study. 58.7% of the prescriptions belonged to the cases approved by Food and Drug Administration (FDA. The most frequent cause of the use of IVIG was idiopathic thrombocytopenic purpura (ITP. The rate and dose of administration was suitable in most of the patients, yet, the measurement of laboratory parameters required for IVIG were observed in only a few cases. Complications occurred in 26.7% of the patients receiving it, which was mostly related to infusion-related reactions. On the whole, 3922 g IVIG was used during this study of which 1848 g belonged to the cases approved by FDA.Conclusion:Regarding the high costs of IVIG, complications, and limited information on the quality of the effect of this drug in the treatment of many cases, physicians should be cautious enough with its appropriate use. Besides, the presence of a clinical pharmacist in the health-care team not only improves the quality of drug therapy and treatment results, but also plays an important part in decreasing the treatment costs for the patients.
Imazio, Massimo; Lazaros, George; Picardi, Elisa; Vasileiou, Panagiotis; Carraro, Mara; Tousoulis, Dimitrios; Belli, Riccardo; Gaita, Fiorenzo
Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400-500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ~3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.
Matsuura, Ryuki; Hamano, Shin-Ichiro; Hirata, Yuko; Oba, Atsuko; Suzuki, Kotoko; Kikuchi, Kenjiro
To evaluate factors influencing the efficacy and safety of intravenous immunoglobulins (IVIG) therapy for West syndrome. We investigated seizure outcomes in 70 patients who received IVIG treatment for West Syndrome during the first 3months after the onset of epileptic spasms. IVIG was administered for 3 consecutive days (initial IVIG treatment) at dosages ranging from 100 to 500mg/kg/day. If spasms disappeared within 2weeks of the initial treatment, maintenance IVIG treatment was commenced. We evaluated seizure outcomes at 2weeks (initial evaluation), at 2years (long-term evaluation), and the last visit (last follow-up evaluation) after the initial IVIG treatment. We analyzed dosages of IVIG, age at onset of spasms, treatment lag, and etiologies between responders and non-responders. Among the patients, 7/70 (10.0%) had cessation of spasms and resolution of hypsarrhythmia at the initial evaluation. Another 6/70 patients (8.6%) were found to have cessation of spasms at the long-term evaluations. The treatment lag in responders was shorter than that in non-responders (PWest syndrome. IVIG therapy has a good safety profile and we would recommend it for West syndrome cases with drug resistance, severe complications associated with profound brain damage, severe brain atrophy, and in immunocompromised patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Zeiler, F A; Matuszczak, M; Teitelbaum, J; Kazina, C J; Gillman, L M
Our goal was to perform a scoping systematic review of the literature on the use of intravenous immunoglobulins (IVIG) for refractory status epilepticus (RSE) in adults. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. Twenty-four original articles were identified. A total of 33 adult patients were described as receiving IVIG for RSE. Seizure reduction/control with IVIG occurred in 15 of the 33 patients (45.4%), with 1 (3.0%) and 14 (42.4%) displaying partial and complete responses respectively. No adverse events were recorded. Oxford level 4, GRADE D evidence exists to suggest an unclear impact of IVIG therapy in adult RSE. Routine use of IVIG in adult RSE cannot be recommended at this time. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Brazzelli, V; Grassi, S; Savasta, S; Ruffinazzi, G; Carugno, A; Barbaccia, V; Marseglia, G L; Borroni, G
Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial etiology, including genetic determinants, allergy to metals, and id reaction; rarely it is a drug-related side effect. We report a paediatric case of pompholyx of the hands related to the intravenous immunoglobulin (IVIG) therapy for Clinically Isolated Syndrome (CIS). A 10-year-old boy, received an IVIG therapy (Venital, Kedrion Spa, Italy) at a dose of 400 mg/kg daily for five days. The fifth day of IVIG infusion, a symmetrical vesicular eruption appeared on the palms of the hands and on lateral aspects of the fingers. The lesions improved with application of topical steroids in few days. The mechanism of induction of pompholyx by IVIG therapy is unknown. A review of the Literature suggests the hypothesis that dyshidrotic eczematous reactions may be related not only to the type of IVIG, to the dose and the rates of infusion, but also to an allergic response to excipients and preservatives contained in the drug, probably elicited by an underlying neurological disease in some cases.
Full Text Available Background Kawasaki Disease (KD is a vasculitis with multi-organ involvementof unknown etiology; it is the most common cause of pediatric-heart diseases in developed countries. Treatment with Intravenous Immunoglobulin (IVIG prevents coronary artery lesions; although there are some IVIG-resistant cases, combination therapy with corticosteroids and IVIG is one of the recommendations for treatment of these cases. The aim of this study was to compare these three options for treatment of Kawasaki Disease and to evaluate their ability to deal with coronary artery complication of Kawasaki Disease. Materials and Methods A prospective cross- sectional study of hospitalized cases of Kawasaki Disease, conducted in pediatric department of Imam Reza hospital, Mashhad-Iran, during 2013 to 2015 (18 months. Based on demographic and clinical data of these patients, children with high risk of unresponsiveness to IVIG therapy (based on Harada score, were determined and treated with IVIG and corticosteroids- combination initially. Follow-up patients for heart complications were 6 weeks. Results Twenty five patients (89.2% out of total 28 hospitalized patients in this period of time who fulfilled diagnostic criteria were considered as complete Kawasaki Disease. Coronary Artery Lesions (CALs were shown in 4 patients during the follow-up period, with high risk in patients with incomplete presentation (33.3% versus 12%, P
Christelle M Ilboudo
Full Text Available Intravenous immunoglobulin (IVIG is commonly used for a wide range of diagnoses, by multiple pediatric subspecialists. We report two cases of hepatitis B screening results post IVIG infusion, where positive anti-Hepatitis B core antigen serology tests indicated possible occult hepatitis infection, leading to a delay in care. However, serial antibody testing showed results consistent with the passive transfer of antibodies.
Kuo, Ho-Chang; Wong, Henry Sung-Ching; Chang, Wei-Pin; Chen, Ben-Kuen; Wu, Mei-Shin; Yang, Kuender D; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei-Chiao
Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively). This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG. © 2017 The Authors.
Tenti, Sara; Cheleschi, Sara; Guidelli, Giacomo Maria; Galeazzi, Mauro; Fioravanti, Antonella
The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses and recurrent fetal losses, frequently accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or anti-β2 glycoprotein-I (β2GPI) antibodies. The current mainstay of treatment for thrombotic APS is heparin followed by long-term anticoagulation, while in obstetric APS, the accepted first-line treatment consists in low-dose aspirin (LDA) plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). Recently, new emerging treatment modalities, including intravenous immunoglobulins (IVIG), have been implemented to manage APS refractory to conventional therapy. The objective of this review is to summarize the currently available information on the IVIG therapy in APS, focusing on the use of IVIG in the obstetric form, CAPS and on primary or secondary thromboprophylaxis. We analyzed 35 studies, reporting the effects of IVIG in APS patients, and we discussed their results. IVIG in obstetric APS seem to be very useful in selected situations (patients not responsive to the conventional treatment, concomitant autoimmune manifestations or infections or patients in whom anticoagulation is contraindicated). IVIG treatment represents an important component of the combination therapy of CAPS and they could be useful, in addition to the standard therapy, to prevent recurrent thrombosis in APS patients refractory to conventional anticoagulant treatment. Anyway, in some cases we also found controversial results that claim the need of further well-designed studies to definitely state the efficacy and tolerability of IVIG in CAPS, obstetric and non-APS. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available Japanese encephalitis (JE virus (JEV is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group died during treatment and two (placebo subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2, which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.ClinicalTrials.gov NCT01856205.
Nieminen, U.; Syrjaelae, M.; Ikkala, E.; Myllylae, G.
The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with /sup 111/In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.
del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime
Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.
Markvardsen, Lars Høj; Harbo, Thomas; Christiansen, Ingelise
performed before and two weeks after infusion of IVIg. Following treatment blood haemoglobin declined from 8.6±0.8 to 8.1±1.3mmol/l, p... naive patients are susceptible to develop haemolysis. Haemolytic anaemia is a severe side effect that seems to be more frequent after immunoglobulin infusions than previously recognized....
Lee, Soyoung; Kim, Han Wool; Kim, Kyung Hyo
The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888-8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438-965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.
Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman
Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.
José, Marta; Marzo, Núria; Pons, Berta; Herrerias, Aida; López, Laura; Faro, Merche; López, Maite; Jorquera, Juan I
Studies have demonstrated that traces of activated factor XI (FXIa) present in specific brands of intravenous immunoglobulin (IVIG) concentrates may pose a thrombogenic risk. To characterize procoagulant activity during fractionation and the elimination capacity of the Flebogamma(®) DIF (Grifols' IVIG) manufacturing process. Flebogamma(®) DIF fractionation steps included cryoprecipitate supernatant (Cryo/S), Fraction (Fr) I supernatant, and Fr II + III suspension. Purification steps included ultrafiltrate I, acid treatment, and pasteurization. Samples were assessed for total protein, IgG, and procoagulant activation markers. Cryo/S showed no procoagulant activity for prekallikrein activator (PKA), kallikrein-like, and non-activated partial thromboplastin time (NaPTT) with normal (-PPP) or FXI-deficient (-FXI) platelet poor plasma. Thrombin generation test (TGT)-PPP and TGT-FXI were DIF production process is capable of eliminating procoagulant activity because of its purification steps. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Beken, Serdar; Hirfanoglu, Ibrahim; Turkyilmaz, Canan; Altuntas, Nilgun; Unal, Sezin; Turan, Ozden; Onal, Esra; Ergenekon, Ebru; Koc, Esin; Atalay, Yildiz
Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. Infants were divided into two groups: Group I (n = 71) received one dose of IVIG (1 g/kg) and LED phototherapy whereas Group II (n = 46) received only LED phototherapy. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3.1 ± 1.3 days in Group I and 2.27 ± 0.7 days in Group II (p hemolytic disease. Meticulus follow-up of infants with ABO hemolytic disease and LED phototherapy decreases morbidity. IVIG failed to show preventing hemolysis in ABO hemolytic disease.
Asghar, S.P.; Mubarik, H.
Objective: To compare the therapeutic outcomes of plasmapheresis with intravenous immunoglobulins (IVIG) for Guillain Barre syndrome. Study Design: Randomized controlled trial. Place and Duration of Study: Medicine department; PNS Shifa Hospital Karachi from Jan 2011 to Jun 2012. Patients and Methods: Adult patients admitted to internal medicine department with the diagnosis of Guillain Barre Syndrome (GBS) fulfilling the inclusion and exclusion criteria were included after taking ethical approval and informed consent. They were randomly assigned to plasmapheresis and IVIG treatment groups. Their presenting features, investigations and management plan were followed over 6 months duration. Hughes disability scale for Guillain Barre syndrome was documented and compared at admission, 4 weeks, 12 weeks and 6 months by non-parametric tests via SPSS version 17. Results: Total 36 patients (31 males and 5 females) were included. Mean age was 37 ± 15 (18-70) years, mean duration of symptoms 11.6 ± 12.7 days. Plasmapheresis and IVIG groups were comparable with respect to age and gender (p>0.05). Significant improvement of mean disability score was observed in each group from baseline score (p<0.0005). At specified intervals, comparison between the two groups in terms of mean improvement in disability scores showed significant improvement at 4 weeks (p<0.05) in IVIG group as compared to plasmapheresis group; however on further observation at 12 weeks and 6 months, mean improvement was comparable between two groups with no significant difference (p>0.05). There was no significant difference in need for assisted ventilation between two groups (p>0.05). Variants of GBS observed were AIDP (50%), AMAN (31%) and AMSAN (19%). Conclusion: Our study suggests that both plasmapheresis and intravenous immunoglobulins are useful and effective modes of treatment for Guillain Barre Syndrome. Significant short term improvement was observed in the IVIG group at 4 weeks of treatment; however
Full Text Available Michael F Diejomaoh,1,2 Zainab Bello,2 Waleed Al Jassar,1,2 Jiri Jirous,2 Kavitha Karunakaran,2 Asiya T Mohammed11Department of Obstetrics and Gynaecology, Faculty of Medicine, Kuwait University, Safat, 2Maternity Hospital, Shuwaikh, Kuwait Background: Recurrent spontaneous miscarriage (RSM has a multifactorial etiology, mainly due to karyotype abnormalities including balanced translocation, anatomical uterine disorders, and immunological factors, although in 50%–60% the etiology is unexplained. The treatment of RSM remains challenging, and the role of intravenous immunoglobulin (IVIG in RSM is controversial. Case report: Mrs HM, 37 years old, obstetric summary: P0+1+13+1, a known case of hypothyroidism/polycystic ovary syndrome, married to an unrelated 47-year-old man, presented to our RSM clinic in early January 2014 for investigation and treatment. She has had multiple failed in vitro fertilization trials and 13 first-trimester missed miscarriages terminating at 6–7 weeks, all without IVIG therapy. Her tenth pregnancy was spontaneous, managed in London, UK, with multiple supportive therapy and courses of IVIG starting from the third to the 30th week of pregnancy. The pregnancy ended at 36 weeks of gestation with a cesarean section and a live girl baby was delivered. Mrs HM had balanced translocation, 46XX t (7:11 (p10:q10. Preimplantation genetic diagnosis/intracytoplasmic sperm injection/in vitro fertilization was performed with embryo transfer on May 29, 2014, and resulted in a successful pregnancy. She was commenced immediately on metformin, luteal support, and IVIG therapy, started at 6 weeks of gestation and at monthly intervals until 30 weeks of gestation, and also received additional therapy. The pregnancy was monitored with ultrasound, progressed uneventfully until admission at 35 weeks of gestation, with mildly elevated liver enzymes and suspected fetal growth restriction. She was managed conservatively, and in the light of
Bharath, Vighnesh; Eckert, Kathleen; Kang, Matthew; Chin-Yee, Ian H; Hsia, Cyrus C
Aseptic meningitis is a rare but significant complication of intravenous immunoglobulin (IVIG) therapy. The majority of literature is limited to case reports, so the true incidence of this complication is uncertain. A retrospective review of all cases of IVIG-associated adverse transfusion reactions was performed at London Health Sciences Centre (LHSC) from January 1, 2008, to December 31, 2013. All reported transfusion reactions were evaluated to identify cases of aseptic meningitis due to IVIG. All documented IVIG infusions and lumbar punctures performed during the study period were reviewed; patients with both interventions were identified and further chart review was performed to identify aseptic meningitis. During our study period, 1324 unique patients received a total of 11,907 IVIG infusions (554,566 g) for various conditions. Eight cases of aseptic meningitis were identified, suggesting an overall incidence of 0.60% for all patients and 0.067% for all IVIG infusions. Patients presented with symptoms within 24 to 48 hours of the infusion and were treated with antibiotics initially. The reactions were self-limited, as symptoms self-resolved within 5 to 7 days. Treatment was supportive, with subsequent IVIG infusions likely requiring preinfusion medication or possibly a switch in product formulation. This review of IVIG-induced aseptic meningitis over a 6-year period identifies a more robust estimate of incidence and risk of 0.60% and 0.067% for all patients and infusions, respectively. Given that this complication can mimic infectious meningitis and cause considerable morbidity, physicians need to be aware of this rare but important condition. © 2015 AABB.
Venkataraman, Rohini; Yusuf, Kamran
Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen. We report, a multiparous female whose pregnancy was complicated by HDN due to anti-SARA antibodies requiring both exchange transfusion and intravenous immunoglobulin. The response was sustained after intravenous immunoglobulin (IVIG) rather than after exchange transfusion.
Egger, M; Prüller, F; Raggam, R; Divjak, M K; Kurath-Koller, S; Lackner, H; Urban, C; Strenger, V
(1-3)-ß-D-Glucan (BDG) is a marker for invasive fungal diseases (IFD). Administration of intravenous immunoglobulin preparations (IVIG) has been reported to lead to false positive BDG serum levels >80 pg/ml. The aim of the study was to determine the time interval between IVIG infusion and normalisation of BDG serum levels. In 22 paediatric haemato-/oncologic patients, we analysed 92 BDG serum levels obtained within 4 weeks after IVIG administration (0.5 to 1 g/kg body weight), correlated them to 54 IVIG episodes and compared them to 76 BDG levels obtained in 29 patients without IVIG administration in the 4 weeks prior to BDG analyses (control group). BDG peak levels within 3 days after IVIG ranged from 21.47 to 660.38 (median 201.4) pg/ml. BDG serum levels at 7, 14 and 21 days (+/-1 day each) after IVIG infusion were significantly higher than BDG serum levels in the control group (p < 0.001 each). By days 7, 14, and 21 (+/-1 day each) after IVIG infusion, BDG serum levels have normalized (<80 pg/ml) in 64.0%, 76.5% and 100%, respectively. IVIG administration leads to false positive BDG levels in the vast majority of patients. Elevated BDG levels may be detectable for more than two weeks after IVIG administration, while BDG levels normalized within 3 weeks in all patients. Therefore, BDG should not be used to diagnose IFD within three weeks after IVIG administration. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Akman, Alkim Oden; Kara, Fatma Karaca; Koksal, Tulin; Cakir, Bahar Cuhaci; Karagol, Cuneyt; Sayli, Tulin
Immunoglobulin therapy can be used to treat a wide variety of diseases. However, intravenous immunoglobin products can cause several adverse reactions, including hemolysis. The objective of this study was to determine the extent of anemia and hemolysis after high dose intravenous immunoglobin (2g/kg) and its relationship to the ABO blood type system and hemolytic anemia blood parameters in pediatric patients. Incidence of 'Intravenous immunoglobulin related hemolysis' was %19 (6/31) after high dose intravenous immunoglobulin therapy. The blood parameters were measured before IVIG infusion (1-24h before infusion) and 3-10 days after the first day of infusion. In terms of decrease in Hb levels; decline of 2g/dL (severe hemolysis) in 4 patients (12.9%) after infusion. The decrease in hemoglobin, haptoglobin levels, the increase of reticulocyte count or direct bilirubin were statistically significant after infusion. Five of 6 hemolysis patients had non-O blood group, however statistically significant difference was not noted between these two groups. Also, intravenous immunoglobulin-related hemolysis was determined significantly higher in female than male patients. Mild to moderate hemolysis may be undetected after infusion and the true incidence of such reactions is difficult to document without careful clinical and laboratory follow-up. A careful risk assessment analysis should be performed before intravenous immunoglobulin infusion. Copyright © 2017 Elsevier Ltd. All rights reserved.
Kuo, Ho-Chang; Hsu, Yu-Wen; Wu, Mei-Shin; Chien, Shu-Chen; Liu, Shih-Feng; Chang, Wei-Chiao
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and it is therefore worth examining the multifactorial interaction of genes and environmental factors. Targeted genetic association and genome-wide association studies have helped to provide a better understanding of KD from infection to the immune-related response. Findings in the past decade have contributed to a major breakthrough in the genetics of KD, with the identification of several genomic regions linked to the pathogenesis of KD, including ITPKC, CD40, BLK, and FCGR2A. This review focuses on the factors associated with the genetic polymorphisms of KD and the pharmacogenomics of the response to treatment in patients with intravenous immunoglobulin resistance. Copyright © 2014. Published by Elsevier B.V.
Full Text Available Impetigo herpetiformis (IH, if left untreated, is associated with a high rate of perinatal morbidity and mortality and may lead to the decision of termination of pregnancy. There are various and effective therapeutic agents available for the treatment of the disease. A 23-year-old woman with a history of plaque psoriasis presented with a sudden generalized pustular eruption on the 25th week of her first gestation. The diagnosis was made based on the clinical and histopathological findings. The patient was treated with systemic prednisolone (2 mg/kg/d first and, cyclosporine A (3 mg/kg/d was added to the treatment after two weeks because prednisolone was not effective alone. The lesions did not regress despite four weeks of combined treatment with prednisolone and cyclosporine. Intravenous immunoglobuline (IVIG (0.3 g/kg/d, 6 days was added on the 30th week of gestation and resulted in regression of cutaneous rashes. On the 33rd week of gestation, IVIG (0.7 g/kg/d, 3 days was repeated due to reactivation of pustules, and an improvement was observed. In this case report, we called attention to IVIG therapy in IH, for having the pregnancy continued enough for the fetal maturation before the delivery.
van der Meer, J W M; van Beem, R T; Robak, T; Deptala, A; Strengers, P F W
In the production process of a new 5% liquid intravenous immunoglobulin (IVIG-L) product (Nanogam(®) ), a combined pepsin/pH 4·4 treatment/15-nm filtration (pH 4·4/15NF) step and a solvent-detergent (SD) treatment step were incorporated to improve the virus inactivating/reducing capacity of the manufacturing process. Two prospective uncontrolled multicentre studies were performed to evaluate the safety and efficacy of this product. Efficacy, including pharmacokinetics, of IVIG-L was studied for 6 months in 18 primary immunodeficiency (PID) patients, succeeded by a long-term follow-up study (mean 2·2 years, n=17). Second, in 24 patients with idiopathic thrombocytopenic purpura (ITP), IVIG-L was studied for efficacy for 14 days. In both studies, adverse events and vital signs were recorded to study safety. In PID patients treated with IVIG-L, 0·60 and 0·38 severe infections per patient per year were reported during, respectively, the short-term and long-term follow-up. Pharmacokinetic studies resulted in an IgG half-life of 30·9 ± 11·3 days and a mean IgG trough level of 6·8 ± 1·2 g/l. In the ITP study, all patients showed an increase in platelet counts after infusion with IVIG-L, and 20/24 patients responded with a platelet count >50 × 10(9) /l (83·3%) within 1 week. IVIG-L infusions did not cause clinical relevant changes in laboratory parameters or vital signs. In clinical studies, IVIG-L (Nanogam®) demonstrated to be efficacious, well tolerated and safe. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.
Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro
We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [ P =0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P =0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P =0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Full Text Available Abstract Background Expression of inflammatory cytokines in cerebrospinal fluid (CSF has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS. It has been shown that therapy with intravenous immunoglobulin (IVIG improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. Methods From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml, and were assessed for clinical variables by performing the Short Form-36 survey (SF-36 questionnaire assessment, the 6 minute walk distance test (6MWT and registering pain level by Visual Analogue Scale (VAS after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Results Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p Conclusions IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.
Rispens, Theo; Himly, Martin; Ooievaar-de Heer, Pleuni; den Bleker, Tamara H.; Aalberse, Rob C.
To prevent multimer formation, intravenous immunoglobulin (IVIG) is often treated with traces of pepsin. So far, the mechanism behind this treatment has been unclear. Recently, we reported that human IgG4 binds other IgG molecules via Fc-Fc interactions. Here we show that IVIG treated with traces of
Full Text Available Although intravenous immunoglobulin (IVIG is highly effective in Kawasaki disease (KD, mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I, the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG.We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (sST6Gal-I levels were measured by ELISA.There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively.Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.
Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi
A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.
Pranzatelli, Michael R; Tate, Elizabeth D
Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017
Tselmin, Sergey; Julius, Ulrich; Bornstein, Stefan R; Hohenstein, Bernd
Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis. We conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle. A total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5-16], the median IgG reduction was 82 [11-99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy. Immunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable. Copyright © 2017 Elsevier B.V. All rights reserved.
Markvardsen, L H; Debost, J-C; Harbo, T; Sindrup, S H; Andersen, H; Christiansen, I; Otto, M; Olsen, N K; Lassen, L L; Jakobsen, J
We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (-2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40-m-walking test (40-MWT), nine-hole-peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (P < 0.05) as compared with a decline of 14.4 ± 20.3% (P < 0.05) in the placebo group; the difference between the two groups being significant (P < 0.01). ODSS, NIS, MRC, grip strength and 40-MWT improved following SCIG versus saline. SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.
Demirel, Gamze; Akar, Melek; Celik, Istemi Han; Erdeve, Omer; Uras, Nurdan; Oguz, Serife Suna; Dilmen, Ugur
Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.
Olyaeemanesh, Alireza; Rahmani, Mahbobeh; Goudarzi, Reza; Rahimdel, Abulghasem
Intravenous immunoglobulin (IVIG) is an established treatment of immune mediated demyelinating neuropathy including Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Recent trials suggest its efficacy in treating relapsing- remitting multiple sclerosis. IVIG exerts a number of effects, which may be beneficial in treating multiple sclerosis (MS): Reduction of inflammation, inhibition of macrophages, and promotion of remyelination. The aim of this study was to provide an overall assessment of the existing trials of safety and effectiveness of IVIG in relapsing- remitting MS compared to other drugs currently available for the treatment of disease activity in MS. A systematic search strategy was applied to MEDLINE (PubMed and Ovid Medline (1990- Nov 2014)), Cochrane Library 2014, and Trip Database 2014, CRD. The reference lists from the identified trials, MS clinical handbooks and guidelines for the use of IVIG were studied. This article was conducted without language restrictions. Randomized controlled trials of IVIG in MS were selected. Sixteen double-blinded trails were randomly selected. Ten trials were excluded and we performed a meta-analysis on the six trials (537 participants) of IVIG in comparison to placebo. The methodological quality of the trials was assessed using Jadad checklist. The meta-analysis showed a significant beneficial effect on proportion of relapse-free patients (OR: 1.693; 95% CI-1.205-2.380), on the proportion of patients who improved (OR:2.977; 95% CI 1.769-5.010; p=0.0001) and deteriorated (OR:0.522; 95% CI0.330-0.827; p=0.006) between placebo and IVIG-treated patients. In addition, there was a reduction in the annual relapse rate in the IVIG group compared to placebo, which was statistically significant (SMD=-0.218; 95% CI-0.412 to -0.024; p=0.028). The results of the meta-analysis did not show significant differences between Expanded Disability Status Scale (EDSS) changes from baseline (SMD,-0.025; 95% CI,-0
Ye, Qing; Gong, Fang-Qi; Shang, Shi-Qiang; Hu, Jian
Kawasaki disease (KD) has become the most common cause of acquired heart disease in children and is also a risk factor for ischemic heart disease in adults. However, Kawasaki disease lacks specific laboratory diagnostic indices. Thus, this study analyzed the T cell activation profiles of Kawasaki disease and assessed their value in the diagnosis of Kawasaki disease and the prediction of intravenous immunoglobulin (IVIG) sensitivity. We analyzed human leukocyte antigen-DR (HLA-DR), CD69 and CD25 expression on peripheral blood CD4+ and CD8+ T cells during the acute phase of KD. We compared the percentages of HLA-DR+/CD69+/CD25+ T cells in the CD4+ and CD8+ T cell populations of IVIG-effective and IVIG-resistant groups. Receiver operating characteristic curves were used to assess the diagnostic value of the above parameters. The median percentage of CD8+HLA-DR+ T cells and the median ratio of CD8+HLA-DR+ T cells/CD8+CD25+ T cells were significantly elevated in the patient group compared with those in the control group during the acute phase of KD. Regarding the diagnosis of Kawasaki disease, the area under the ROC curve was 0.939 for the percentage of CD8+HLA-DR+ T cells. There was a significant difference in the ratio of CD8+HLA-DR+ T cells/CD8+CD69+ T cells between IVIG-resistant patients and IVIG-sensitive patients. Regarding IVIG sensitivity, the area under the ROC curve was 0.795 for it. Excessive CD8+ T cell activation, as well as an imbalance between CD8+ T cell activation and inhibition, underlies the pathogenesis of Kawasaki disease. The percentage of CD8+ HLA-DR+ T cells may be used as an index to diagnose Kawasaki disease. IVIG inhibits CD8+ T cell activation, but excessive CD8+ T cell activation may cause IVIG resistance. The ratio of CD8+HLA-DR+ T cells/CD8+CD69+ T cells may be used as a predictor of IVIG sensitivity. Copyright © 2016. Published by Elsevier Inc.
Full Text Available With retrospective evaluation of 44 patients suffering from Guilan-Barre Syndrome (GBS, Chronic Idiopathic Demtyelinative Polyradiculoneuropathy (CIDP and Myasthenia Gravis (MG treated with intravenous immunoglobulin, we found following results: 1 Initial symptoms of improvement on forth or fifth days. 2 Maximum recovery for CIDP and MG were after 16-24 and 3-11 days, respectively. 3 No major complication, but mild side effects in 32% of patients. 4 In patients with GBS one grade improvement achieved after 8-30 days. 5 Intravenous immunoglobulin (IVIG plus plasmapheresis had no advantages over IVIG alone. 6 No reasonable conclusion about relapsing rate and duration of response due to follow up restrictions.
Gil-Fernández, Juan José; Flores Ballester, Elena; González Martínez, María; Arévalo-Serrano, Juan; Tamayo Martín, Ana Teresa; Burgaleta Alonso de Ozalla, Carmen
To analyze haemolytic episodes in patients with warm antibody autoimmune haemolytic anemia (AIHA) and compare corticosteroids treatment with intravenous immunoglobulins (IVIG) (group A) or without IVIG (group B). Observational study that includes 21 haemolytic episodes occurred in 17 patients (9 males and 12 females), with a median age of 59 years (26-82). In group A, 8 episodes received IGIV + corticosteroids and in group B, 12 episodes received only corticosteroids and one rituximab. Hemoglobin (Hb) value at diagnosis was 1.8 g/dl lower (95% confidence interval: 0.6 to 3.1; P = .007) in group A, with a median Hb of 6.3g/dl in this group vs 7.9 g/dl in group B. There were non-significant differences in red blood cells transfusion (50 vs 23%; P > .20) and global increase of Hb values (7.3 vs 5.6; P > .20). Overall hematological responses were similar: 88 vs 92% (P > .20). Hematological response achieved in more severe episodes with the use of IVIG was similar to non-severe episodes treated without IVIG. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Bellac, C L; Polatti, D; Hottiger, T; Girard, P; Sänger, M; Gilgen, M
Recent reports of severe haemolytic reactions upon high dose treatment with new generation intravenous immunoglobulins (IVIGs) prompted us to examine the anti-A and anti-B haemagglutinin content of these therapeutics. We compared four different test methods, namely the indirect and direct haemagglutination test as described in the European Pharmacopoiea (Ph. Eur.) and two commercial gelcard systems with the aim to define the most reliable method for a large-scale comparison of different IVIG products. Absolute titres varied when the same samples were analyzed by the four methods, while the relative ranking of six different IVIG preparations representing different manufacturing classes was identical. New generation IVIGs showed 1-2 titre steps higher anti-A titres than the older products. Haemagglutinin titres of all 48 IVIG batches analyzed were within the current Ph. Eur. specification of ≤1:64 when tested by the official pharmacopoeial method. Based on efficiency, reliability and lower costs, the direct gelcard method could be a valid alternative to the official Ph. Eur. method to serve as a limit test. However, due to the highest intermediate precision, the official Ph. Eur. method seems to be most suitable to compare haemagglutinin titres of different IVIG products. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Alsina, Laia; Mohr, Andreas; Montañés, Maria; Oliver, Xènia; Martín, Esperanza; Pons, Jaime; Drewe, Elizabeth; Papke, Jens; Günther, Georg; Chee, Ronnie; Gompels, Mark
Direct comparisons of tolerability and safety of concentrated intravenous immunoglobulin (IVIG) versus less concentrated products are scarce. In this postauthorization, prospective, observational, multicenter study, a systematic comparison of 10% and 5% concentrations of Flebogamma® DIF IVIG was performed in both adult and pediatric patients treated with the studied IVIG products according to the approved indications under routine conditions. Dose of product administered, adverse events (AEs), physical assessments, laboratory tests, and concomitant therapy were analyzed. Patient recruitment in the 10% and 5% product groups was, respectively, 34 (32 analyzed, 13 of them children, receiving 130 IVIG infusions) and 35 (34 analyzed, receiving 135 IVIG infusions). Twenty-four infusions (18.5%; 95% CI: 11.8, 25.1) with the 10% product and 3 (2.2%; 95% CI: -0.3, 4.7) with the 5% product were associated with potentially treatment-related AEs (P DIF 10% and 5% concentrations, which were therefore deemed as safe and well-tolerated IVIG in the studied population. The frequency of infusions associated with treatment-related AEs was lower with the 5% concentration. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.
Full Text Available Alzheimer's disease (AD is the most common neurodegenerative disorder. Currently available therapies are symptomatic but do not alter underlying disease progression. Immunotherapeutic approaches such as anti Aβ peptide active vaccination trials have had limited success to date. Intravenous immunoblobulin (IVIg is widely used in immune-mediated neurological disorders such myasthenia gravis and Guillain-Barre syndrome. These preparations have been obtained from the pooled plasma of healthy human donors and contain natural anti-amyloid antibodies and are well tolerated. A small pilot study of passive immunotherapy using IVIg has suggested cognitive improvement. A multicenter phase III trial is ongoing and will determine whether or not this treatment can ameliorate cognitive deficits in mild-to-moderate AD. Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date. We also summarize what is known about naturally occurring anti-Aβ and tau antibodies in IVIg with a view toward explaining potential mechanisms underlying their therapeutic effects.
Full Text Available Abstract Intravenous immunoglobulin (IVIg is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson’s disease (PD, we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4+/CD8+ ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P P P
Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl
INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may...
Salmun, L M; Barlan, I; Wolf, H M; Eibl, M; Twarog, F J; Geha, R S; Schneider, L C
There is a significant group of patients with severe asthma who require chronic use of systemic steroids for control of their disease. These patients are at risk for severe side effects from oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties, and a few open-label trials have suggested its possible benefit in individuals with severe asthma. This study was designed to assess the potential benefit of IVIG as a steroid-sparing agent in patients with severe asthma. Thirty-eight immunocompetent steroid-requiring patients with severe asthma were randomly enrolled in a double-blind, placebo-controlled trial of IVIG. Of the 38 patients enrolled, 28 patients completed the study. A significant reduction in oral steroid requirement was observed in both the IVIG-treated (n = 16) and the placebo-treated (n = 12) patients. Further exploration of the results showed that IVIG, but not placebo, had a significant steroid-sparing effect in patients requiring high doses of oral steroids (ie, >2000 mg in the year before the study). Within this subgroup, IVIG treatment (n = 9) resulted in a significant decrease in oral steroid requirement, with a median of 16.4 mg/day during the pretreatment period to 3 mg/day during the treatment phase (P =. 0078). No significant decrease in oral steroid requirement was observed in placebo-treated patients (n = 8) within this subgroup. Objective and subjective parameters of the patients' asthma were unchanged in spite of the steroid tapering achieved in the group treated with IVIG. IVIG may be a useful steroid-sparing agent in patients with severe asthma requiring high doses of oral steroids.
Gokturk, Bahar; Pekcan, Sevgi; Guner, Sukru Nail; Artac, Hasibe; Keles, Sevgi; Kirac, Mine; Reisli, Ismail
The appropriate treatment of pandemic H1N1 influenza which was first identified in April 2009 in Mexico is insufficient especially for immunocompromised patients. We aimed to evaluate the features and prognostic factors of the children with H1N1, especially immunocompromised ones, and whether intravenous immunoglobulin G (IVIG) replacement could aid for a better outcome. Twenty-one hospitalized children with laboratory-confirmed H1N1 were evaluated retrospectively. Data were extracted from files and electronic medical records. The median age was 37 (1-216) months; 62% of them were under 5 years of age and 71.4% had one or more underlying disorders. Main symptoms were high fever, cough, fatigue and vomiting. Lower respiratory tract manifestations were seen in 66.6% of children. Mortality rate was 4.7%. The patient who died had the lowest lymphocyte (100/mm(3) ), thrombocyte (21 000/mm(3) ) and highest blood urea nitrogen (87 mg/dL) levels. Fifty-eight percent of evaluated patients had one of the primary immunodeficiency disorders. Surprisingly, none of the six patients with primary immunodeficiency who are on regular IVIG replacement needed intensive care unit and died. Although median durations of cough, fever and hospitalization were lower, they did not change statistically according to get IVIG replacement regularly (P = 0.47, 0.97, 0.09, respectively). Our study is important while it is the first one that shows the course of primary immunodeficient children with H1N1 infection who were on regular IVIG replacement. A trial of high-dose IVIG may be a useful adjunctive therapy in severe H1N1 influenza, particularly in the immunocompromised patients. © 2014 John Wiley & Sons Ltd.
Kim, Han Wool; Lee, Ji Hyen; Cho, Hye Kyung; Lee, Hyunju; Seo, Ho Seong; Lee, Soyoung; Kim, Kyung Hyo
Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0-11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635-5,706 (serotype Ia), 488-1,421 (serotype Ib), and 962-3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups. © 2017 The Korean Academy of Medical Sciences.
Gogou, Maria; Papadopoulou-Alataki, Efimia; Spilioti, Martha; Alataki, Sofia; Evangeliou, Athanasios
While there are guidelines for the use of intravenous immunoglobulins in children with Guillain-Barre syndrome and myasthenia gravis based on high-level evidence studies, data are scarce for the majority of neurologic disorders in this age group. Neuronal antibodies are detected in children with seizures of autoimmune etiology. Intravenous immunoglobulins with their broad immunomodulatory mechanism of action could be ideally effective in different forms of immunedysregulated intractable epilepsies such as autoimmune epilepsy and autoimmune Rasmussen encephalitis. We conducted a systematic review of the literature for evidence of the use of intravenous immunoglobulins in a variety of neurologic diseases in childhood. A comprehensive literature search was conducted using Pubmed as the medical database source without date range. Prospective studies in pediatric groups including objective measures of clinical outcomes were systematically selected. A total of 11 prospective studies were identified in the literature demonstrating a favorable effect of this therapeutic option in children with drug-resistant epilepsy and in cases of encephalitis. No serious adverse effects were reported. No prospective studies about the use of intravenous immunoglobulins in children with demyelinating disorders or neurologic paraneoplasmatic syndromes were found. In this review, we summarize the recent advances in the field of intravenous immunoglobulins used in pediatric neurological diseases. Literature data supports a beneficial effect in this age group. Whilst awaiting the results of large scale studies, administration of intravenous immunoglobulins could be justified in refractory child epilepsy. Otherwise, its use should be guided by the individual needs of each child, depending on the underlying neurological disease. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)
textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional
Gonzalez, Henrik; Khademi, Mohsen; Borg, Kristian; Olsson, Tomas
Expression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-γ and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05). IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for
High dose intravenous immunoglobulin in Rh and ABO hemolytic disease of Egyptian neonates. INTRODUCTION. Hemolytic disease of the newborn (HDN) due to red cell alloimmunisation is an important cause of hyperbilirubinemia with significant morbidity in the neonatal period.1,2. Hemolytic disease of the newborn has ...
Burnouf, Thierry; Sayed, Makram A; Radosevich, Miryana; El-Ekiaby, Magdy
The capacity of hydrophobic octadecyl (C18) and SDR HyperD materials to remove the combination of 1% (v/v) solvent (tri-n-butyl phosphate, TnBP) with 1% (v/v) nonionic detergents (Triton X-100 and Triton X-45) used for viral inactivation of plasma-derived polyvalent intravenous immunoglobulin G (IVIG) preparation has been evaluated. Efficient removal of TnBP (SDR HyperD/7 ml of IVIG. Binding capacities of TnBP were greater than 140 mg/g of C18 and greater than 318 mg/g of dry SDR HyperD. Complete removal of Triton X-45 (SDR HyperD/7 ml of IVIG or above, corresponding to binding capacities in excess of 70 mg/g of C18 and in excess of 159 mg/g of dry SDR HyperD. Residual Triton X-100 was less than 30 ppm at a ratio of 4 g/14 ml of immunoglobulin G (IgG) for the C18 sorbent. Triton X-100 was less than 10 ppm when using SDR HyperD at a ratio of 0.66 g/7 ml of IgG, corresponding to a binding capacity of approximately 106 mg of Triton X-100/g of dry SDR HyperD. Good recoveries of IVIG were achieved in the effluent from both sorbents.
Ballow, Mark; Pinciaro, Paul J; Craig, Timothy; Kleiner, Gary; Moy, James; Ochs, Hans D; Sleasman, John; Smits, William
The previous studies with Flebogamma(®) 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5 % DIF for replacement therapy in children (age 2-16) with primary immunodeficiency diseases (PIDD). IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300-800 mg/kg every 21-28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels. The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations. Flebogamma(®) 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma(®) 5 % for the treatment of children with primary humoral immunodeficiency diseases.
Patro, Rob; Norel, Raquel; Prill, Robert J; Saez-Rodriguez, Julio; Lorenz, Peter; Steinbeck, Felix; Ziems, Bjoern; Luštrek, Mitja; Barbarini, Nicola; Tiengo, Alessandra; Bellazzi, Riccardo; Thiesen, Hans-Jürgen; Stolovitzky, Gustavo; Kingsford, Carl
Understanding the interactions between antibodies and the linear epitopes that they recognize is an important task in the study of immunological diseases. We present a novel computational method for the design of linear epitopes of specified binding affinity to Intravenous Immunoglobulin (IVIg). We show that the method, called Pythia-design can accurately design peptides with both high-binding affinity and low binding affinity to IVIg. To show this, we experimentally constructed and tested the computationally constructed designs. We further show experimentally that these designed peptides are more accurate that those produced by a recent method for the same task. Pythia-design is based on combining random walks with an ensemble of probabilistic support vector machines (SVM) classifiers, and we show that it produces a diverse set of designed peptides, an important property to develop robust sets of candidates for construction. We show that by combining Pythia-design and the method of (PloS ONE 6(8):23616, 2011), we are able to produce an even more accurate collection of designed peptides. Analysis of the experimental validation of Pythia-design peptides indicates that binding of IVIg is favored by epitopes that contain trypthophan and cysteine. Our method, Pythia-design, is able to generate a diverse set of binding and non-binding peptides, and its designs have been experimentally shown to be accurate.
Full Text Available The efficacy of intravenous immunoglobulins (IVIg in patients with autoimmune diseases (AID has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8% were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.
Full Text Available Ritsuko Kubota-Koketsu,1,2 Mikihiro Yunoki,2,3 Yoshinobu Okuno,1 Kazuyoshi Ikuta21Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kagawa; 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3Pathogenic Risk Management, Benesis Corporation, Osaka, JapanAbstract: Influenza A H2N2 virus, also known as the Asian flu, spread worldwide from 1957 to 1967, although there have been no cases reported in humans in the past 40 years. A vaccination program was introduced in Japan in the 1960s. Older Japanese donors could have been naturally infected with the H2N2 virus or vaccinated in the early 1960s. Human intravenous immunoglobulin (IVIG reflects the epidemiological status of the donating population in a given time period. Here, the possible viral neutralizing (VN activities of IVIG against the H2N2 virus were examined. Hemagglutination inhibition (HI and VN activities of IVIG lots manufactured from 1993 to 2010 in Japan and the United States were evaluated against H2N2 viruses. High HI and VN activities against H2N2 viruses were found in all the IVIG lots investigated. HI titers were 32–64 against the isolate in 1957 and 64–128 against the isolates in 1965. VN titers were 80–320 against the isolate in 1957 and 1280–5120 against the isolates in 1965. Both the HI and VN titers were higher against the isolate in 1965 than in 1957. Thus, antibody titers of IVIG against influenza viruses are well correlated with the history of infection and the vaccine program in Japan. Therefore, evaluation of antibody titers provides valuable information about IVIGs, which could be used for immune stimulation when a new influenza virus emerges in the human population.Keywords: IVIG, influenza, H2N2, neutralization
Ye, Liang-ping; Zhang, Cheng; Zhu, Qi-xing
Background Intravenous immunoglobulin (IVIG) treatment is commonly used to treat Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with controversial therapeutic effect. Methods We conducted a comprehensive meta-analysis through combining the published eligible studies to evaluate the effectiveness of IVIG on SJS and TEN treatment. Results A total of 26 studies were selected from public available databases. The combination of IVIG and corticosteroid markedly reduced the recovery time (by 1.63 days, 95% CI: 0.83–2.43, P < 0.001), compared with solo corticosteroid group. The favorable effects were greater in Asian (2.19, 95% CI: 1.41–2.97, P < 0.001), TEN (2.56, 95% CI: 0.35–4.77, P = 0.023) and high-dose IVIG treated individuals (1.78, 95% CI: 0.42–3.14, P = 0.010). The hospitalization length reduced by 3.19 days (95% CI: 0.08–6.30, P = 0.045), though the outcome was proven to be unstable. We found heterogeneities, which sources were probably regional factors. Besides, IVIG was inclined to decrease SJS/TEN mortality (SMR: 0.84, 95% CI: 0.66–1.08, P = 0.178). This impact was possibly more profound when patients were treated with high dose IVIG (SMR: 0.74, 95% CI: 0.50–1.08, P = 0.116), or when patients were diagnosed as TEN (SMR: 0.68, 95% CI: 0.45–1.01, P = 0.058). Conclusions Our current meta-analysis suggests that IVIG combined with corticosteroid could reduce recovery time for SJS and TEN. This effect is greater among Asian patients. Whereas, its impact on reducing mortality is not significant. PMID:27902746
Full Text Available Intravenous immunoglobulin (IVIG treatment is commonly used to treat Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN with controversial therapeutic effect.We conducted a comprehensive meta-analysis through combining the published eligible studies to evaluate the effectiveness of IVIG on SJS and TEN treatment.A total of 26 studies were selected from public available databases. The combination of IVIG and corticosteroid markedly reduced the recovery time (by 1.63 days, 95% CI: 0.83-2.43, P < 0.001, compared with solo corticosteroid group. The favorable effects were greater in Asian (2.19, 95% CI: 1.41-2.97, P < 0.001, TEN (2.56, 95% CI: 0.35-4.77, P = 0.023 and high-dose IVIG treated individuals (1.78, 95% CI: 0.42-3.14, P = 0.010. The hospitalization length reduced by 3.19 days (95% CI: 0.08-6.30, P = 0.045, though the outcome was proven to be unstable. We found heterogeneities, which sources were probably regional factors. Besides, IVIG was inclined to decrease SJS/TEN mortality (SMR: 0.84, 95% CI: 0.66-1.08, P = 0.178. This impact was possibly more profound when patients were treated with high dose IVIG (SMR: 0.74, 95% CI: 0.50-1.08, P = 0.116, or when patients were diagnosed as TEN (SMR: 0.68, 95% CI: 0.45-1.01, P = 0.058.Our current meta-analysis suggests that IVIG combined with corticosteroid could reduce recovery time for SJS and TEN. This effect is greater among Asian patients. Whereas, its impact on reducing mortality is not significant.
Masuzawa, Yuko; Mori, Masaaki; Hara, Takuma; Inaba, Aya; Oba, Mari S; Yokota, Shumpei
Although there are many reports on the resistance of Kawasaki disease (KD) to initial intravenous immunoglobulin (IVIg) therapy, risk factors for coronary artery lesions in such cases remain to be established. The objective of this study was to explore when additional therapies should be administered and to identify factors helpful for selecting a therapeutic option. Based on their written clinical records, we performed a retrospective review of KD patients who did not respond to initial IVIg therapy and who therefore then underwent plasma exchange (PE) therapy. This was a case-control study to compare the presence or absence of acute coronary lesions in patients treated by PE for IVIg-unresponsive KD at Yokohama City University Hospital or at Yokohama City University Medical Center. Fifteen of 44 patients had acute coronary artery lesions (CAL) correlating with high levels of white blood cells (WBC) (P = 0.045), D-dimer (P = 0.008), and fibrin/fibrinogen degradation products (P = 0.009) and lower levels of fibrinogen (P = 0.013) prior to PE therapy. There was a strong correlation between pre-PE levels of albumin and D-dimer (Pearson's correlation coefficient of 0.610). Multivariate analyses revealed that the odds ratio for CAL when D-dimer was ≥ 4.5 μg/mL was 25.06 (95% CI, 2.56-244.91, P = 0.006). D-dimer elevation and albumin decline in IVIg-unresponsive KD patients could be risk factors for acute CAL, suggesting the possibility that angitis has spread throughout the arterial system, as far as the coronary artery. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.
Bellone, Michael; Boctor, Fouad N
Maternal D alloimmunization detected in early gestation requires aggressive intervention to prevent severe fetal anemia. An intrauterine transfusion (IUT) is indicated to prevent fetal death once severe fetal anemia has been detected, but is not without risk. Protocols combining therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG) have been described, but they usually bridge to IUT. We describe a 27-year-old G4, P0-1-2-0 Caucasian female with a history of ruptured ectopic pregnancy presented at 12 weeks' gestation with a very high anti-D titer (2048). TPE was performed on that week and twice more in the following week, with a fourth final exchange during Week 14. A loading dose of IVIG (2 g/kg) was administered over 2 days after the third TPE and then 1 g/kg per week until Week 28 (total, 14 doses). The antibody titer decreased to 256 by the beginning of 15 weeks' gestation and remained stable at that level for the remainder of the pregnancy. Doppler ultrasonographic measurements of the fetal middle cerebral artery peak flow velocity performed throughout gestation showed no evidence of fetal anemia. A healthy male infant was delivered at 37 weeks' gestation with mild immune-mediated hemolysis. The infant underwent successful treatment with an IVIG dose of 750 mg/kg and a red blood cell exchange. Our unique TPE-IVIG protocol was successful at preventing the onset of severe fetal anemia in a patient with high titer anti-D. Since IUT may be fatal, our approach offers a safer and less-invasive treatment regime that can adequately sustain a fetus until term. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD
Anzai, Tatsuya; Minami, Takaomi; Sato, Tomoyuki; Furui, Sadahiro; Yamagata, Takanori
Intravenous immunoglobulin therapy is standard for Kawasaki disease (KD) treatment; however, anaphylactic reactions to immunoglobulins are a risk in KD patients with selective IgA deficiency (sIgAD). The therapy for KD associated with sIgAD has not been established. The IgA immune response is believed to play an important role in KD vasculitis. We report the case of a 5-year-old boy with KD and sIgAD treated with intravenous cyclosporine A (CsA, 3.0 mg/kg/day) instead of intravenous immunoglobulin (IVIG). The fever and inflammation immediately resolved without a coronary artery lesion. In KD patients with sIgAD, we believe that an IgA immune response is lacking, which is the reason for milder KD symptoms than in those without sIgAD. This case report aids in clarifying the role of IgA antibodies in KD and provides evidence that CsA is a potential candidate for first-line therapy for patients with KD with contraindications to IVIG.
IVIG consumption is increasing due to the fact that in many cases the drugs are being used off-label. IVIG were more likely to be used in autoimmune and systemic inflammatory diseases. However, in randomized clinical trials, a good effect was achieved only in Kawasaki disease and immune thrombocytopenic purpura. Current clinical guidelines narrowed the indications for IVIG, limiting their use in sepsis. Immunoglobulin replacement therapy is recommended for children with physiological delay of immunoglobulin production only in repeated infections, which can not be controlled or prevented with antibiotics. In secondary ID, replacement therapy must be carried out if the cause of hypogammaglobulinemia can not be eliminated or elimination is contraindicated, as well as in association with β-cell cancers, in which severe infections caused by encapsulated bacteria persist despite preventive antibiotic therapy.
Diep, Binh An; Le, Vien T M; Badiou, Cedric; Le, Hoan N; Pinheiro, Marcos Gabriel; Duong, Au H; Wang, Xing; Dip, Etyene Castro; Aguiar-Alves, Fábio; Basuino, Li; Marbach, Helene; Mai, Thuy T; Sarda, Marie N; Kajikawa, Osamu; Matute-Bello, Gustavo; Tkaczyk, Christine; Rasigade, Jean-Philippe; Sellman, Bret R; Chambers, Henry F; Lina, Gerard
New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus. Copyright © 2016, American Association for the Advancement of Science.
The development of effective, safe, liquid intravenous immunoglobulins (IVIG) preparations has represented a major therapeutic advancement in the treatment of patients with antibody deficiencies. Flebogamma 5% was the first liquid IVIG licensed in Europe that has been widely used in the treatment of immunodeficiency diseases. It has been proven to have an excellent efficacy and safety profile. Flebogamma 5% dual inactivation and filtration (DIF) is a newly developed IVIG preparation that shares formulation characteristics and identical biochemical and stability profiles with Flebogamma 5%. In addition to pasteurization, already performed in Flebogamma 5%, solvent-detergent treatment and sequential nanofiltration through filters with pore sizes of 35 nm followed by 20 nm have been added to further enhance the pathogen safety margin. The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma 5% DIF for immunoglobulin replacement therapy in patients with primary immunodeficiency diseases (PID). Flebogamma 5% DIF was administered at seven clinical sites to 46 subjects with well-defined primary immunodeficiency diseases at a dose of 300-600 mg/kg every 21-28 days for 12 months. The serious bacterial infection rate was 0.021/subject/year. The incidence of adverse events considered potentially related to Flebogamma 5% DIF during or within 72 h after completing an infusion was approximately 10%. The half-life in serum of the administered IgG was around 31 days. In summary, Flebogamma 5% DIF is efficacious and safe, has good pharmacokinetic properties, is well-tolerated and maintains the profile of Flebogamma 5% for the treatment of patients with primary humoral immune deficiency diseases.
Buchacher, Andrea; Krause, Dagmar; Wiry, Gerda; Weinberger, Josef
Endotoxins have been measured routinely in the final product and during the production process to produce non-pyrogenic parenterals. Limulus-amoebocyte-lysate-reactive material was found in in-process samples and final product of one of Octapharma's intravenous immunoglobulin (IVIG) preparations. Limulus-amoebocyte-lysate (LAL) is activated by bacterial endotoxins and by (1→3)-β-D-glucans. The contribution of both compounds on the LAL-related signal was determined by three different approaches: (1) using a test specific for (1→3)-β-D-glucans, (2) by addition of β-glucan blocker, and (3) by the use of a recombinant endotoxin assay. It was shown that none of our IVIG concentrates contained elevated endotoxin contents but that the higher LAL reaction could be ascribed to (1→3)-β-D-glucans extracted from cellulose filter pads. The use of an endotoxin test kit highly sensitive for (1→3)-β-D-glucans might lead to false-positive results. (1→3)-β-D-glucans spike solutions did not evoke an increase of temperature in rabbits, suggesting that a pyrogenic reaction is not expected in patients. Endotoxins have been measured routinely in the final product and during the production process to produce non-pyrogenic parenterals. Limulus-amoebocyte-lysate-reactive material was found in in-process samples and final product of one of Octapharma's intravenous immunoglobulin (IVIG) preparations. Limulus-amoebocyte-lysate (LAL) is activated by bacterial endotoxins and by (1→3)-β-D-glucans. The contribution of both compounds on the LAL-related signal was determined by three different approaches: (1) using a test specific for (1→3)-β-D-glucans, (2) by addition of β-glucan blocker, and (3) by the use of a recombinant endotoxin assay. It has been shown that none of our IVIG concentrates contained elevated endotoxin contents but that the higher LAL reaction could be ascribed to (1→3)-β-D-glucans extracted from cellulose filter pads. The use of an endotoxin test kit
Esen, Figen; Senturk, Evren; Ozcan, Perihan E; Ahishali, Bulent; Arican, Nadir; Orhan, Nurcan; Ekizoglu, Oguzhan; Kucuk, Mutlu; Kaya, Mehmet
The effects of immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M on blood-brain barrier integrity and survival rates in septic rats were comparatively investigated. Sepsis was induced by cecal ligation and perforation in Sprague-Dawley rats. The animals were divided into the following groups: Sham, cecal ligation and perforation, cecal ligation and perforation plus immunoglobulin G (250 mg/kg, intravenous), and cecal ligation and perforation plus immunoglobulins enriched with immunoglobulin A and immunoglobulin M (250 mg/kg, intravenous). Immunoglobulins were administered 5 mins before cecal ligation and perforation and the animals were observed for behavioral changes for 24 hrs following cecal ligation and perforation. Blood-brain barrier permeability was functionally and structurally evaluated by determining the extravasation of Evans Blue and horseradish peroxidase tracers, respectively. Immunohistochemistry and Western blotting for occludin were performed. The high mortality rate (34%) noted in the septic rats was decreased to 15% and 3% by immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M, respectively (p immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M alleviated the symptoms of sickness behavior in the septic rats, with the animals becoming healthy and active. Increased extravasation of Evans Blue into the brain tissue of the septic rats was markedly decreased with the administration of both immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M (p immunoglobulin G or immunoglobulins enriched with immunoglobulin A and immunoglobulin M treatment, no ultrastructural evidence of leaky capillaries in the brain was observed in the septic rats, indicating the blockade of the transcellular pathway by immunoglobulins administration. Our study suggests that immunoglobulin G and immunoglobulins enriched with
Alexandre Paulo Machado de Brito
Full Text Available Introduction: Direct costs for treating Guillain-Barré Syndrome (GBS represent a significant financial burden to public hospitals. Few studies compared the cost of plasma exchange (PE treatment with human intravenous immunoglobulin (IVIg. Objectives: To compare the cost of two therapies for GBS: IVIg and PE. Secondary objective was to evaluate compliance to IVIg prescription guidelines of the Pharmacy and Therapeutics Committee (PTC. Methods: A cross-sectional study included 25 patients with GBS admitted in a university affiliated hospital from June, 2003 through June, 2008. The costs of IVIg (n=20 and PE (n=5 were evaluated through the cost minimization method, considering direct medical costs yield by the management of the institution. Patients receiving treatments other than PE or IVIg were excluded. Data were collected by medical records review. Clinical endpoint was disability on discharge, established by the 7-point scale of Hughes. Compliance to the PTC guidelines was evaluated considering the dose and prescription regime of IVIg. Results: Twenty-five participants, ranging from 2 to 70 years of age, were included. No difference occurred in any medical variables related to the treatment or in the main clinical outcome measured by the Hughes’ scale. The mean direct cost of PE treatment was US$ 6,059± 1,701 per patient, and the same expense for IVIg was US$ 18,344±12,259 (P = 0.035. Total inpatient cost was US$ 25,730± 18,714 in the PE group, and 34,768± 27,766 (p=0.530 in the IVIg group. Conclusions: In a university-based hospital, PE is equally effective and less expensive than IVIg to treat GBS.
Ahmadi, Majid; Abdolmohammadi-Vahid, Samaneh; Ghaebi, Mahnaz; Aghebati-Maleki, Leili; Afkham, Amir; Danaii, Shahla; Abdollahi-Fard, Sedigheh; Heidari, Lida; Jadidi-Niaragh, Farhad; Younesi, Vahid; Nouri, Mohammad; Yousefi, Mehdi
Women with elevated natural killer (NK) cell frequency and function during pregnancy, suffer from recurrent pregnancy loss (RPL). In the present study, the possible effect of intravenous immunoglobulin (IVIG) administration on Th1 and Th2 cell frequency, cytokine secretion, and expression of transcription factors is compared between RPL patients and control group. Totally, 44 women with a history of RPL (32 women as treated group and 12 as control group) were enrolled in the study. The frequency of Th1 and Th2 lymphocytes, the expression of transcription factors related to these cells and the serum levels of associated cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. All, assessments were performed both before and after treatment with IVIG. A significant reduction in Th1 lymphocyte frequency, transcription factor expression and cytokine levels were observed in IVIG-treated group, while all the above parameters indicated a significant increase for Th2 lymphocytes. Th1/Th2 ratio decreased significantly (p value<0.0001) at the end of treatment and 28 out of 32 (87.5%) women in IVIG-treated group had live birth in comparison with 5 out of 12 (41.6%) in untreated group. IVIG administration proves to be an efficient therapeutic strategy which is able to enhance the success rate of pregnancy through a shift in Th2 responses. Furthermore, IVIG presents efficacy for the treatment of reproduction failures especially in subjects with immune cell abnormalities and increased NK cell level and function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Serial Serum Immunoglobulin G (IgG) Trough Levels in Patients with X-linked Agammaglobulinemia on Replacement Therapy with Intravenous Immunoglobulin: Its Correlation with Infections in Indian Children.
Suri, Deepti; Bhattad, Sagar; Sharma, Avinash; Gupta, Anju; Rawat, Amit; Sehgal, Shobha; Singh, Surjit; Gupta, Sudhir
Patients with primary antibody deficiency (PAD) are being increasingly diagnosed in the developing world. However, care of these children continues to remain suboptimal due to financial and social constraints. Immunoglobulin (Ig) trough level is an important predicting factor for infections in children on replacement immunoglobulin therapy. There are no data on this aspect from the developing world. Therefore, we studied serial immunoglobulin G (IgG) trough levels in 14 children with X-linked agammaglobulinemia (XLA) receiving replacement intravenous immunoglobulin (IVIG). Infections during the course of enrolment were documented prospectively. Mean age at the time of diagnosis was 5.1 years (range 2-11 years). Mean time from onset of symptoms and initiation of therapy was 3.3 years. Two children had established chronic lung disease prior to enrolment. Total numbers of major and minor infections were 7 and 40, respectively. At a mean dose of 414 mg/kg/month of IVIG, mean trough IgG level was 435 mg/dl. Median IgG trough levels during the episodes of major and minor infections were 244 and 335 mg/dl, respectively. An escalation in IVIG dose of 100 mg/kg produced an increase in serum IgG levels by 53.6 mg/dl. Median trough IgG level of 354 mg/dl was found to be protective with 64% sensitivity and 75% specificity. A median dose of 397 mg/kg was required to keep children free of infections. Despite financial constraints and several challenges in the context of a developing country, children with XLA have good outcome on replacement immunoglobulin therapy. Furthermore, mean biological trough IgG levels are much lower than reported in for Western patients; however, studies involving larger number of subjects are required in future to draw firm conclusions.
Kofler, H; Wambacher-Gasser, B; Topar, G; Weinlich, G; Schuler, G; Hintner, H; Romani, N; Fritsch, P
Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the skin and mucous membranes. It is chronic, disabling, and difficult to treat. We describe a case of severe epidermolysis bullosa acquisita of 7 years' duration that had been treated with azathioprine, corticosteroids, chlorambucil, plasma exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting effect. Seven cycles of treatment were administered with immunoglobulin given intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient was free of disease for 10 months after the initiation of therapy. We suggest that low-dose regimens of immunoglobulins may be as effective in this disease as the high-dose regimens suggested in the literature, and at much lower cost.
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.
Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick
Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.
Zhang, Li; Song, Qi-Fang; Jin, Jing-Jie; Huang, Ping; Wang, Zhou-Ping; Xie, Xiao-Fei; Gu, Xiao-Qiong; Gao, Xue-Juan; Jia, Hong-Ling
Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.
van Schaik, I. N.; Lundkvist, I.; Vermeulen, M.; Brand, A.
Intravenous immunoglobulin is used to an increasing extent in various immune-mediated diseases, but its mechanism(s) of action in vivo is incompletely understood. Previous studies have shown that intravenous immunoglobulin may interfere with autoantibodies and their production by B cells and also
Jiang, Wendy; Du, Eileen; Dodel, Richard; Farlow, Martin R.; Zheng, Wei; Du, Yansheng
We have shown that intravenous immunoglobulin (IVIG) contains anti-Aβ autoantibodies and IVIG could induce beta amyloid (Aβ) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Aβ efflux remains unclear. In this study, we used amyloid precursor protein (AβPP) transgenic mice to investigate if the IVIG could induce efflux of Aβ from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Aβ transporter in blood-cerebrospinal fluid barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain Aβ levels by pulling Aβ into the blood system in AβPP transgenic mice. In the mechanistic study, IVIG could induce Aβ efflux through the in-vitro BCB membrane formed by cultured BCB epithelial cells. Both RAP (receptor-associated protein; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Aβ efflux. Should Aβ prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for Alzheimer's disease (AD) by inducing efflux of Aβ from the brain through the LRP1 in the BCB. PMID:24747018
Fazekas, F.; Lublin, F.D.; Li, D.
OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We...... therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety. METHODS: One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo...
Ravindranath, Mepur H; Zhu, Dong; Pham, Tho; Jucaud, Vadim; Hopfield, Judy; Kawakita, Satoru; Terasaki, Paul I
Healthy individuals have natural antibodies (Abs) reacting to allo-human leukocyte antigen (HLA)-la. This could be due to the presence of anti-HLA-E immunoglobulin G (IgG), which was revealed to recognize the peptides shared between HLA-E and HLA-la after peptide inhibition assay. Sera or plasma of multiple donors are pooled to prepare intravenous immune globulin (IVIg). The HLA-la-reactivity of IVIg is abolished when the anti-HLA-E Abs are depleted from the IVIg, suggesting that IVIg contains anti-HLA-E Abs with HLA-la reactivity. Anti-HLA-E monoclonal antibodies (mAbs; e.g., TFL-006 and TFL-007) generated at Terasaki Foundation Laboratory (TFL) differ from commercial HLA-E mAbs in mimicking HLA-la &-lb reactivities of IVIg, which is known to suppress the allo-HLA antibody (Ab) production and the activated CD4+ T cells. Whether HLA-E-mAbs also have the ability to suppress the production of these Abs and activation of T cells like IVIg is evaluated. Indeed, the TFL-mAbs significantly suppressed the allo-HLA-ll Ab production by B cells obtained from a woman alloimmunized postpartum >20 years ago. Similarly, the TFL-mAbs suppressed HLA-I Ab produced by a B-cell hybridoma. In both instances, the suppression was far superior to that by IVIg. Activated T cells were suppressed by both IVIg and the TFL-mAbs dosimetrically. Furthermore, the required concentrations of TFL-mAbs are 150-fold lower than the concentrations of IVIg required for the suppression.
Soares, Marta O; Welton, Nicky J; Harrison, David A; Peura, Piia; Shankar-Hari, Manu; Harvey, Sheila E; Madan, Jason; Ades, Anthony E; Rowan, Kathryn M; Palmer, Stephen J
Prior to investing in a large, multicentre randomised controlled trial (RCT), the National Institute for Health Research in the UK called for an evaluation of the feasibility and value for money of undertaking a trial on intravenous immunoglobulin (IVIG) as an adjuvant therapy for severe sepsis/septic shock. In response to this call, this study assessed the clinical and cost-effectiveness of IVIG (using a decision model), and evaluated the value of conducting an RCT (using expected value of information (EVI) analysis). The evidence informing such assessments was obtained through a series of systematic reviews and meta-analyses. Further primary data analyses were also undertaken using the Intensive Care National Audit & Research Centre Case Mix Programme Database, and a Scottish Intensive Care Society research study. We found a large degree of statistical heterogeneity in the clinical evidence on treatment effect, and the source of such heterogeneity was unclear. The incremental cost-effectiveness ratio of IVIG is within the borderline region of estimates considered to represent value for money, but results appear highly sensitive to the choice of model used for clinical effectiveness. This was also the case with EVI estimates, with maximum payoffs from conducting a further clinical trial between £ 137 and £ 1,011 million. Our analyses suggest that there is a need for a further RCT. Results on the value of conducting such research, however, were sensitive to the clinical effectiveness model used, reflecting the high level of heterogeneity in the evidence base.
Christiansen, Ole B; Nielsen, Henriette Svarre
to patient characteristics and treatment procedures were carried out. One trial found that IvIg significantly improved pregnancy outcome in all patients whereas the remaining trials could either detect no treatment effect at all or only an effect in subsets of patients. In a meta-analysis, the pooled odds...... in this subset compared with placebo. In most trials the design was suboptimal with regard to detecting any treatment effect of IvIg in RM due to low doses or starting the treatment late. A new large placebo-controlled trial should be conducted in RM patients with secondary RM or repeated second trimester fetal...
Betschel, Stephen D.; Warrington, Richard J.; Schellenberg, Robert
In Canada, intravenous immune globulin (IVIg) products are licensed for six disease indications, however it has been demonstrated that patients with a number of other conditions also benefit from IVIg. Here we report the routine clinical use of Octagam? 10?% across three Canadian institutions. A total of 135 patients were treated with Octagam?, for conditions represented by five distinct indication groups. The results of this review indicate that Octagam? has been well adopted and is prescrib...
Full Text Available Catalytic antibodies are immunoglobulins endowed with enzymatic activity. Catalytic IgG has been reported in several human autoimmune and inflammatory diseases. In particular, low levels of catalytic IgG have been proposed as a prognostic marker for chronic allograft rejection in patients undergoing kidney transplant. Kidney allograft is a treatment of choice for patients with end-stage renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is used in patients with donor-specific antibodies, alone or in conjunction with other immunosuppressive treatments, to desensitize the patients and prevent the development of acute graft rejection. Here, we followed for a period of 24 months the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg-methylcoumarinimide in a large cohort of patients undergoing kidney transplantation. Twenty-four percent of the patients received IVIg at the time of transplantation. Our results demonstrate a marked reduction in levels of catalytic antibodies in all patients three months following kidney transplant. The decrease was significantly pronounced in patients receiving adjunct IVIg therapy. The results suggests that prevention of acute graft rejection using intravenous immunoglobulins induces a transient reduction in the levels of catalytic IgG, thus potentially jeopardizing the use of levels of catalytic antibodies as a prognosis marker for chronic allograft nephropathy.
Mahendra, Ankit; Peyron, Ivan; Dollinger, Cécile; Gilardin, Laurent; Sharma, Meenu; Wootla, Bharath; Padiolleau-Lefevre, Séverine; Friboulet, Alain; Boquet, Didier; Legendre, Christophe; Kaveri, Srinivas V.
Catalytic antibodies are immunoglobulins endowed with enzymatic activity. Catalytic IgG has been reported in several human autoimmune and inflammatory diseases. In particular, low levels of catalytic IgG have been proposed as a prognostic marker for chronic allograft rejection in patients undergoing kidney transplant. Kidney allograft is a treatment of choice for patients with end-stage renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is used in patients with donor-specific antibodies, alone or in conjunction with other immunosuppressive treatments, to desensitize the patients and prevent the development of acute graft rejection. Here, we followed for a period of 24 months the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg-methylcoumarinimide in a large cohort of patients undergoing kidney transplantation. Twenty-four percent of the patients received IVIg at the time of transplantation. Our results demonstrate a marked reduction in levels of catalytic antibodies in all patients three months following kidney transplant. The decrease was significantly pronounced in patients receiving adjunct IVIg therapy. The results suggests that prevention of acute graft rejection using intravenous immunoglobulins induces a transient reduction in the levels of catalytic IgG, thus potentially jeopardizing the use of levels of catalytic antibodies as a prognosis marker for chronic allograft nephropathy. PMID:23967092
Intravenous immunoglobulin (IVIG) is a biological agent composed of polyclonal antibodies prepared from a large cohort of human plasma pools. IVIG is increasingly used for the treatment of various antibody-mediated diseases, including pemphigus vulgaris (PV). The aim of the study was to evaluate the benefit and safety profiles of high dose IVIG therapy in PV patients determined by clinical remission, corticosteroid-sparing and immunomodulatory effects, and adverse events at 12 months' follow up. Ten PV patients underwent 3-8 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. The pemphigus disease area index (PDAI) score, direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and corticosteroid dosage were evaluated before IVIG therapy, after each cycle, and at 6 and 12 months' follow up. The baseline PDAI score was 75.70 ± 21.0 and baseline prednisone dosage was 201.60 ± 71.7 mg/day. The PDAI score reduction of 98% was achieved at 12 months' follow up and a corticosteroid dose reduction of 90% corresponded to clinical improvement. The decrease in both values was statistically significant (P = 0.002, respectively). At 12 months' follow up, seven patients were shown to be negative on IIF, of whom three proved to be negative on DIF. Adverse events were mild and transient and did not require the cessation of IVIG therapy. IVIG induced long-term clinical remission, while displaying a corticocorticosteroid-sparing effect and evoking a long-standing immunomodulatory effect in PV patients. The safety profile of IVIG therapy was assessed as good. © 2015 The Australasian College of Dermatologists.
Full Text Available BackgroundAcute hemorrhagic encephalomyelitis (AHEM is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome.ObjectiveTo report the association with Ran Binding Protein (RANBP2 gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP in life-threatening AHEM.DesignSingle case study.Case reportA 6-year-old girl known to have sickle cell disease (SCD presented an acquired demyelinating syndrome (ADS with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day. Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG. She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells.ConclusionIn any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom
Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.
Filomena Monica Cavaliere
Full Text Available The lack of BTK in X-linked agammaglobulinemia (XLA patients does not affect monocytes and polymorphonuclear cells (PMN phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS following engagement of FC gamma receptors (FcγR. XLA monocytes and PMN showed an efficient calcium (Ca2+-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.
Cavaliere, Filomena Monica; Prezzo, Alessandro; Bilotta, Caterina; Iacobini, Metello; Quinti, Isabella
The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.
Mar, Nataliya; Kosowicz, Rebecca; Hook, Karen
We report a case of a 36-year old patient with prior history of thrombosis in a setting of antiphospholipid antibody syndrome (APS) as well as pregnancy-associated catastrophic antiphospholipid syndrome (CAPS), resulting in multi-organ infarction and pregnancy loss. The episode of CAPS occurred while she was receiving antepartum low-dose aspirin and therapeutic-dose enoxaparin. This patient presented again at 6 weeks gestation and ultrasounds were consistent with fetal growth restriction, concerning for placental insufficiency and thrombosis. This time, hydroxychloroquine and monthly intravenous immunoglobulin (IVIG) infusions were added to her prophylaxis regimen, resulting in a successful delivery. Platelet count and antiphospholipid antibody titers were routinely monitored throughout pregnancy as markers of disease activity for APS. Current thromboprophylaxis guidelines do not address therapeutic options to prevent further pregnancy morbidity in women who develop recurrent episodes of thrombosis or CAPS despite receiving adequate anti-thrombotic treatment. Use of hydroxychloroquine and IVIG has been associated with good outcomes in this subset of patients.
Absoud, Michael; Brex, Peter; Ciccarelli, Olga; Diribe, Onyinye; Giovannoni, Gavin; Hellier, Jennifer; Howe, Rosemary; Holland, Rachel; Kelly, Joanna; McCrone, Paul; Murphy, Caroline; Palace, Jackie; Pickles, Andrew; Pike, Michael; Robertson, Neil; Jacob, Anu; Lim, Ming
Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Primary outcome measure - American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures - ASIA motor and sensory scales, Expanded Disability Status Scale
Full Text Available Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous adverse drug reactions. Intravenous immunoglobulin is described as a therapeutic option, however its use is still controversial. Using Epistemonikos database, which is maintained by screening over 20 databases, we identified six systematic reviews, including 39 primary studies. We combined the evidence using tables for summary of findings, following the GRADE approach, and concluded there is uncertainty about the effects of intravenous immunoglobulin because the certainty of the evidence is very low; it probably leads to important adverse effects; and has high cost. Intravenous immunoglobulin should not be used outside the context of a clinical trial, or only in cases where other treatments have failed and there are no resource constraints.
Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero
Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.
Dhawan, Priya S; Goodman, Brent P; Harper, Charles M; Bosch, Peter E; Hoffman-Snyder, Charlene R; Wellik, Kay E; Wingerchuk, Dean M; Demaerschalk, Bart M
Immune therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are first line in the treatment of worsening myasthenia gravis. Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in exacerbations due to cost and ease of administration. To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis. A structured critical appraisal was conducted on the objective topic. This included a creation of a structured question based on a clinical scenario, comprehensive literature search, selection of evidence for review, and critical appraisal of selected evidence. Evidence was summarized and commentary provided. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology. A single-blinded, randomized-controlled trial that compared IVIG and PLEX in 84 patients with worsening myasthenia gravis was selected for review. Primary outcome measure was functional status at 14 days after treatment, as assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically significant differences between IVIG and PLEX groups. IVIG and PLEX are equally effective in worsening myasthenia gravis. Treatment decisions may depend on several variables, including presence of respiratory distress, medical comorbidities, access to medication, and cost. PLEX will likely remain the treatment of choice in true myasthenic crisis.
Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.
Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients wit...
Luštrek, Mitja; Lorenz, Peter; Kreutzer, Michael; Qian, Zilliang; Steinbeck, Felix; Wu, Di; Born, Nadine; Ziems, Bjoern; Hecker, Michael; Blank, Miri; Shoenfeld, Yehuda; Cao, Zhiwei; Glocker, Michael O.; Li, Yixue; Fuellen, Georg; Thiesen, Hans-Jürgen
Epitope-antibody-reactivities (EAR) of intravenous immunoglobulins (IVIGs) determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning with an ensemble of classifiers in combination with position weight matrix (PWM) analysis. Machine learning slightly outperformed PWM with area under the curve (AUC) of 0.884 vs. 0.849. Two different types of epitope-antibody recognition-modes (Type I EAR and Type II EAR) were found. Peptides of Type I EAR are high in tyrosine, tryptophan and phenylalanine, and low in asparagine, glutamine and glutamic acid residues, whereas for peptides of Type II EAR it is the other way around. Representative crystal structures present in the Protein Data Bank (PDB) of Type I EAR are PDB 1TZI and PDB 2DD8, while PDB 2FD6 and 2J4W are typical for Type II EAR. Type I EAR peptides share predicted propensities for being presented by MHC class I and class II complexes. The latter interaction possibly favors T cell-dependent antibody responses including IgG class switching. Peptides of Type II EAR are predicted not to be preferentially presented by MHC complexes, thus implying the involvement of T cell-independent IgG class switch mechanisms. The high extent of IgG immunoglobulin reactivity with human peptides implies that circulating IgG molecules are prone to bind to human protein/peptide structures under non-pathological, non-inflammatory conditions. A webserver for predicting EAR of peptide sequences is available at www.sysmed-immun.eu/EAR. PMID:24244326
Full Text Available Epitope-antibody-reactivities (EAR of intravenous immunoglobulins (IVIGs determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning with an ensemble of classifiers in combination with position weight matrix (PWM analysis. Machine learning slightly outperformed PWM with area under the curve (AUC of 0.884 vs. 0.849. Two different types of epitope-antibody recognition-modes (Type I EAR and Type II EAR were found. Peptides of Type I EAR are high in tyrosine, tryptophan and phenylalanine, and low in asparagine, glutamine and glutamic acid residues, whereas for peptides of Type II EAR it is the other way around. Representative crystal structures present in the Protein Data Bank (PDB of Type I EAR are PDB 1TZI and PDB 2DD8, while PDB 2FD6 and 2J4W are typical for Type II EAR. Type I EAR peptides share predicted propensities for being presented by MHC class I and class II complexes. The latter interaction possibly favors T cell-dependent antibody responses including IgG class switching. Peptides of Type II EAR are predicted not to be preferentially presented by MHC complexes, thus implying the involvement of T cell-independent IgG class switch mechanisms. The high extent of IgG immunoglobulin reactivity with human peptides implies that circulating IgG molecules are prone to bind to human protein/peptide structures under non-pathological, non-inflammatory conditions. A webserver for predicting EAR of peptide sequences is available at www.sysmed-immun.eu/EAR.
Souza, Paulo Victor Sgobbi de; Pinto, Wladimir Bocca Vieira de Rezende; Oliveira, Acary Souza Bulle
During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg). IVIg has been tried in a variety of immune-mediated neurological diseas...
Navarro-Triviño, F J; Pérez-López, I; Ruíz-Villaverde, R
Intravenous immunoglobulin (IVIG) replacement therapy has been used in immune deficiency diseases for more than 50 years. The indications for this treatment have evolved, however, and IVIG therapy is now used in various diseases in which the immune system plays a prominent role. IVIG therapy has carved out a niche in dermatology for the treatment of such conditions as dermatomyositis, autoimmune bullous diseases, and toxic epidermal necrolysis. Special attention has been paid to this therapy in recent years. New guidelines have been published and should be taken into consideration in dermatology. This review provides a practical guide to IVIG use in our specialty. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Werhagen, Lars; Borg, Kristian
Pain is a common symptom that affects quality of life in patients with post-polio syndrome. An increase in cytokine in the cerebrospinal fluid suggests that inflammation is pathophysiologically important in post-polio syndrome. Intravenous immunoglobulin might therefore be a therapeutic option. The aim of this study was to analyse the effect of intravenous immunoglobulin treatment on pain in post-polio syndrome. An uncontrolled clinical study. Patients with post-polio syndrome and pain (n = 45) underwent a neurological examination and were interviewed about pain before and 6 months after treatment with intravenous immunoglobulin. Pain intensity was measured on a visual analogue scale. The pain was classified according to the International Association for the Study of Pain criteria as neuropathic when it occurred in an area with decreased sensibility, or nociceptive when signs of inflammation and/or painful joints movements were present. After treatment 31/45 (69%) patients were improved, with a mean visual analogue scale decrease from 53 to 42 (p = 0.001). Eighteen patients (40%) had a decrease of 20 or more points on the visual analogue scale. The effect of treatment did not differ regarding age, gender and severity of disability. Two-thirds of 45 patients with post-polio syndrome and pain reported a decrease on the visual analogue scale for pain after treatment with intravenous immunoglobulin, and 40% reported a decrease of 20 or more points on the visual analogue scale.
Full Text Available Abstract A 46 year old woman presented with a one month history of rash and mylagia. The history, clinical findings and blood tests all supported a diagnosis of dermatomyositis. The patient later developed dysphagia and was successfully treated with intravenous immunoglobulin. Investigations and treatment of dysphagia in the context of dermatomyositis are discussed.
Karlsson Annika C
Full Text Available Abstract Background The latency of HIV-1 in resting CD4+ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART. As yet, no approach to reduce this viral reservoir has proven effective. Methods Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4+ T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4+ T-cells were compared with single genome sequencing (SGS of the gag region. T-lymphocyte activation markers and serum interleukins were measured. Results The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA ≥ 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8–12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7 levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma. Conclusion The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4+ T-cells. We propose that IVIG should be further evaluated as an adjuvant
Jun, Jae Sung; Jung, Young Kwon; Lee, Dong Won
Vitamin D is associated with various pathological conditions such as cardiovascular diseases and cancer. We investigated the relationship between vitamin D and Kawasaki disease (KD). We performed a retrospective review of the medical records of patients with KD between February 2013 and March 2016 in Daegu Fatima Hospital. Study participants were grouped according to vitamin D serum concentration. Group 1 included patients with 25(OH)-vitamin D ≥20 ng/mL. Group 2 included patients with 25(OH)-vitamin D immunoglobulin was more frequent in group 2 ( P =0.023). No significant difference in the incidence of coronary artery complications was observed. Low vitamin D levels are associated with resistance to intravenous immunoglobulin therapy in KD. Vitamin D deficiency might be a risk factor for immunoglobulin resistance in KD.
Marsh, E A
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.
Atikan, B. Y.; Koroglu, O. A.; Yalaz, M.; Ergun, O.; Dokumcu, Z.; Doganavasrgil, B.
Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery. (author)
Kuo, Ho-Chang; Liang, Chi-Di; Wang, Chih-Lu; Yu, Hong-Ren; Hwang, Kao-Pin; Yang, Kuender D
Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8-562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.
Ramirez, C; de Sèze, J; Stojkovic, T; Ferriby, D; Delalande, S; Defoort-Dhellemmes, S; Vermersch, P
Acute or sub-acute pure dysautonomia is uncommon. We report a case of sub-acute pure pandysautonomia with favorable outcome after intravenous immunoglobulin therapy. A 29-year-old right-handed student, with an uneventful medical history presented, for one month, bilateral loss of visual acuity and digestive disorders, associating diarrhea, vomiting and anorexia. Physical examination revealed bilateral intrinsec oculomotor nerve palsy, a dryness syndrome and severe orthostatic hypotension. Ophthalmologic examination showed bilateral diffuse parasympathic impairment associating an Argyll Robertson pupil and full pupil light reflex abolition. Elevated protein level (0.93g/l) was the only cerebrospinal fluid anomaly. Serum tests were negative for anti-gangliosides antibodies. The patient improved slowly after two series of intravenous immunoglobulin infusions. Clinical course and laboratory findings suggest that acute or sub-acute pure pandysautonomia events are likely to be related to acute polyradiculoneuritis. Therefore intravenous polyvalent immunoglobulin infusions should be attempted, even if their efficacy needs to be confirmed.
Full Text Available The problem of intrauterine infection (IUI is still relevant today. Ineffective treatment of this pathology is associated with physiological decline of the immunity in these patients. We have proposed the additional use of intravenous immunoglobulin for the treatment of pregnant women with IUI. There were examined 75 patients with IUI, which was diagnosed in the II trimester. The I group consisted of 40 individuals who received conventional treatment, the II group was formed from 35 women who additionally received intravenous immunoglobulin. On the background of IUI, pregnancy was characterized by an increased incidence of threatened miscarriage and premature labor, gestosis and placental dysfunction; during delivery, premature rupture of amniotic membrane and fetal distress were more common. These patients had placenta with both ultrasonic and histological signs of infection. Among newborns, there was a significant increase in the incidence of pathology associated with intrauterine infection. Additional use of intravenous immunoglobulin in the treatment of IUI during the II trimester of pregnancy in comparison with conventional therapy leads to a significant reduction in the incidence of both obstetric complications and perinatal pathology.
Elovaara, I.; Apostolski, S.; Doorn, P. van
and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain-Barre syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG...
Full Text Available BACKGROUND: Polymorphonuclear neutrophils (PMN play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. CONCLUSIONS/SIGNIFICANCE: IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.
van Schaik, I. N.; Vermeulen, M.; Brand, A.
Intravenous immunoglobulin is used in inflammatory demyelinating diseases of the peripheral as well as the central nervous system. It is not known which mechanism(s) accounts for the beneficial effect observed in these diseases. The immunomodulatory effects of IVIg in two different models of T and B
Basta, M; Branch, D R
Although intravenous immunoglobulin (IVIg) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti-inflammatory effects may be facilitated by IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes. © 2014 British Society for Immunology.
Full Text Available After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.
Aswine K. Bal
Conclusion: The results of this study suggest that although IVIG treatment within 10 days is important to minimize development of cardiac pathology, neither occurrence of CA lesions in IVIG-treated children nor the time frame for resolution of established CA abnormalities was associated with the timing of IVIG administration. Age 40 mm/hour predict a delay in resolution of CA lesions among children with KD.
Full Text Available Single-nucleotide polymorphisms (SNPs in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229 and caspase-3 (CASP3, rs113420705 are associated with susceptibility to KD in Japanese and Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG resistance and coronary artery lesion (CAL in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model. A combinatorial association between ITPKC (rs28493229 and CASP3 (rs113420705 was found in CAL formation (P = 0.0227, OR: 3.06. KD patients with high-risk genotype had a trend of overrepresentation in IVIG resistance compared with individual SNPs. Our findings suggest the existence of genetic factors affecting patients' risk for CAL formation and IVIG responsiveness in a Taiwanese population.
Yap, P L
A number of episodes of non-A, non-B hepatitis (NANB) have been associated in the recent past with the administration of intravenous immunoglobulin (IGIV). It now appears that hepatitis C virus (HCV) is the cause of NANB, although not all the factors leading to HCV transmission by IGIV are completely understood. Nevertheless, based on a retrospective analysis of two episodes of HCV transmitted by anti-Rh D immunoglobulin (anti-D), cold ethanol fractionation clearly is important in ensuring viral safety; both of these intravenous anti-D preparations were manufactured without benefit of this purification step. Other episodes of HCV transmission have been associated with IGIV produced using chromatography (particularly DEAE-Sephadex chromatography), which has been used after cold ethanol fractionation to further purify immunoglobulin G. DEAE-Sephadex chromatography may have only a marginal partitioning capacity, such that infective HCV virions are not further fractionated into waste fractions. All IGIV preparations associated with HCV transmission were formulated as lyophilized preparations, which may be important in stabilizing HCV before administration to patients. The role of anti-HCV screening in improving the viral safety of IGIV preparations remains unclear, but additional viral inactivation steps, such as solvent-detergent treatment or incubation at pH 4.0, probably are required for IGIV manufactured using chromatographic procedures.
Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko
Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.
Ahmed Sahly MD
Full Text Available Nonparaneoplastic opsoclonus–myoclonus ataxia syndrome is a rare neuroinflammatory condition featured by opsoclonus, myoclonus, ataxia, and cognitive behavioral disturbance. The authors report an observation of enterovirus 71-associated opsoclonus–myoclonus ataxia syndrome evolving toward full recovery on intravenous intravenous immunoglobulin (IG treatment. Based on this case report, enterovirus 71 should be added to the list of infectious agents likely involved in opsoclonus–myoclonus ataxia syndrome, including the emerging subgroup of opsoclonus–myoclonus ataxia syndrome recovering without aggressive or prolonged immunosuppressive intervention. Further studies are mandatory to define the precise role, incidence, treatment, and outcome of enterovirus 71 and other infectious agents in benign forms of opsoclonus–myoclonus ataxia syndrome.
Pullarkat, Vinod A.; Gernsheirner, Terry B.; Wasser, Jeffrey S.; Newland, Adrian; Guthrie, Troy H.; de Wolf, Joost Th. M.; Stewart, Ron; Berger, Dietmar
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
Endo, L M; Giannobile, J V; Dobbs, A K; Foote, J B; Szymanska, E; Warnock, D G; Cook, W J; Conley, M E; Schroeder, H W
Immune complex deposition in the subepithelial zone of glomerular capillaries can lead to membranous glomerulopathy. To present the case of a 23-year-old man with X-linked agammaglobulinemia (XLA) who developed idiopathic membranous glomerulopathy while receiving intravenous immunoglobulin (IVIG). We performed an immunological workup, genetic testing, and a renal biopsy. XLA was confirmed with less than 0.02% CD19+ cells in the blood after sequence analysis revealed a nonfunctional BTK gene. The patient presented with microhematuria, which persisted for 3 years and spanned treatment with 5 different preparations of intravenous gammaglobulin. Immunohistochemistry revealed membranous glomerulopathy. Although endogenous serum immunoglobulin (Ig) production is severely impaired in XLA, rare B lymphocytes that have managed to mature can produce functional IgG antibodies. The pathogenic immune complexes could reflect IVIG reacting with polymorphic autoantigens, an endogenous IgG-producing clone reacting with a common idiotype present in the IVIG, or both.
Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.
Ravindranath, M H; Terasaki, P I; Maehara, C Y; Jucaud, V; Kawakita, S; Pham, T; Yamashita, W
Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg. © 2014 British Society for Immunology.
Vehapoğlu, Aysel; Göknar, Nilüfer; Tuna, Rümeysa; Çakır, Fatma Betül
Drug-induced hemolytic anemia is an immune-mediated phenomenon that leads to the destruction of red blood cells. Here, we present a case of life-threatening ceftriaxone-induced hemolytic anemia (CIHA) in a previously healthy 3-year-old girl. We also reviewed the literature to summarize the clinical features and treatment of hemolytic anemia. Acute hemolysis is a rare side effect of ceftriaxone therapy associated with high mortality. Our patient had a sudden loss of consciousness with macroscopic hematuria and her hemoglobin dropped from 10.2 to 2.2 g/dl over 4 hours, indicating that the patient had life-threatening hemolysis after an intravascular dose of ceftriaxone who had previously been treated with ceftriaxone in intramuscular form for six days. CIHA is associated with a positive direct antiglobulin test, revealing the presence of IgG in all cases and C3d in most cases. Our patient's direct antiglobulin test was positive for IgG (3+) and for C3d (4+). The case was managed successfully with supportive measures and intravenous immunoglobulin therapy. Ceftriaxone is used very frequently in children; an early diagnosis and proper treatment of hemolytic anemia are essential to improve the patient outcome. The pathophysiological mechanism is the same as for non-drug autoimmune hemolytic anemia. However, there is still no consensus treatment for CIHA. Intravenous immunoglobulin can be used in clinical emergencies, such as our case, or in refractory cases.
Sanchez-Ramon, Silvia; Corbi, Angel L; Fidalgo, Agueda Garcia; Dominguez-Soto, Angeles
Cumulative recent evidence from clinical trials, observational studies and case reports has shown that subcutaneous administration of immunoglobulin (SCIg) exerts similar immunomodulatory capacity than intravenous immunoglobulin (IVIg) in autoimmune neurological diseases. Besides the beneficial clinical effects, the profile of safety and autonomy for the patient is higher for SCIg, while it is cost-saving in terms of the health resources used. However, there are still very few approved indications for SCIg and a certain resistance to choose SCIg for other autoimmune conditions even despite patients' interests. Here we present an updated review of the known immunomodulatory mechanisms of action of Ig and the current hypothesis supporting the clinical and immunological advantages of SCIg over IVIg that derive from their specific pharmacokinetic features. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Rakesh Tilak Raj
Full Text Available There is a high mortality rate in Stevens Johnson Syndrome (SJS and it ranges between 5%-15%. At present, there is no definite consensus regarding treatment in SJS although the effectiveness of intravenous immunoglobulin’s (IVIg and immunosuppressive like cyclosporine have generated new hopes in the lives of these patients. But the options of combination therapy of steroids, IVIg and Placentrex gel have not been fully exercised in SJS. Henceforth, we report a case of Nimesulide induced SJS; managed successfully with a combined approach without any recurrence during a 12 months follow-up.
N. A. Suponeva
Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.
Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.
Sugimoto, Keisuke; Nishi, Hitomi; Miyazawa, Tomoki; Wada, Norihisa; Izu, Akane; Enya, Takuji; Okada, Mitsuru; Takemura, Tsukasa
Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). A 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary β2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary β2-MG and serum creatinine concentrations improved. Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane.
Full Text Available Objective. Kawasaki disease (KD is an acute systematic vasculitis in children which causes coronary arterial lesions and hydrops of gallbladder. Our objective is to correlate the clinical significance and influence on disease outcome of patients with gallbladder abnormalities in Kawasaki dissease. Methods. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients with abdominal sonography were divided into 2 groups based on the absence (Group A, N=61 or presence (Group B, N=16 of gallbladder abnormalities (GBA, defined as hydrops or acalculous cholecystitis. Between the two groups, clinical features, demographic data (including admission days, coronary artery lesions, IVIG resistance, and laboratory data before/after IVIG treatment were collected for analysis. Results. The presence of sonographic gallbladder abnormalities is correlated with higher levels of serum CRP, GPT, and neutrophils. It also points to an increased number of IVIG resistance rates in group B. There was no significant statistical difference among clinical features, age, gender, admission days, or coronary artery lesions between the two groups. Conclusion. Sonographic gallbladder abnormalities are associated with higher CRP, GPT, neutrophil and IVIG resistance in KD. It can be used as a predictor of IVIG resistance in patients with KD.
Full Text Available Intravenous Immunoglobulin (IVIG has been proposed as a potential therapeutic for Alzheimer's disease (AD and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ-specific antibodies (pAbs-Aβ on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies.
Full Text Available A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation.
Full Text Available Miller-Fisher syndrome (MFS is a rare condition characterized by the classical triad of ophthalmoplegia, ataxia, and areflexia (Fisher, 1956. It is considered a variant of Guillain-Barré syndrome (GBS with which it may overlap, or it can occur in more limited forms. We report a case of a thirty-five-year-old male who presented with a six-day history of diplopia, following a recent chest infection. On examination, he was found to have bilateral sixth nerve palsy, bilateral fourth nerve palsy, bilateral areflexical mydriasis, ataxia and total absence of reflexes. After excluding other conditions, a diagnosis of Miller-Fisher syndrome was made. The patient was administered intravenous immunoglobulin and made an uneventful recovery.
González-Castillo, Z; Solórzano Gómez, E; Torres-Gómez, A; Venta Sobero, J A; Gutiérrez Moctezuma, J
Epilepsy is the most common neurological disease in childhood; depending on the definition of drug-resistant epilepsy, incidence varies from 10% to 23% in the paediatric population. The objective of this study was to account for the decrease in the frequency and/or monthly duration of epileptic seizures in paediatric patients with drug-resistant epilepsy treated with antiepileptic drugs, before and after adding intravenous immunoglobulin G (iIV IgG). This is an analytic, observational, retrospective case-control study. We studied paediatric patients with drug-resistant epilepsy who were treated with IV IgG at the Centro Médico Nacional 20 de Noviembre, in Mexico City, from 2003 to 2013. One hundred and sixty seven patients (19.5%) had drug-resistant epilepsy and 44 (5.1%) started adjuvant treatment with IV IgG. The mean age of patients at the beginning of treatment was 6.12 years±5.14); aetiology was structural acquired in 28 patients (73.6%), genetic in 5 (13.1%), immune in 1 (2.6%), and unknown in 4 (10.5%). At 2 months from starting IV IgG, seizure duration had reduced to 66.66%; the frequency of seizures was reduced by 64% at 4 months after starting treatment (P<.001). According to the results of this study, intravenous immunoglobulin may be an effective therapy for reducing the frequency and duration of seizures in paediatric patients with drug-resistant epilepsy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Gadian, Jonathan; Kirk, Emma; Holliday, Kate; Lim, Ming; Absoud, Michael
A systematic literature review of intravenous immunoglobulin (IVIG) treatment of paediatric neurological conditions was performed to summarize the evidence, provide recommendations, and suggest future research. A MEDLINE search for articles reporting on IVIG treatment of paediatric neuroinflammatory, neurodevelopmental, and neurodegenerative conditions published before September 2015, excluding single case reports and those not in English. Owing to heterogeneous outcome measures, meta-analysis was not possible. Findings were combined and evidence graded. Sixty-five studies were analysed. IVIG reduces recovery time in Guillain-Barré syndrome (grade B). IVIG is as effective as corticosteroids in chronic inflammatory demyelinating polyradiculoneuropathy (grade C), and as effective as tacrolimus in Rasmussen syndrome (grade C). IVIG improves recovery in acute disseminated encephalomyelitis (grade C), reduces mortality in acute encephalitis syndrome with myocarditis (grade C), and improves function and stabilizes disease in myasthenia gravis (grade C). IVIG improves outcome in N-methyl-d-aspartate receptor encephalitis (grade C) and opsoclonus-myoclonus syndrome (grade C), reduces cataplexy symptoms in narcolepsy (grade C), speeds recovery in Sydenham chorea (grade C), reduces tics in selected cases of Tourette syndrome (grade D), and improves symptoms in paediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (grade B). IVIG is a useful therapy in selected neurological conditions. Well-designed, prospective, multi-centre studies with standardized outcome measures are required to compare treatments. © 2016 Mac Keith Press.
Warnatz, K; Ballow, M; Stangel, M; Bril, V
The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use. © 2014 British Society for Immunology.
Jakobsen, Johannes Klitgaard; Markvardsen, Lars Høj; Harbo, Thomas
Objective: We hypothesised that the effect of subcutaneous infusion of immunoglobulins(SCIG) on muscular performance in chronic inflammatory demyelinating polyneuropathy(CIDP) is superior to that of placebo and equals the therapeutic effect of intravenous infusion(IVIG). Background Subcutaneous...... treatment with large amounts of immunoglobulins in multifocal motor neuropathy is feasible, safe and effective. In CIDP case reports indicate its therapeutic usefullness as well. Design/Methods: Subjects in IVIG maintenace therapy full-filling the EFNS/PNS criteria for CIDP were considered for participation......G at a concentration of 1.6g/10cc or subcutaneous saline in a double-blinded fashion. Infusions were given twice or thrice weekly for 12 weeks at home. The amount of immunoglobulin corresponded to the clinically predetermined dose. The first subcutaneous infusion was delivered two weeks after the last IVIG treatment...
Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.
Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment
Full Text Available Suzanne Skoda-Smith, Troy R Torgerson, Hans D OchsSeattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, WashingtonAbstract: Antibody deficiency is the most frequently encountered primary immunodeficiency disease (PIDD and patients who lack the ability to make functional immunoglobulin require life-long replacement therapy to prevent serious bacterial infections. Human serum immunoglobulin manufactured from pools of donated plasma can be administered intramuscularly, intravenously or subcutaneously. With the advent of well-tolerated preparations of intravenous immunoglobulin (IVIg in the 1980s, the suboptimal painful intramuscular route of administration is no longer used. However, some patients continued to experience unacceptable adverse reactions to the intravenous preparations, and for others, vascular access remained problematic. Subcutaneously administered immunoglobulin (SCIg provided an alternative delivery method to patients experiencing difficulties with IVIg. By 2006, immunoglobulin preparations designed exclusively for subcutaneous administration became available. They are therapeutically equivalent to intravenous preparations and offer patients the additional flexibility for the self-administration of their product at home. SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life.Keywords: subcutaneous immunoglobulin, primary immunodeficiency disease, antibody deficiency, X-linked agammaglobulinemia, common variable immune deficiency
Jorquera, J I
Flebogamma 5% dual inactivation and filtration (DIF), a new 5% liquid intravenous immunoglobulin with a stability of 2 years when stored at temperatures between 2 and 30 degrees C, has been developed. This new product is the result of the accumulated experience provided by Flebogamma, with more than 30 million grams administered since 1992 in Europe and the United States, and the implementation of the latest technology to improve Flebogamma even more by increasing its viral safety margin further. In addition to the specific inactivation stage for Flebogamma 5% (pasteurization), the new process includes a solvent-detergent treatment and nanofiltration through a Planova filter down to 20 nm. The preparation presents a mean purity of 99.6 +/- 0.2% with a correct chromatographic profile. Percentage values of immunoglobulin (Ig)G subclasses are equivalent to the physiological values of normal serum. The content in IgA as well as other possible impurities is very low, and the product presents a mean result of 109 +/- 5% in the Fc fragment functionality assay, demonstrating the integrity of the IgG molecule. The functionality is also reflected in neutralization tests carried out against poliomyelitis, diphtheria, measles and vaccinia which, apart from the antibody titres determined by enzyme-linked immunosorbent assay, guarantees that antibodies are capable of reacting against these pathogens. Regarding safety, the combination of multiple methods with capacity to inactivate or remove biological agents which include chemical inactivation, heat inactivation, nanofiltration and precipitations, with very different mechanisms of action, provides Flebogamma 5% DIF very wide margins of safety regarding to potential pathogens.
Elsterová, Jana; Palus, Martin; Širmarová, J.; Kopecký, J.; Niller, H.H.; Růžek, Daniel
Roč. 8, č. 2 (2017), s. 253-258 ISSN 1877-959X R&D Projects: GA MZd(CZ) NV16-34238A Institutional support: RVO:60077344 Keywords : flavivirus * ticks * neutralizing antibodies * ivig * antibody-dependent enhancement * ammunotherapy Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.230, year: 2016
Markvardsen, Lars H; Christiansen, Ingelise; Andersen, Henning
and could be an alternative in patients experiencing side effects. Fifty-nine patients diagnosed with neurological disorders (chronic inflammatory demyelinating polyneuropathy (CIDP), multi-focal motor neuropathy (MMN) or post-polio syndrome) were treated with IVIG, and 27 CIDP or MMN patients with SCIG...
Síndrome de Guillain-Barré com flutuações relacionadas ao tratamento com imunoglobulina humana endovenosa (curso trifásico: relato de caso Fluctuations in Guillain-Barré syndrome related to treatment with intravenous human immunoglobulin (trifasic course: case report
MÁRIO EMÍLIO DOURADO
Full Text Available Os autores apresentam um caso de síndrome de Guillain-Barré (SGB, com tetraplegia e ventilação mecânica, que foi tratado com imunoglobulina humana endovenosa (IgEV, 2 g/kg, apresentando melhora clínica inicial, tendo piorado na segunda semana. Foi realizada uma segunda sessão de IgEV, também com melhora inicial, seguida de piora aos 65 dias de doença. Uma terceira etapa de IgEV foi realizada, sendo a melhora definitiva e sem outros episódios após 3 anos de seguimento. Os autores revisam a literatura sobre flutuações relacionadas ao tratamento. Concluem que na SGB é importante uma observação clínica rigorosa nas primeiras semanas após tratamento com IgEV e que seriam necessários estudos para elaborar protocolos alternativos de prevenção nesses casos.The authors report the case of a patient with severe Guillain-Barré syndrome (tetraplegic and on mechanical ventilation, that was treated with intravenous immunoglobulin (IVIg, 2 g/Kg. At first, there was clinical improvement, followed by clinical deterioration two weeks later. On the second course of IVIg there was, again, clinical improvement and then deterioration, 65 days after treatment. Finally, on the third course of treatment definitive recovery was achieved and no more relapses happened so far (three years after the treatment. The authors review the literature about fluctuations related to treatment with IVIg. Conclusions are that these patients should be closely observed during the first weeks after IVIg treatment, and that further studies are still necessary to elaborate alternative protocols on the prevention of these cases.
Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial.
de Alarcon, Pedro A; Matthay, Katherine K; London, Wendy B; Naranjo, Arlene; Tenney, Sheena C; Panzer, Jessica A; Hogarty, Michael D; Park, Julie R; Maris, John M; Cohn, Susan L
No previous clinical trial has been conducted for patients with neuroblastoma associated opsoclonus myoclonus ataxia syndrome (OMA), and current treatment is based on case reports. To evaluate the OMA response to prednisone and risk-adapted chemotherapy and determine if the addition of intravenous gammaglobulin (IVIG) further improves response, the Children's Oncology Group designed a randomized therapeutic trial. Eligible subjects were randomized to receive twelve cycles of IVIG (IVIG+) or no IVIG (NO-IVIG) in addition to prednisone and neuroblastoma risk-adapted chemotherapy. All low-risk patients were treated with cyclophosphamide. The severity of OMA symptoms was evaluated at 2, 6, and 12 months using a scale developed by Mitchell and Pike and baseline versus best response scores were compared. A single patient who did not undergo neurologic assessment was excluded from OMA response analysis. This study is registered with Clinical Trials.gov (identifier NCT00033293). Of the 53 patients enrolled in the study, 62% (33/53) were female. There were 44 low-risk, 7 intermediate-risk, and 2 high-risk neuroblastoma patients. Twenty-six subjects were randomized to receive IVIG+ and 27 were randomized to NO-IVIG. The neuroblastoma 3-year event-free survival (95% confidence interval (CI)) was 94.1% (87.3%, 100%) and overall survival was 98.0% (94.1%, 100%). Significantly higher rates of OMA response were observed in patients randomized to IVIG+ compared to NO-IVIG [21/26=80.8% for IVIG+; 11/27=40.7% for NO-IVIG (odds ratio=6.1; 95% CI: (1.5, 25.9), p=0.0029)]. For the majority of patients, the IVIG+ OMA regimen combined with cytoxan or other risk-based chemotherapy was well tolerated, although there was one toxic death in a high-risk subject. This is the only randomized prospective therapeutic clinical trial in children with neuroblastoma-associated OMA. The addition of IVIG to prednisone and risk-adapted chemotherapy significantly improves OMA response rate. IVIG
Erdem, Elif; Kocabas, Emine; Taylan Sekeroglu, Hande; Ozgür, Ozlem; Yagmur, Meltem; Ersoz, T Reha
A 7-year-old girl had presented with high body temperature and joint pain which continued for 3 days. Because of the prolonged history of unexplained fever, rash, bilateral nonpurulent conjunctival injection, oropharyngeal erythema, strawberry tongue, and extreme of age, incomplete Kawasaki disease was considered and started on an intravenous immunoglobulin infusion. Six days after this treatment, patient was referred to eye clinic with decreased vision and photophobia. Visual acuity was reduced to 20/40 in both eyes. Slit-lamp examination revealed bilateral diffuse corneal punctate epitheliopathy and anterior stromal haze. Corneal epitheliopathy seemed like crystal deposits. One day after presentation, mild anterior uveitis was added to clinical picture. All ocular findings disappeared in one week with topical steroid and unpreserved artificial tear drops. We present a case who was diagnosed as incomplete Kawasaki disease along with bilateral diffuse crystalline-like keratopathy. We supposed that unusual ocular presentation may be associated with intravenous immunoglobulin treatment.
Full Text Available A 7-year-old girl had presented with high body temperature and joint pain which continued for 3 days. Because of the prolonged history of unexplained fever, rash, bilateral nonpurulent conjunctival injection, oropharyngeal erythema, strawberry tongue, and extreme of age, incomplete Kawasaki disease was considered and started on an intravenous immunoglobulin infusion. Six days after this treatment, patient was referred to eye clinic with decreased vision and photophobia. Visual acuity was reduced to 20/40 in both eyes. Slit-lamp examination revealed bilateral diffuse corneal punctate epitheliopathy and anterior stromal haze. Corneal epitheliopathy seemed like crystal deposits. One day after presentation, mild anterior uveitis was added to clinical picture. All ocular findings disappeared in one week with topical steroid and unpreserved artificial tear drops. We present a case who was diagnosed as incomplete Kawasaki disease along with bilateral diffuse crystalline-like keratopathy. We supposed that unusual ocular presentation may be associated with intravenous immunoglobulin treatment.
Full Text Available Immunoglobulin G (IgG of excellent quality for intravenous use was obtained from the cryosupernatant of human plasma by a chromatographic method based on a mixture of ion-exchange, DEAE-Sepharose FF and arginine Sepharose 4B affinity chromatography and a final purification step by Sephacryl S-300 HR gel filtration. The yield of 10 experimental batches produced was 3.5 g IgG per liter of plasma. A solvent/detergent combination of 1% Tri (n-butyl phosphate and 1% Triton X-100 was used to inactivate lipid-coated viruses. Analysis of the final product (5% liquid IgG based on the mean for 10 batches showed 94% monomers, 5.5% dimers and 0.5% polymers and aggregates. Anticomplementary activity was 0.3 CH50/mg IgG and prekallikrein activator levels were less than 5 IU/ml. Stability at 37ºC for 30 days in the liquid state was satisfactory. IgG was stored in flasks (2.5 g/flask at 4 to 8ºC. All the characteristics of the product were consistent with the requirements of the 1997 Pharmacopée Européenne.
Egerup, Pia; Lindschou, Jane; Gluud, Christian
, and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled......BACKGROUND: Recurrent miscarriage is generally defined as three or more miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all women and the condition can only be explained by parental chromosome abnormalities, uterine malformations, or endocrine or thrombophilic...... randomised placebo-controlled trials, with opposing results, investigating intravenous immunoglobulins with a total of 324 recurrent miscarriage patients have been published. METHODS: We will include randomised clinical trials irrespective of publication date, publication type, publication language...
Tatyana V. Sleptsova
Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.
Qin, Wei; Huang, Shao-Ling; Li, Ting-Ting
To investigate the clinical effect and safety of anti-D immunoglobulin (anti-D) in the treatment of children with newly diagnosed acute immune thrombocytopenia (ITP) through a Meta analysis. PubMed, EMBASE, Cohrane Library, Ovid, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) published up to April 2017. Review Manager 5.3 was used for the Meta analysis. Seven RCTs were included. The Meta analysis showed that after 72 hours and 7 days of treatment, the intravenous immunoglobulin (IVIG) group had a significantly higher percentage of children who achieved platelet count >20×10 9 /L than the anti-D group (Panti-D (50 μg/kg) group and the IVIG group (P>0.05), and there were also no significant differences in platelet count after 24 hours and 7 days of treatment between the 50 μg/kg and 75 μg/kg anti-D groups (P>0.05). The anti-D group had a significantly greater reduction in the hemoglobin level than the IVIG group after treatment, but did not need transfusion. No children in the anti-D group or the IVIG group experienced serious adverse reactions. Intravenous injection of anti-D may have a similar effect as IVIG in improving platelet count in children with acute ITP, but it may be slightly inferior to IVIG in the rate of platelet increase after treatment. The anti-D dose of 50 μg/kg may have a similar effect as 75 μg/kg. The recommended dose of anti-D for treatment of ITP is safe.
Full Text Available BACKGROUND: The etiology of Kawasaki Disease (KD is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5 and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL and response to intravenous immunoglobulin (IVIG in Japanese children, who have the highest incidence of KD, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., four copies was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR=2.25, p=0.004 and OR=6.26, p=0.089, respectively. Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026 and CAL development (OR=0.44, p=0.071. CONCLUSIONS/SIGNIFICANCE: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.
Full Text Available Common variable immunodeficiency is the most common form of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment of these patients. By using a differential proteomic approach based on 2D-DIGE, we examined serum samples from normal donors and from matched, naive, and immunoglobulin-treated patients. The results highlighted regulated expression of serum proteins in naive patients. Among the identified proteins, clusterin/ApoJ serum levels were lower in naive patients, compared to normal subjects. This finding was validated in a wider collection of samples from newly enrolled patients. The establishment of a cellular system, based on a human hepatocyte cell line HuH7, allowed to ascertain a potential role in the regulation of CLU gene expression by immunoglobulins.
Full Text Available INTRODUCTION: Different immunoglobulin manufacturing processes may influence its effectiveness for Kawasaki disease. However, nationwide studies with longitudinal follow-up are still lacking. The aim of this study was to evaluate the comparative effectiveness of immunoglobulin preparations from a nationwide perspective. MATERIALS AND METHODS: This is a nationwide retrospective cohort study with a new user design. Data came from the National Health Insurance Research Database of Taiwan. From 1997 to 2008, children under 2 years old who received immunoglobulin therapy for the first time under the main diagnosis of Kawasaki disease were enrolled. The manufacturing processes were divided into β-propiolactonation, acidification and those containing IgA. The endpoints were immunoglobulin non-responsiveness, acute aneurysm, prolonged use of anti-platelets or anti-coagulants, and recurrence. RESULTS: In total, 3830 children were enrolled. β-propiolactonation had a relative risk of 1.45 (95% CI 1.08~1.94 of immunoglobulin non-responsiveness, however, the relative risks for acidification and containing IgA were non-significant. For acute aneurysms, acidification had a relative risk of 1.49 (95% CI 1.17~1.90, however the relative risks for β-propiolactonation and containing IgA were non-significant. For prolonged use of anti-platelets or anti-coagulants, β-propiolactonation had a relative risk of 1.44 (95% CI 1.18~1.76, and acidification protected against them both with a relative risk of 0.82 (95% CI 0.69~0.97, whereas the relative risk for containing IgA was non-significant. For recurrence, all three factors were non-significant. CONCLUSIONS: The effectiveness of immunoglobulin may differ among different manufacturing processes. β-propiolactonation had a higher risk of treatment failure and prolonged use of anti-platelets or anti-coagulants. Acidification may increase the risk of acute coronary aneurysms.
Triguero, D.; Buciak, J.L.; Pardridge, W.M.
Cationization of proteins in general enhances the cellular uptake of these macromolecules, and cationized antibodies are known to retain antigen binding properties. Therefore, cationized antibodies may be therapeutic and allow for intracellular immunization. The present studies test the hypothesis that the tissue uptake of cationized immunoglobulin G (IgG) after intravenous administration may be greatly increased relative to the uptake of native proteins. The pharmacokinetics of cationized immunoglobulin G clearance from blood, and the volume of distribution of the cationized or native protein (albumin, IgG) for 10 organs was measured both in anesthetized rats and in an anesthetized adult Macaca irus cynomologous monkey. Initial studies on brain showed that serum factors inhibited uptake of 125I-cationized IgG, but not 3H-cationized IgG. The blood-brain barrier permeability surface area product for 3H-cationized IgG was 0.57 ± 0.04 microliters min-1 g-1. The ratio of the volume of distribution of the 3-H-cationized IgG compared to 3H-labeled native albumin ranged from 0.9 (testis) to 15.7 (spleen) in the rat at 3 hr after injection, and a similarly enhanced organ uptake was observed in the primate. In conclusion, these studies demonstrate that cationization of immunoglobulin greatly increases organ uptake of the plasma protein compared to native immunoglobulins, and suggest that cationization of monoclonal antibodies may represent a potential new strategy for enhancing the intracellular delivery of these proteins
Zwiers, Carolien; Scheffer-Rath, Mirjam Ea; Lopriore, Enrico; de Haas, Masja; Liley, Helen G
Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to
Markvardsen, L H; Sindrup, S H; Christiansen, I; Olsen, N K; Jakobsen, J; Andersen, H
Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP. Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests. All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related. In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment. © 2016 EAN.
Nomura, Hisashi; Honda, Haruki; Egami, Shohei; Yokoyama, Tomoaki; Fujimoto, Atsushi; Ishikawa, Makiko; Sugiura, Makoto
Intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma are therapeutic options for patients with refractory pemphigus vulgaris. Passive acquisition of various clinically important antibodies through these therapies can occur, leading to false serology and negatively affecting patients' clinical care. It is recommended that dermatologists recognize the possibility of these phenomena and interpret them appropriately. Here, we report false-positive serology following intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma in a patient with refractory pemphigus vulgaris. We also discuss the measure for misinterpretation and unnecessary clinical intervention. © 2015 Japanese Dermatological Association.
Hoekstra, PJ; Minderaa, RB; Kallenberg, CGM
Background: Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections. No data are available on the effectiveness of intravenous
Bleeker, W. K.; Teeling, J. L.; Verhoeven, A. J.; Rigter, G. M.; Agterberg, J.; Tool, A. T.; Koenderman, A. H.; Kuijpers, T. W.; Hack, C. E.
Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found
Caro, X J; Winter, E F; Dumas, A J
The aetiopathogenesis of the fibromyalgia syndrome (FMS) remains unknown. Recent reports, however, suggest that a subgroup of FMS subjects has an immune-mediated disease. Therefore, our primary objective was to study FMS subjects for evidence of an immune-mediated demyelinating polyneuropathy. Our secondary objective was to determine the effects of treating these FMS subjects with the immune modulator, intravenous immunoglobulin (IVIg). Fifty-eight FMS subjects, 26 rheumatic non-FMS subjects and 52 non-rheumatic non-FMS subjects were studied. Subjective measures of paraesthesias, weakness, stocking hypaesthesia, pain, fatigue and stiffness were made. Objective measures of tenderness, proximal muscle strength and electrodiagnostic (EDX) evidence of polyneuropathy and demyelination were also made. Eleven other FMS subjects underwent sural nerve biopsy. Paraesthesias, subjective weakness and stocking hypaesthesia were more common in FMS than in rheumatic non-FMS (P < or = 0.0001). Proximal muscle strength was less in FMS than in rheumatic non-FMS (P < or = 0.0001). EDX demonstrated a distal demyelinating polyneuropathy, suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP), in 33% of FMS subjects. No rheumatic non-FMS subject had polyneuropathy (P = 0.005), or demyelination (P = 0.05). Fifteen FMS/CIDP subjects were subsequently treated with IVIg (400 mg/kg each day for 5 days). Pain (P = 0.01), tenderness (P = 0.001) and strength (P = 0.04) improved significantly. Fatigue and stiffness trended towards improvement. A significant subset of FMS subjects have clinical and EDX findings suggestive of CIDP. IVIg treatment shows promise in treating this subset. These observations have implications for better understanding and treating some FMS patients.
Markvardsen, Lars Høj; Christiansen, Ingelise; Jakobsen, Johannes
dosage. IVIG was administered two to three times for 6 weeks. Two weeks after the last IVIG infusion at Week 8, SCIG was initiated with injections twice or thrice weekly until Week 20. Blood samples were drawn 2 weeks after IVIG at Weeks 2 and 8 and during SCIG at Weeks 14 and 20 determining hemoglobin...
Full Text Available La sindrome di Churg-Strauss è una malattia estremamente rara e ancora più raro è riscontrarla in una paziente in stato di gravidanza. Il trattamento iniziale della malattia consiste nella somministrazione di alte dosi di corticosteroidi. I pazienti più gravi o che rispondono poco o insoddisfacientemente ai corticosteroidi vengono solitamente trattati con farmaci citotossici. Le immunoglobuline somministrate per via endovenosa (IgEV stanno dimostrando di essere efficaci nel trattamento di questa patologia, tuttavia non esiste un consenso universale sulla loro effettiva utilità nelle vasculiti sistemiche. Noi presentiamo il caso di una donna con sindrome di Churg-Strauss resistente al trattamento con corticosteroidi e ciclofosfamide. Allorché si riscontrò che la paziente era al 3° mese di gravidanza fu iniziata una terapia con alte dosi di IgEV con ottimi risultati. Questo caso conferma l’utilità del trattamento con IgEV della sindrome di Churg-Strauss e ne dimostra l’efficacia anche in stato di gravidanza.
Teksam, M.; Tali, T.; Isik, S.; Kocer, B.
We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)
Lachmann, R. A.; van Kaam, A. H. L. C.; Haitsma, J. J.; Verbrugge, S. J. C.; Delreu, F.; Lachmann, B.
Mechanical ventilation is known to induce bacterial translocation from the lung into the systemic circulation. This study determined the effect of immunoglobulin M (IgM)-enriched polyclonal immunoglobulins on bacteremia due to ventilation-induced translocation in an acute respiratory distress
Full Text Available Herpes simplex virus 1 (HSV encephalitis (HSE has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS inflammatory responses. We hypothesized that CNS inflammation is casually involved in behavioral abnormalities after HSE and that treatment with ACV and pooled human immunoglobulin (IVIG, an immunomodulatory drug, would improve outcomes compared to mice treated with phosphate buffered saline (PBS or ACV alone. Anxiety levels were high in HSV-infected PBS and ACV-treated mice compared to mice treated with ACV + IVIG, consistent with reports implicating inflammation in anxiety induced by lipopolysaccharide (LPS or stress. Female, but not male, PBS-treated mice were cognitively impaired, and unexpectedly, ACV was protective, while the inclusion of IVIG surprisingly antagonized ACV’s beneficial effects. Distinct serum proteomic profiles were observed for male and female mice, and the antagonistic effects of ACV and IVIG on behavior were paralleled by similar changes in the serum proteome of ACV- and ACV + IVIG-treated mice. We conclude that inflammation and other factors mediate HSV-induced behavioral impairments and that the effects of ACV and IVIG on behavior involve novel mechanisms.
Berger, Melvin; Pinciaro, Paul J; Althaus, Arthur; Ballow, Mark; Chouksey, Akhilesh; Moy, James; Ochs, Hans; Stein, Mark
Flebogamma 10% DIF represents an evolution of intravenous immune globulin from the previous 5% product to be administered at higher rates and with smaller infusion volumes. Pathogen safety is enhanced by the combination of multiple methods with different mechanisms of action. The objective of this study as to evaluate the efficacy, pharmacokinetics, and safety of Flebogamma 10% DIF for immunoglobulin replacement therapy in primary immunodeficiency diseases (PIDD). Flebogamma 10% DIF was administered to 46 subjects with well-defined PIDD at a dose of 300-600 mg/kg every 21-28 days for 12 months. Serious bacterial infection rate was 0.025/subject/year. Half-life in serum of the administered IgG was approximately 35 days. No serious treatment-related adverse event (AE) occurred in any patient. Most of the potentially treatment-related AEs occurred during the infusion, accounting for 20% of the 601 infusions administered. Flebogamma 10% DIF is efficacious and safe, has adequate pharmacokinetic properties, and is well-tolerated for the treatment of PIDD.
Caballero, Santiago; Nieto, Sandra; Gajardo, Rodrigo; Jorquera, Juan I
A new human liquid intravenous immunoglobulin product, Flebogamma DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log(10) TCID(50)) or Plaque Forming Units assay (log(10) PFU). Validation studies demonstrated that each specific step cleared more than 4 log(10) for all viruses assayed. An overall viral clearance between > or =13.33 log(10) and > or =25.21 log(10), was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma DIF has a very high viral safety profile. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
Tiraboschi, J; Ray, S; Patel, K; Teague, A; Pace, M; Phalora, P; Robinson, N; Hopkins, E; Meyerowitz, J; Wang, Y; Cason, J; Kaye, S; Sanderson, J; Klenerman, P; Fidler, S; Frater, J; Fox, J
Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined. IVIG was well tolerated and no viral blips (> 50 HIV-1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: -3.7 log 10 copies/10 6 CD4 cells; controls: -3.87 log 10 copies/10 6 CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons. Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue. © 2017 British HIV Association.
Full Text Available BACKGROUND: Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. METHODS: We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. RESULTS: A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes. CONCLUSIONS: Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.
Parti, R; Mankarious, S
Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2-3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care-giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico-chemical tests (molecularsize distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non-specific binding of complement (anti-complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 degrees C. The reconstituted product was also found to be stable at room temperature (25 degrees C) up to 12 h.
Tang-Wai, Richard; Mailo, Janette; Rosenblatt, Bernard
Because immune mediated mechanisms are suspected in epileptogenesis, IVIg and corticosteroids have been used as alternatives to treat refractory seizures. We present our experience treating intractable epileptic children with IVIg and prednisone. Children with intractable epilepsy treated with prednisone or IVIg between 2005-2016 were reviewed retrospectively. Children with infantile spasms and autoimmune epilepsy were excluded. Data analyzed include epilepsy type and etiology, duration of epilepsy prior to treatment, seizure outcome, time to best seizure outcome, and adverse effects. Fifty-one patients were included: 26 received IVIg; 25 received prednisone. Etiologies were similar between cohorts: genetic (13 IVIg; 10 prednisone), lesional (8 IVIg; 7 prednisone), and unknown (5 IVIg; 8 prednisone). In the prednisone cohort, 92.0% had generalized epilepsy compared to 61.5% for IVIg. Among the IVIg treated, 84.6% responded (10 genetic, 4 unknown, and 8 lesional) with mean seizure reduction of 77.3% and mean time to best response of 9.8 weeks. With prednisone, 24.0% responded (2 genetic, 3 unknown, and 1 lesional) with a mean seizure reduction of 95.0% and mean time to best response of 2.7 weeks. Adverse effects occurred in 2 and 16 patients treated with IVIg and prednisone, respectively. The difference in responders and seizure reduction was statistically significant (p<0.0001 and p=0.001, respectively). IVIg had greater responders and lower adverse effects and honeymoon effect. This response was independent of epilepsy type, etiology, and duration suggesting different mechanisms of action between prednisone and IVIg and a common, reversible, immune-mediated pathway to intractability. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Conclusions: Nursing interventions of immunotherapy ensures the security of IVIG administration. Multidisciplinary cooperation promotes remission. Our findings can serve as reference for healthcare teams.
Ahmed, Alysia A.; Giddens, John; Pincetic, Andrew; Lomino, Joseph V.; Ravetch, Jeffrey V.; Wang, Lai-Xi; Bjorkman, Pamela J.
Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of Intravenous Immunoglobulin G (IVIG) requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of IVIG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal α2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully di-sialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro- to anti-inflammatory activity of the Fc. PMID:25036289
Markvardsen, L. H.; Sindrup, S. H.; Christiansen, I.
Background and purpose: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. Results: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...
Yoichi Kakuta, MD, PhD
Full Text Available Background. High-dose IVIG (2 g/kg alone or low-dose IVIG (100 mg/kg in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM to assess the effects of short-term super high-dose IVIG (4 g/kg administration with plasmapheresis before living-donor renal transplantation. Methods. Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4 after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4. The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen. Results. Upon completion (4 g/kg total or discontinuation of IVIG administration, 8 (47.1% of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions. Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4 within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.
De Dios, Jose Angelo A; Javaid, Adnan A; Ballesteros, Enrique; Metersky, Mark L
Granulomatous lymphocytic interstitial lung disease, or GLILD, is an uncommon condition associated with common variable immunodeficiency (CVID). We present an interesting case of an 18-year-old woman with Kabuki syndrome and CVID who was seen in our clinic for an abnormal chest CT scan. She was subsequently diagnosed with GLILD. There are no established guidelines for the treatment of GLILD in CVID. Immune globulin replacement therapy is the main treatment for CVID and higher doses of intravenous immunoglobulin (IVIG) may prevent the progression of chronic lung disease. Patients with CVID and GLILD are at increased risk for malignancy and their prognosis is worse compared to patients with CVID without GLILD.
Le Masson, Gwendal; Solé, Guilhem; Desnuelle, Claude; Delmont, Emilien; Gauthier-Darnis, Marc; Puget, Sophie; Durand-Zaleski, Isabelle
Prior clinical trials have suggested that home-based Ig treatment in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and its variant Lewis-Sumner syndrome (LSS) is safe and effective and is less costly than hospital-administered intravenous immunoglobulin (IVIg). A French prospective, dual-center, cost minimization analysis was carried out to evaluate IVIg administration (5% concentrated) at home versus in hospital with regard to costs, patients' autonomy, and patients' quality of life. The primary endpoint was the overall cost of treatment, and we adopted the perspective of the payer (French Social Health Insurance). Twenty-four patients aged 52.3 (12.2) years were analyzed: nine patients with MMN, eight with CIDP, and seven with LSS. IVIg (g/kg) dosage was 1.51 ± 0.43 in hospital and 1.52 ± 0.4 at home. Nine-month total costs per patient extrapolated to 1 year of treatment were €48,189 ± 26,105 versus €91,798 ± 51,125 in the home and hospital groups, respectively ( p home treatment were the good tolerance and absence of side effects of IVIg administration, as well as a good understanding of the advantages and drawbacks of home treatment (75% of respondents). The mRankin scores before and after switch to home treatment were 1.61 ± 0.72 and 1.36 ± 0.76, respectively ( p = .027). The switch from hospital-based to home-based IVIg treatment for patients with immune neuropathy represents potentially significant savings in the management of the disease.
Janjua, S.K.; Hussain, R.M.; Mohsin, S.T.; Iqbal, A.; Mishwani, A.H.
To evaluate the effects of intravenous immunoglobulin therapy on progression of severe sepsis in patients of poly trauma. Design: Quasi-experimental study. Place and Duration of Study: Combined Military Hospital Peshawar from June 2008 to Dec 2009. Patients and Methods: Forty six patients of poly trauma with severe sepsis were included. Along with the standard management i.e., surgical management, fluid resuscitation, antibiotics, analgesics, ionotropic, ventilatory and nutritional support, IVIG 5% (intravenous immunoglobulin) was infused over a period of 6 hours and repeated for three consecutive days. Sequential Organ Failure Assessment (SOFA) score was used to assess the progress in all the patients. Results: At the time of enrolment mean SOFA score was 5.41+- 1.127 and on the 15 day it was 1.62 +- 2.24, mean age was 39.21+10.26 years. Thirty four patients (73.91%) developed gram negative sepsis and eighteen patients (39.13%) developed septic shock. Mean duration of stay in ICU and on ventilatory support was 20.80+9.61 and 10.52 + 5.52 days respectively. Thirty five days mortality rate of these patients was 30.43%. Conclusion: The IVIG administration, when used along with the standard management appears to improve significantly the prognosis in patients of poly trauma with severe sepsis. (author)
procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc-receptor function, are subject to alterations during the preparation. The best preservation...... of such activity, when assessed in vitro, is obtained with polyethylene glycol precipitation or DEAE-Sephadex fractionation, whereas enzymatic or chemical treatment can potentially reduce the biologic activity. It is recommended that immunoglobulin preparations be evaluated in vitro for intact biologic function...
Mohammadzadeh, Iraj; Noei, Somayyeh; Babazadeh, Kazem; Zamani, Hassan; Barari-Savadkoohi, Rahim; Alizadeh-Navaei, Reza
Cardiac involvement was the major leading cause of death in patients with Kawasaki and IVIG administration reduces cardiac complications. The objective of this study was to determine the frequency of cardiovascular complications and duration of fever with regard to the time of intravenous immunoglobulin (IVIG) administration of patients with Kawasaki disease. This follow-up study was done on all patients with Kawasaki disease who were hospitalized at Amirkola Children's Hospital between 2006 and 2011. Diagnosis of Kawasaki was clinical and included fever more than 5 days with 4 of 5 signs containing mucosal changes, scaling and skin rash, bilateral nonexudative conjunctivitis, cervical lymph adenopathy and edema in lower extremities. After diagnosis of Kawasaki, all patients received standard treatment (intravenous immunoglobulins and aspirin) and undergoing cardiac echocardiography in 2 weeks, 2 months and 6 months. Information including age, sex, sign of diseases, laboratory findings, and cardiac complications in echocardiography were recorded. This study was performed on 100 patients (61 boys and 39 girls) with Kawasaki disease. The mean age of children was 2.8±2.6 years. Cardiac complication rate was 47% at the onset of the disease and had reached to 7% at the end of the sixth month (P=0.000). Distribution of cardiovascular complications in the second week, the second month and the sixth month after treatment was not significantly different according to the start of time of treatment (p>0.05). Duration of fever in patients who received treatment before 10 th day (1.5±1.3) did not have significant difference (P=0.78) with patients who received after 10 th day (1.6±0.9). Result shows that most of patients (99%) responded to the treatment with IVIG and ASA and cardiovascular complication ratio decreased. There was not significant relationship between duration of fever and time of IVIG treatment initiation.
van Klink, Jeanine M M; van Veen, Suzanne J; Smits-Wintjens, Vivianne E H J; Lindenburg, Irene T M; Rijken, Monique; Oepkes, Dick; Lopriore, Enrico
Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings. © 2015 S. Karger AG, Basel.
Full Text Available Dharshan Anandacoomaraswamy1, Jagdeesh Ullal2, Aaron I Vinik21Department of Internal Medicine, Coney Island Hospital, Brooklyn, NY, USA; 2Strelitz Diabetes Center, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAAbstract: This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia. Keywords: celiac disease, peripheral neuropathy, autoimmune disease, cerebellar ataxia, type 2 diabetes
Kovaleva, Lidia; Apte, Shashikant; Damodar, Sharat; Ramanan, Vijay; Loriya, Svetlana; Navarro-Puerto, Jordi; Khojasteh, Ali
To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma ® 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 9 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.
... molecules that are folded and shaped in three dimensions to fit over foreign materials or antigens such ... that are capa- ble of causing infections in man. There are a number of immune deficiency diseases ...
Full Text Available Abstract For patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.
Krivan, Gergely; Jolles, Stephen; Granados, Eduardo Lopes; Paolantonacci, Phillipe; Ouaja, Rabye; Cissé, Ousmane Alfa; Bernatowska, Ewa
Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient's life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient's compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient's preference and needs.
Oh, Eun-Jee; Jekarl, Dong Wook; Jang, Hyun-Sik; Park, Hae-Il; Park, Yeon-Joon; Choi, Hyun Ah; Chun, Chung-Sik; Kim, Yonggoo; Kim, Hyung Hoi
The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.
Paolantonacci, Philippe; Appourchaux, Philippe; Claudel, Béatrice; Ollivier, Monique; Dennett, Richard; Siret, Laurent
Polyvalent human normal immunoglobulins for intravenous use (IVIG), indicated for rare and often severe diseases, are complex plasma-derived protein preparations. A Quality by Design (QbD) approach has been used to develop the LFB new generation IVIG, targeting a high level of purity to generate an enhanced safety profile while maintaining a high level of efficacy. A modular approach of QbD was implemented consisting of five consecutive steps to cover all the stages from the product design to the final product control strategy. A well-defined target product profile was translated into 27 Product Quality Attributes (PQAs) that formed the basis of the process design. In parallel, a product risk analysis was conducted and identified 19 Critical Quality Attributes (CQAs) among PQAs. Process risk analysis was carried out to establish the links between process parameters and CQAs. Twelve critical steps were identified and for each of these steps a risk mitigation plan was established. Among the different process risk mitigation exercises, five process robustness studies were conducted at qualified small scale with a Design of Experiment (DoE) approach. For each process step, critical process parameters (CPPs) were identified and, for each CPP, Proven Acceptable Ranges (PARs) were established. The quality risk management (QRM) and risk mitigation outputs, including verification of PARs, were used to design the process verification exercise at industrial scale. Finally, the Control Strategy was established using a mix, or 'hybrid', of the 'traditional approach', plus elements of the QbD 'enhanced approach' as illustrated, to more robustly assign material and process controls, and in order to securely meet product specifications The advantages of this QbD approach were improved process knowledge for industrial design and process validation and a clear justification of the process and product specifications as a basis for control strategy and future comparability exercises
Roed, H.G; Langkilde, Annika Reynberg; Sellebjerg, F
OBJECTIVE: To investigate if IV immunoglobulin (IVIG) treatment in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. METHODS: Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty...... during follow-up. CONCLUSIONS: There was no effect of IV immunoglobulin (IVIG) on long-term visual function following acute optic neuritis, nor was there an effect of IVIG treatment in reducing latency on visual evoked potentials and thus preserving function of axons of the optic nerve...
Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji
Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.
Brand, A.; Vuist, W. M.; van Schaik, I. N.; Vermeulen, M.
High doses of immunoglobulins (IVIG) may have beneficial effects in patients with autoimmune diseases. In this review several different mechanisms of action are discussed. These mechanisms include effects on the effector phase of the immune response, on the initial steps of the immune response and
Relkin, Norman R; Thomas, Ronald G; Rissman, Robert A; Brewer, James B; Rafii, Michael S; van Dyck, Christopher H; Jack, Clifford R; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M; Fritsch, Sandor; Aisen, Paul S
We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. NCT00818662. This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD. © 2017 American Academy of Neurology.
Crighton, Gemma L; Scarborough, Ri; McQuilten, Zoe K; Phillips, Louise E; Savoia, Helen F; Williams, Bronwyn; Holdsworth, Rhonda; Henry, Amanda; Wood, Erica M; Cole, Stephen A
To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry. Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected. This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial.
Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael
Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.
Nyborg, Kathinka Marie; Kolte, Astrid Marie; Larsen, Elisabeth Clare
. SETTING: Tertiary care university hospital. PATIENT(S): Fifty-two patients with a history of at least three consecutive pregnancy losses after ART who underwent at least one further ART cycle with concurrent immunomodulation in 2003-2012. INTERVENTION(S): Immunomodulation with IV immunoglobulin......OBJECTIVE: To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm injection assisted reproductive technology (ART) cycles where immunomodulation was given to patients with recurrent pregnancy loss after prior ART treatments. DESIGN: Retrospective cohort study...
Honjo, T; Alt, F. W; Rabbitts, T. H
... Cataloguing in Publication Data Immunoglobulin genes 1. Vertebrates. Immunoglobulins 1. Honjo, T. II. Alt, F.W. III. Rabbitts, T.H. 612'. 118223 ISBN 0-12-354865-9 This book is printed on acid-free paper ( T...
Alhossain A. Khalafallah
Full Text Available There are few data available regarding the prevalence of infection in multiple myeloma (MM patients in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide or post autologous stem cell transplantation. We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequently to thalidomide, because of disease progression and 22 patients underwent autologous stem cell transplantation. The median age was 64 years (range 37-86, with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe infections. All patients except 3 received intravenous immunoglobulin (IVIG therapy with a significant decline of the rate of infection thereafter. Our analysis shows that IVIG appears to be an effective strategy to prevent infection in MM patients. Further studies to confirm these findings are warranted.
RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations.
Wasserman, Richard L; Greener, Benjamin N; Mond, James
Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects. Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients. Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD). This product offers potential advantages over other available IG's for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition. In addition to its enhanced neutralizing anti-RSV activity and its polyclonal IG composition, there is preclinical data to support the use of RI-002 for humoral protection against other respiratory pathogens.
Roed, H.G; Langkilde, Annika Reynberg; Sellebjerg, F
OBJECTIVE: To investigate if IV immunoglobulin (IVIG) treatment in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. METHODS: Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty-fo...
Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study.
Boada, M; Ramos-Fernández, E; Guivernau, B; Muñoz, F J; Costa, M; Ortiz, A M; Jorquera, J I; Núñez, L; Torres, M; Páez, A
There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(®) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(®) with intravenous immunoglobulin replacement (Flebogamma(®) DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. the AMBAR study represents a new therapeutic perspective for AD. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Full Text Available CANOMAD is a rare chronic neuropathy, characterized by chronic sensory ataxia and intermittent brain stem symptoms due to antidisialosyl antibodies. The disorder results in significant morbidity but is poorly understood and often misdiagnosed. We describe a unique case of CANOMAD, associated with involuntary movements of the face; patient reported exacerbations with citrus and chocolate and respiratory muscle weakness. Our patient was initially misdiagnosed with Miller Fisher Syndrome, highlighting the need for vigilance should neurological symptoms recur in patients initially diagnosed with a Guillain Barre variant. Moreover, the optimal treatment is unknown. This patient responded remarkably to intravenous immunoglobulin and has been maintained on this treatment, without further exacerbations.
Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J
The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients. © The Author(s) 2016.
Full Text Available Primary antibody deficiency (common variable immunodeficiency, Hyper IgM, X-linked agammaglobulinemia and selective Ig A deficiency is a group of heterogeneous diseases characterized by defective antibody production. In primary hypogammaglobulinemias, particularly in patients with common variable immunodeficiency there is an increased generation of reactive oxygen species from monocytes which may be important for both immunopathogenesis and clinical manifestations. The generation of toxic oxygen metabolites may contribute to inflammation and tissue damage associated with phagocytic infiltration, and play role in the pathogenesis of malignancies, autoimmune disorders, acute and chronic pulmonary diseases seen in these patients. In primary immunodeficiencies and functional antibody deficiencies, IVIG act as replacement therapy and several mechanisms of IVIG action have been postulated. In vitro studies with human granulocytes showed stimulation of respiratory burst and promotion of bacterial killing by IVIG. In adult patients with primary humoral immunodeficiency, treated with IVIG showed that IVIG does not affect superoxide generation. We investigated superoxide generation from PMNL in 35 children with hyper IgM syndrome, XLA, CVID and IgA deficiency and 13 healthy children. We also explored the effect of IVIG administration on superoxide generation from granulocytes, white cell count, absolute neutrophil count, absolute lymphocyte count and quantitative CRP levels. There was a substantial increase in superoxide generation from PMNL in patients with XLA, CVID and IgA deficiency. Comparison of the superoxide generation before, 24 hours and one week after IVIG treatment showed no difference. In patients with CVID, quantitative CRP levels before and 24 hours after IVIG revealed significant difference. Other parameters were not changed. It can be concluded that enhanced superoxide generation in patients with XLA, CVID, Ig A deficiency may result from
of ventilation therapy and time to clinical recovery. There were no significant differences in the treated and ... shown in vitro in neonatal animals.3 When this study commenced in 1987, the majority of patients ..... and M. Pather, who assisted us with the clinical investigations. REFERENCES. 1 Chmco G. Rondinl G. O,ebani A.
Michael T. Flannery
Full Text Available IVIg therapy has potentially been related to arterial and venous therapy. We performed an Ovid review focusing on IVIg and thrombotic events. While a few case reports were reviewed case series and case control studies were particularly reviewed in relation to thrombotic events. Outcomes demonstrate a correlation between underlying cardiovascular risk factors with predominately arterial events which typically occurred within 4–24 hours of infusion. While venous events occurred less commonly they were associated with traditional risk factors and occurred later, typically, 1–7 days following infusion of IVIg. Potential causation of thrombotic events was discussed.
Pleass, Richard J; Moore, Shona C; Stevenson, Liz
Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with whic...
Kearns, Sean; Kristofek, Loretta; Bolgar, William; Seidu, Luqman; Kile, Samantha
Patients with primary immune deficiency (PID) often require immunoglobulin G (IgG, commonly referred to as Ig) replacement therapy to prevent infections and associated comorbidities. Ig therapy can be given either through intravenous or subcutaneous routes, and both can be done in the home setting. There is limited information available on the real-world diagnosis, management, and outcomes of this patient population, given the variable disease presentation and treatment options. The Immunoglobulin Diagnosis, Evaluation, and key Learnings (IDEaL) Patient Registry is designed to capture nursing, pharmacy, and patient-reported data for patients receiving Ig at home. To (a) present a real-world population of patients with PID who have received Ig at home and (b) examine how differences in administration, dosing, and insurance affect health and quality-of-life outcomes in these patients. As of July 2015, 383 patients receiving Ig therapy from Coram/CVS specialty infusion services, across multiple disease states, signed consent forms and enrolled in the IDEaL Patient Registry. Patients' referral paperwork, including lab values, and standard of care nursing and pharmacy follow-up forms were collected. Patients were mailed quality-of-life surveys at the time of enrollment and every 6 months after their enrollment. The most common diagnosis (78%) in these PID patients was common variable immunodeficiency (CVID). For Ig-naive adult patients, the average age at the start of treatment was 59 years. For pediatric patients, average age at start of treatment was 9 years. A majority of these PID patients (80%) received subcutaneous Ig (SCIg) at home, and 20% received intravenous Ig (IVIg). The average SCIg dose was 10 grams per week, or 130 mg per kg, and the average IVIg dose was 36 grams every 4 weeks, or 472 mg per kg. In the IVIg patient population, 34% had a dose or frequency change while on treatment, while 30% of the SCIg patients had a dose or frequency change. Patient
P. KARIMZADEH MD; M. GHOFRANI MD
Objective:Acute inflammatory demyelinating peripheral neuropathy (Guillain-Barre-Syndrome) is by far the most common cause of immune-medicated peripheral nervous system disease in children; with the near disappearance of poliomyelitis, GBS is responsible for the great majority of cases of acute flaccid paralysis. So far, in several controlled studies, corticosteroids, plasmapheresis and IVIG have been utilized in pediatric patients, afflicted with GBS. Regarding IVIG therapy, two methods have...
Sriaroon, Panida; Ballow, Mark
Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available
There are few data available regarding the prevalence of infection in multiple myeloma (MM patients in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide or post autologous stem cell transplantation. We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequently to thalidomide, because of disease progression and 22 patients underwent autologous stem cell transplantation. The median age was 64 years (range 37-86, with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe infections. All patients except 3 received intravenous immunoglobulin (IVIG therapy with a significant decline of the rate of infection thereafter. Our analysis shows that IVIG appears to be an effective strategy to prevent infection in MM patients. Further studies to confirm these findings are warranted.
Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert
and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...
Massoud, Amir H; Kaufman, Gabriel N; Xue, Di; Béland, Marianne; Dembele, Marieme; Piccirillo, Ciriaco A; Mourad, Walid; Mazer, Bruce D
IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 + regulatory T cells (Treg). Using mice carrying a DTR/EGFP transgene under the control of the Foxp3 promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags. Copyright © 2017 by The American Association of Immunologists, Inc.
Lee, D C; Lederman, H M
The levels of anti-tetanus toxoid IgG antibodies were measured in 29 lots of intravenous gamma globulin (IVIG). The antibody levels varied from 4 to 90 IU/mL (geometric mean, 18.6; 90% confidence interval, 9.7-35.7). The variation from manufacturer to manufacturer accounted for most of the observed differences among lots; there was relatively little variability among multiple lots from a single manufacturer. IVIG may be an acceptable alternative to horse or human tetanus immune globulin.
Full Text Available Abstract Background Hereditary Inclusion Body Myopathy (HIBM is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM, has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG, in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22% directly after IVIG loading to 25.6 kg (+35% at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44% directly after IVIG loading to 6.0 kg (+46% at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.
Full Text Available Objective: Acute inflammatory demyelinating peripheral neuropathy (Guillain-Barre-Syndrome is by far the most common cause of immune–mediated peripheral nerve disease in children and with the near disappearance of poliomyelitis, is responsible for the great majority of cases of acute flaccid paralysis. Several controlled studies have done with corticosteroids, plasma pheresis and IVIG in pediatric patients. IVIG treatment can be done in two types of treatment: 1- High dose that means 1gr/kg/day for 2 days. 2- Low dose that means 400mg/kg/day for 5 days. Several studies in other countries have shown faster rate of recovery in patients who received total dose of IVIG in 2 days as opposed to 5 days. Materials & Methods: Because we have not any study about this two types of treatment in IRAN we decided to comparison this two types of IVIG treatment. So the patients that referred to Mofid children hospital for weakness and we diagnosed GBS (with history, physical examination, laboratories and EMG-NCV are divided in two groups: 1- High dose IVIG treatment (experimental group. 2- Low dose IVIG treatment (control group Then the results evaluated. Results: Our findings included that in high dose IVIG therapy we have faster rate of recovery and the Hospital stay is shorter than low dose IVIG-therapy. Also in this type of treatment “because the patients cure faster” , so complications are decreased in them. In the group of high dose IVIG therapy, lower and upper extremities weakness decreased in time. Conclusion: We did not receive any relationship between side effects of drugs and the type of treatment. The relationship between high dose IVIG therapy and drug side effects was not significant.
Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; de Moraes-Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares
We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG) therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection.
Wasserman, Richard L
Immunoglobulin therapy is a key element in the management of most patients with primary immunodeficiency disease. Allergist/immunologists should be familiar with the appropriate evaluation of candidates for immunoglobulin, the characteristics of immunoglobulin products, and how to use them to provide the best care to their patients. Available immunoglobulin products appear to be equally efficacious, but they are not interchangeable. Minimizing the risk of serious adverse events and controlling minor side effects is important to ideal patient care. Immunoglobulin may be administered intravenously or subcutaneously. Individualizing the choice of immunoglobulin product, mode of administration, and site of care can optimize the clinical outcome and minimize the burden of care. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Batard, T; Zimmer, A; Nony, E; Bouley, J; Airouche, S; Luce, S; Turfkruyer, M; Tourdot, S; Mascarell, L; Moingeon, P
Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation. BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively. AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2, Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells. In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma
Sellebjerg, Finn Thorup
The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...
Hemostasis was well achieved. The tumor weighed 6.7 kg. The postoperative course. Intravenous Leiomyomatosis. Narayanaswamy Mariyappa, Uday Kumar Manikyam1, Dinesh Krishnamurthy2, Preeti K,. Yamini Agarwal, Prakar U. Departments of Obstetrics and Gynaecology, 1Pathology and 2Anaesthesia, Sri Devaraj ...
Smit, A. A.; Vermeulen, M.; Koelman, J. H.; Wieling, W.
A 33-year-old woman with acute idiopathic postganglionic panautonomic neuropathy experienced prompt recovery of all dysautonomic symptoms after receiving high-dose intravenous immunoglobulin therapy. Her recovery was complete within 6 months after onset of disease. This unusually rapid and complete
Perez, Elena E; Orange, Jordan S; Bonilla, Francisco; Chinen, Javier; Chinn, Ivan K; Dorsey, Morna; El-Gamal, Yehia; Harville, Terry O; Hossny, Elham; Mazer, Bruce; Nelson, Robert; Secord, Elizabeth; Jordan, Stanley C; Stiehm, E Richard; Vo, Ashley A; Ballow, Mark
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Elalfy, Mohsen Saleh; Elbarbary, Nancy Samir; Abaza, Heba Wegdan
Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion.
Full Text Available Background: The most common cause for acute onset of thrombocytopenia in an otherwise well child is (autoimmune idiopathic thrombocytopenic purpura (ITP. The incidence of ITP appears to be greater in children than in adult. The incidence of ITP in children is estimated to be approximately 46 new cases per million population per year. Prednisolone, typically given as a single dose of 1-4 mg/kg/day, is indicated for all patients with symptomatic thrombocytopenic purpura and probably for all patients with platelet counts below 30000-50000/μL who may be at increased risk for hemorrhagic complication. An alternative to corticosteroid therapy for ITP is IVIG, but is much more expensive, has significant side effects, and is not significantly superior to steroid therapy to justify the expense and side effects of its use. In acute ITP, 80% of patients respond initially, with more rapid increase in platelet counts compared to steroid treatment. To the best of our knowledge, this is the first study in Iran comparing the efficacy of prednisolone and IVIG in the treatment of ITP.Methods: In this retrospective study, 202 ITP patients were treated with either prednisolone or IVIG between 1995 and 2005 at the Childrens' Medical Center, Tehran, Iran. We compared the efficacy of prednisolone and IVIG in increasing the platelet counts of ITP patients. In addition, we collected the following patient data: seasonal incidence, age distribution, gender, parental consanguinity, and platelet count on admission.Results: There were no meaningful differences between IVIG and prednisolone in the treatment of ITP (z test with p<0.05. ITP was more common in males, with the highest incidence in the age range of 2-8 years old.Conclusion: Because there was no statistical difference between the outcome of the IVIG and prednisolone treatments, we recommend that prednisolone be the drug of choice to treat ITP.
O. G. Kimirilova
Full Text Available The authors give the material of their own observations on the clinical and laboratory efficacy of the Russian intravenous immunoglobulin Gabriglobin for the treatment of enteroviral meningitides in children.The performed trials indicated that the use of Gabriglobin in the combination therapy of severe enteroviral meningitides in children reduced the duration of intoxication, global cerebral symptoms, meningeal syndrome, the time of cerebrospinal fluid sanitation by 1,5 times, and that of in-hospital treatment by 5,8±1,8 days as compared to those who received conventional basic therapy.
Diaz, Marilyn; Casali, Paolo
Immunoglobulin hypermutation provides the structural correlate for the affinity maturation of the antibody response. Characteristic modalities of this mechanism include a preponderance of point-mutations with prevalence of transitions over transversions, and the mutational hotspot RGYW sequence. Recent evidence suggests a mechanism whereby DNA-breaks induce error-prone DNA synthesis in immunoglobulin V(D)J regions by error-prone DNA polymerases. The nature of the targeting mechanism and the t...
Walther, Stefanie; Rusitzka, Tamara V; Diesterbeck, Ulrike S; Czerny, Claus-Peter
Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo
Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders. Copyright© Ferrata Storti Foundation.
European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision
van den Bergh, Peter Y. K.; Hadden, Robert D. M.; Bouche, Pierre; Cornblath, David R.; Hahn, Angelika; Illa, Isabel; Koski, Carol L.; Leger, Jean-Marc; Nobile-Orazio, Eduardo; Pollard, John; Sommer, Claudia; van Doorn, Pieter A.; van Schaik, Ivo N.
Recommendations: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg)
... intravenous immunoglobulin (IVIG) or removal of the spleen (splenectomy) may be considered. You may receive treatment to ... need special treatment. In most people, steroids or splenectomy can totally or partially control anemia.
Full Text Available an autoimmune disease, the most common treatment is the administration of oral steroids to inhibit antibody...pressants, plasma exchange, and the administration of high-dose intravenous immunoglobulin (IVIG). Skin and
Djoumerska-Alexieva, Iglika; Manoylov, Iliyan; Dimitrov, Jordan D; Tchorbanov, Andrey
B cells producing IgG antibodies specific to a variety of self- or foreign antigens are a normal constituent of the immune system of all healthy individuals. These naturally occurring IgG antibodies are found in the serum, external secretions, and pooled human immunoglobulin preparations. They bind with low affinity to antigens, which can also be targets for pathologic autoantibodies. An enhancement of naturally occurring IgG autoantibody activity was observed after treatment of human IgG molecules with protein-destabilizing agents. We have investigated the interactions of human immunoglobulins that were obtained from serum or from breast milk of healthy individuals or IVIg with human liver antigens. Proteins from an individual serum or milk were isolated by two methods, one of which included exposure to low pH and the other did not. Purified serum, mucosal IgM, IgA, and the fraction containing immunoglobulin G F(ab')2 fragments each inhibited the binding of a single donor or pooled IgG to human liver antigens. Our study presents findings regarding the role of the breast milk or serum antibodies in blocking the self-reactivity of IgG antibodies. It supports the suggestion that not IVIg only, but also the pooled human IgM and IgA might possess a potent beneficial immunomodulatory activity in autoimmune patients. © 2013 APMIS. Published by John Wiley & Sons Ltd.
Kundak, Selcen; Bağ, Özlem; Gülez, Nesrin; Ergin, Malik
Subcorneal pustular dermatosis (SPD) is a rare, chronic, recurrent dermatosis characterised by sterile pustules. It develops mainly in middle-aged or elder women, but is also rarely seen in children. The exact aetiology of the disease is unknown. In literature, cases associated with IgA gammopathy have been reported. In this article; we report a case of a five-year-old girl who was diagnosed as SPD by clinical features, histopathological characteristics, and direct immunofluorescence analysis results. IgA was high, and IgG-IgM and CD19+ B cell were low. We noticed that during IVIG treatment for immunodeficiency, dermatological symptoms were recovered rapidly. Clinical profile of SPD and its association with systemic diseases may provide early detection of immune dysfunction.
Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 1 (2014) >. Log in or Register to get access to full text downloads.
Jønch, Aia E; Danielsen, Else R; Thomsen, Carsten
ABSTRACT: BACKGROUND: Adrenomyeloneuropathy (AMN) is one of several phenotypes of the adrenoleukodystrophy spectrum caused by mutations in the ABCD1 gene on the X chromosome. An inflammatory component is part of the disease complex ranging from severe childhood CNS demyelination to spinal cord...
Brocklehurst, Peter; Farrell, Barbara; King, Andrew
Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...... suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality....
Brocklehurst, Peter; Farrell, Barbara; King, Andrew
Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...
Kobayashi, Tohru; Saji, Tsutomu; Otani, Tetsuya; Takeuchi, Kazuo; Nakamura, Tetsuya; Arakawa, Hirokazu; Kato, Taichi; Hara, Toshiro; Hamaoka, Kenji; Ogawa, Shunichi; Miura, Masaru; Nomura, Yuichi; Fuse, Shigeto; Ichida, Fukiko; Seki, Mitsuru; Fukazawa, Ryuji; Ogawa, Chitose; Furuno, Kenji; Tokunaga, Hirohide; Takatsuki, Shinichi; Hara, Shinya; Morikawa, Akihiro
Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, pKawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted. Japanese Ministry of Health, Labour and Welfare. Copyright © 2012 Elsevier Ltd. All rights reserved.
The effects of adjuvant immunoglobulin M-enriched immunoglobulin therapy on mortality rate and renal function in sepsis-induced multiple organ dysfunction syndrome: retrospective analysis of intensive care unit patients.
Yavuz, L; Aynali, G; Aynali, A; Alaca, A; Kutuk, S; Ceylan, B G
To determine the effect of immunoglobulin (Ig)M-enriched Ig therapy on mortality rate and renal function in sepsis-induced multiple organ dysfunction syndrome (MODS), using the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Retrospective study of patients with sepsis-induced MODS treated with standard antibiotic plus supportive therapy (control group) or IgM-enriched Ig therapy adjuvant to control group therapy (IVIg group). Total length of stay in the intensive care unit (ICU), overall mortality rate and 28-day case fatality rate (CFR), as well as APACHE II scores and renal function parameters at day 1 and day 4 of therapy, were recorded. A total of 118 patients were included (control group, n = 62; IVIg group, n = 56). In both groups, day 4 APACHE II scores decreased significantly compared with day 1 scores; the effect of treatment on renal function was minimal. Length of ICU stay, overall mortality rate and 28-day CFR were significantly lower in the IVIg group compared with the control group. Adding IgM-enriched Ig therapy to standard therapy for MODS improved general clinical conditions and significantly reduced APACHE II scores, overall mortality rate and 28-day CFR, although effects on renal function were minimal.
Young, Megan K; Bertolini, Joseph; Kotharu, Pushpa; Maher, Darryl; Cripps, Allan W
Rubella antibodies are not routinely measured in immunoglobulin products and there is a lack of information on the titer in Australian products. To facilitate future studies of the effectiveness of passive immunisation for preventing rubella and congenital rubella syndrome, this study measured the concentration of rubella-specific antibodies in Australian intramuscular (IM) and intravenous (IV) human immunoglobulin products suitable for post-exposure prophylaxis using a chemiluminescent immunoassay. The GMT ± GSD for the IM product was 19 ± 1.2 IU/mg (2980 ± 1.2 IU/mL). The GMT ± GSD for the IV product was 12 ± 1.5 IU/mg (729 ± 1.5 IU/mL). At present, Australian guidelines recommend offering non-immune pregnant women exposed to rubella 20 mL of intramuscular immunoglobulin within 72 hours of exposure. This equates to 42,160 IU of rubella antibodies if the lowest titer obtained for the Australian IM product is considered. The same dose would be delivered by 176 mL of the Australian IV product at the lowest measured rubella-specific antibody titer.
Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong
Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....
The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...
Fernanda Aimée NOBRE
Full Text Available SUMMARY We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection.
Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report.
Ajmi, Houda; Mabrouk, Sameh; Hassayoun, Saida; Regaieg, Haifa; Tfifha, Minyar; Jalel, Chemli; Skouri, Hadef; Zouari, Noura; Abroug, Saoussan
Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.
Full Text Available Cynthia A Mundy, Jatinder Bhatia Department of Pediatrics, Division of Neonatology, Georgia Regents University, Children's Hospital of Georgia, GA, USA Abstract: Hemolytic disease of the newborn continues to be a common neonatal disorder that requires a comprehensive understanding on the part of those caring for infants. Common treatments include hydration and phototherapy. Exchange transfusion is used in severe hemolytic disease, but infants undergoing this treatment are exposed to many adverse effects. Intravenous immunoglobulin is a newer strategy that is showing promise in the treatment of the disease. This review discusses the current use and future expectations of intravenous immunoglobulin therapy in newborns. Keywords: hyperbilirubinemia, ABO incompatibility, neonatal jaundice
Marie, I; Chérin, P; Michallet, M; Pelus, E; Dantal, J; Crave, J-C; Delain, J-C; Viallard, J-F
Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Binek, Alicja; Jarosz-Chobot, Przemysława
Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.
Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco
The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.
Reglinski, Mark; Lynskey, Nicola N; Choi, Yoon Jung; Edwards, Robert J; Sriskandan, Shiranee
Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Welling, M. (Dept. of Diagnostic Radiology and Nuclear Medicine, University Hospital, Leiden (Netherlands)); Feitsma, H.I.J. (Dept. of Diagnostic Radiology and Nuclear Medicine, University Hospital, Leiden (Netherlands)); Calame, W. (Dept. of Diagnostic Radiology and Nuclear Medicine, University Hospital, Leiden (Netherlands)); Ensing, G.J. (Mallinckrodt Medical, Petten (Netherlands)); Goedemans, W. (Mallinckrodt Medical, Petten (Netherlands)); Pauwels, E.K.J. (Dept. of Diagnostic Radiology and Nuclear Medicine, University Hospital, Leiden (Netherlands))
To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P<0.03) higher for the purified than for the unpurified immunoglobulin. For the in vivo study, mice were infected in the thigh muscle with Staph. aureus or K. pneumoniae. After 18 h 0.1 mg of technetium-99m labelled polyclonal immunoglobulin or [sup 99m]Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P<0.03) for protein charge-purified polyclonal immunoglobulin than for unpurified polyclonal human immunoglobulin. Already within 1 h the infected tissues could be detected by the purified immunoglobulin. It is concluded that [sup 99m]Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than [sup 99m]Tc-labelled unpurified immunoglobulin. (orig.)
Goncharova, Kateryna; Lozinska, Liudmyla; Arevalo Sureda, Ester; Woliński, Jarosław; Weström, Björn; Pierzynowski, Stefan
Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer) has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent) were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins) and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.
Full Text Available Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.
Lozinska, Liudmyla; Arevalo Sureda, Ester; Woliński, Jarosław; Weström, Björn; Pierzynowski, Stefan
Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer) has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent) were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins) and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels. PMID:28658291
In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness. However ...
Revol, Bruno; Bickert, Laura; Sarrot-Reynauld, Françoise; Allenet, Benoit
Patients have to be informed about the risks and benefits of medicinal products derived from human plasma. No study has examined the patient's perspective yet. Our objective was to assess perceived benefits and risks of immunoglobulins administration from the patient's point of view. Thirty-four patients receiving subcutaneous or intravenous immunoglobulins for chronic disorders at a single university hospital were asked to complete a survey. Although the level of comfort was high, the results revealed variable and incomplete knowledge, in particular about the nature of the treatment. Greater efforts should be made by health professionals to provide information to patients about plasma-derived medicinal products. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.
Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl
. Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. CONCLUSION: This study...... have beneficial effects. However, IVIG may also have adverse effects. With this trial we will estimate the effects of IVIG on a patient-reported outcome and other patient-centred outcomes in patients with NSTI. METHODS: INSTINCT is a randomised, double-blinded, parallel-group, placebo-controlled trial...
Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz
accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid...... and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin....... The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins...
The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE. Copyright © 2016 Elsevier B.V. All rights reserved.
Marcia Cristina Zago Novaretti
Full Text Available Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia, Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.
Benchekroun, Laila; Ouzzif, Zohra; Bouabdillah, Mounya; Jaouhar, Nouzha; Aoufir, Fatiha; Aoufi, Farida; Chabraoui, Layachi
The immunoglobulin D multiple myeloma is a rare form of multiple myeloma and affects a young population. It is characterized by its clinical severity and poor prognosis. We report four cases of multiple myeloma immunoglobulin D diagnosed and supported in the university hospital Center of Sale and Rabat-Morocco. We propose to study the epidemiological, clinical and biological characteristics of this rare type of monoclonal gammopathy. Through the observations reported, the clinical aspect of myeloma is characterized by the high frequency of extra-bone manifestations including impaired kidney function. The immunoglobulin D multiple myeloma is mainly type λ, the IgD κ is rare, the predominance of λ light chains could be explained by rearrangements at the immunoglobulin genes. Bence-Jones proteinuria is almost constant in the multiple myeloma immunoglobulin D, it is mainly type λ, reflecting excess production of light chains by plasma cells. The marrow is invaded by plasma cells in very different proportions of up to 95%. It's a clinical entity, difficult to diagnose, particularly when low homogeneous band on electrophoresis goes unnoticed for an eye inexperienced or when immune serum anti-IgD was not used during the immunotyping.
Schneider, Lutz; Dieckmann, Ralf; Hackert, Thilo; Gebhard, Martha-Maria; Werner, Jens
Five percent of alcoholics develop an acute pancreatitis (AP). The mechanism leading to pancreatic injury is not yet understood. Microcirculatory disorders seem to play a pivotal role. The objective of this study was to compare alcoholic pancreatic injury in response to intravenous and intragastric routes of alcohol administration. Alcohol was applied in rats intravenously (IV) or gastric via a surgical implanted feeding tube (IG). Serum alcohol concentration was maintained between 1.5‰ and 2.5‰. Four subgroups (n = 6/group) were examined in the IV/IG arm and compared with healthy controls. Pancreatic microcirculation, enzyme levels, and morphological damage were assessed after 3, 6, 12, and 24 hours. Microcirculatory analysis showed significantly disturbed pancreatic perfusion and increased adherent leukocytes in IV and IG animals. In IV and IG groups, serum amylase was increased without morphological signs of AP compared with healthy controls. Alcohol application does not induce AP in rodents, but impairs pancreatic microcirculation irrespectively of the application route. Intravenous application is commonly used and shows no disadvantages compared with the physiological intragastric application form. Therefore, the intravenous route offers a valid model, which mimics the physiological process for further studies of the influence of acute alcohol intoxication on the pancreas.
Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J
The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Welling, M.; Feitsma, H.I.J.; Calame, W.; Ensing, G.J.; Goedemans, W.; Pauwels, E.K.J.
To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P 99m Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P 99m Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99m Tc-labelled unpurified immunoglobulin. (orig.)
Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano
Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.
Morteza Talebi Doluee
Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.
Pitarokoili, Kalliopi; Kohle, Felix; Motte, Jeremias; Fatoba, Oluwaseun; Pedreiturria, Xiomara; Gold, Ralf; Yoon, Min-Suk
Intravenous human immunoglobulins dominate in the treatment of autoimmune neuropathies. We introduce intrathecal application as a new option for experimental autoimmune neuritis in Lewis rats. After immunisation with neuritogenic P2 peptide, we show a therapeutic and preventive effect of intrathecal human immunoglobulins (5-40mg/kg) on clinical and electrophysiological neuritis signs. Histology corroborated a lower degree of inflammation, demyelination, ICAM-1-dependent blood-nerve-barrier permeability and complement activation in the sciatic nerve. After preventive application, immunoglobulins induced a Th2 cytokine shift in the peripheral nerves already before clinical neuritis signs. Intrathecal immunoglobulin application could be a novel immunomodulatory option for autoimmune neuropathies. Copyright © 2017 Elsevier B.V. All rights reserved.
Rajabally, Yusuf A
Intravenous immunoglobulin therapy is of proven effect in chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In more recent years, there have been a number of anecdotal case reports and small series, followed by a few trials of variable design, of subcutaneous immunoglobulin therapy in these neuropathies. To date, limited evidence suggests that the subcutaneous route may be a more clinically effective, better-tolerated, at least cost-equivalent and a more patient-friendly option than the still more used intravenous alternative. Long-term efficacy is not as yet established in neuropathic indications by randomised controlled clinical trial evidence, and it is likely that the subcutaneous route may not be suitable in all cases with some hints to this effect appearing from the limited data available to date. Further studies are ongoing, including those of dose comparison, and more are likely to be planned in future. The literature on the use of subcutaneous immunoglobulin therapy in chronic inflammatory neuropathy is reviewed here. The current use in clinical practice, day-to-day benefits, including quality of life measures and health economics as published thus far, are evaluated. The limitations of this form of treatment in CIDP and MMN are also analysed in the light of current literature and taking into account the remaining unknowns. Future prospects and research with this mode of immunoglobulin therapy administration are discussed.
Hoan, Nhung Tran Khai; Karmochkine, M; Laccourreye, O; Bonfils, P
To study the effect of the introduction of a substitution by intravenous Immunoglobulins (Ig IV) at patients with immunoglobulins G (IgG) subclasses deficiency and nasal polyposis. Prospective study concerning five patients with IgG subclasses deficiency and nasal polyposis treated by Ig IV. Rhinologic, otologic and pulmonary symptoms, exacerbations of nasal polyposis, chronic otitis and asthma as well as the number of antibiotics and corticoids treatments were counted during the Ig IV substitution. To study the association between IgIV substitution and the number of exacerbations of nasal polyposis, chronic otitis, asthma and the number of antibiotics and corticoids treatments in patients with IgG subclasses deficiency and nasal polyposis. Five patients with a IgG subclass deficiency and nasal polyposis were substituted. The number of antibiotics and corticoids cures increased at one patient and remained stable at four others. The number of sinus, ear and lung infections as well as the global rhinologic score of symptoms and the endoscopic stage of the nasal polyposis remained stable. In the absence of efficiency of the treatment, this one was interrupted at the end of 6 months for patients n° 1 and n° 3, 24 months for patient n° 4 and 42 months for patient n° 5. The current study failed to highlight clinical improvement in patients wih IgG subclasses deficiency and nasal polyposis treated by Ig IV. A previous study had not allowed to find a link between IgG subclasses deficiency and severity of nasal polyposis, what seems to be confirmed by the absence of improvement brought during the substitution of this deficit in the current study.
Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman
To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. © 2016 Société Française de Pharmacologie et de Thérapeutique.
Adam, Zdeněk; Szturz, Petr; Krejčí, Marta; Vašků, Vladimír; Pour, Luděk; Michalková, Eva; Ševčíková, Sabina; Čermáková, Zdeňka; Veselý, Karel; Vaníček, Jíří; Pourová, Eva; Král, Zdeněk; Mayer, Jiří
The mucinoses of the type of scleredema and scleromyxedema are diseases marked by excessive production of mucin deposits in the skin and subcutaneous tissue, which causes skin hardening. The skin and subcutaneous deposits hamper the movement of limbs, the thorax as well as mouth. The same mechanism also damages other organs (the heart, lungs, oesophagus). It is probably caused by the stimulation of mucin production in fibroblasts by immunoglobulins, frequently monoclonal immunoglobulin. Therefore these diseases are typically associated with monoclonal gammopathy. We describe a cohort of 4 patients, skin manifestations were twice identified as scleredema and twice as scleromyxedema. All the four patients had type IgG monoclonal immunoglobulin and had clonal plasma cells in the bone marrow proven by histologic examination and flow cytometry. Therefore we commenced chemotherapy in all of them. In one case this chemotherapy was ended by a high-dose chemotherapy with transplanting of autologous red blood cells. This therapy attained the complete disappearance of monoclonal immunoglobulin as well as cutaneous and extracutaneous manifestations of scleredema (obstipation). In one case chemotherapy led to partial hematologic remission and partial improvement of skin manifestations. The other two patients did not respond to standard chemotherapy. The condition of one of them resulted in dermato-neuro syndrome (confusion, somnolence passing into coma and grand mal seizure) and improved following an intensive treatment including also intravenous application of immunoglobulins in a dose of 2 g/per 1 kg weight. This patient has now been under long-term treatment with these immunoglobulins, during which the skin symptoms have significantly diminished, but the concentration of monoclonal immunoglobulin has not changed. The fourth patient not responding to standard chemotherapy was treated with intravenous immunoglobulins also in a dose of 2 g/per 1 kg of weight 1× in a month
Nascimento, S.; Murray, W.; Wilson, P.
Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)
Nascimento, S.; Murray, W.; Wilson, P. [Pittwater Radiology, Dee Why, NSW, (Australia)
Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors). 11 refs., 6 figs.
Brown, C M
Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up.
Bevan, M J
A microsomal preparation from a mouse plasmacytoma, MOPC 47A, that secretes immunoglobulin A was used to study the release of nascent immunoglobulin peptides in vitro. Nascent chains were released with puromycin and characterized with specific antiserum against the immunoglobulin product of the tumour. When the tissue had been prelabelled with [(3)H]leucine the experiments were complicated by the large background of completed radioactive polypeptides in the microsomal preparation. Up to one-third of the released radioactivity in the microsomal preparation could be recognized as immunoglobulin. With [(3)H]-puromycin as the radioactive label, however, the results are much easier to interpret, although the proportion of released radioactivity that can be identified as immunoglobulin is lower (up to one-tenth). Both types of experiment demonstrate that all of the recognizable nascent immunoglobulin chains remain in association with the microsomal vesicles after release from the ribosomes.
Krishman, E.C.; Jewell, W.R.
A radioimmunoassay techniques developed to quantitatively measure the presence of immunoglobulins on the surface of cells, is described. The amount of immunoglobulins found on different tumor cells varied from 200 to 1140 ng/10 6 cells. Determination of immunoglobulins on the peripheral lymphocytes obtained from different cancer patients varied between 340 to 1040 ng/10 6 cells. Cultured tumor cells, on the other hand, were found to contain negligible quantities of human IgG [pt
Soto, G; Naranjo González, M; Calero, F
Systemic lidocaine used in continuous infusion during the peri-operative period has analgesic, anti-hyperalgesic, as well as anti-inflammatory properties. This makes it capable of reducing the use of opioids and inhalational anaesthetics, and the early return of bowel function, and patient hospital stay. The aim of this narrative review was to highlight the pharmacology and indications for clinical application, along with new and interesting research areas. The clinical applications of peri-operative lidocaine infusion have been reviewed in several recent systematic reviews and meta-analyses in patients undergoing open and laparoscopic abdominal procedures, ambulatory procedures, and other types of surgery. Peri-operative lidocaine infusion may be a useful analgesic adjunct in enhanced recovery protocols. Potential benefits of intravenous lidocaine in chronic post-surgical pain, post-operative cognitive dysfunction, and cancer recurrence are under investigation. Due to its immunomodulation properties over surgical stress, current evidence suggests that intravenous lidocaine could be used in the context of multimodal analgesia. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Gautvik, K.M.; Svindahl, K.; Skretting, A.; Stenberg, B.; Myhre, L.; Ekeland, A.; Johannesen, J.V.
A medullary carcinoma of the thyroid gland (MCT) which has been transplanted repeatedly under the kidney capsule of Wag/Rij rats secretes calcitonin (CT) spontaneously. From 10-20 weeks after transplantation, immunoreactive serum calcitonin (iCT) is abnormally elevated and continues to rise parallel to tumor growth. The immunoglobulin fraction of the rabbit anti-CT antiserum raised against intact synthetic hormone, was purified and iodinated electrolytically. Specific activities of 131 I-labeled immunoglobulin of 0.008-0.014 mCi/μg protein were obtained with 80% preservation of CT binding activity. Wag/Rij rats with MCT tumor and increased serum iCT concentrations received intravenous injections of 131 I-labeled immunoglobulins (0.54-0.811 mCi). The distribution of radioactivity in the rats was followed for 14 days using external scintigraphy in combination with radioactivity measurements of blood and different organs at the end of the observation period. The distribution of /sup 113m/In was used as a marker for blood distribution. When the radioactivity ratios ( 131 I//sup 113m/In) in tumor and different organs were related to that of blood which was equal to unity, tumor tissue contained 3-6 times higher activity. Nonhyperimmune rabbit immunoglobulins or rabbit antirat prolactin immunoglobulins were not concentrated in MCT tissue, nor did anti-CT immunoglobulins localize in rat prolactin adenomas
Gautvik, K.M.; Svindahl, K.; Skretting, A.; Stenberg, B.; Myhre, L.; Ekeland, A.; Johannesen, J.V.
A medullary carcinoma of the thyroid gland (MCT) which has been transplanted repeatedly under the kidney capsule of Wag/Rij rats secretes calcitonin (CT) spontaneously. From 10--20 weeks after transplantation, immunoreactive serum calcitonin (iCT) is abnormally elevated and continues to rise parallel to tumor growth. The immunoglobulin fraction of the rabbit anti-CT antiserum raised against intact synthetic hormone, was purified and iodinated electrolytically. Specific activities of 131 I-labeled immunoglobulin of 0.008--0.014 mCi/microgram protein were obtained with 80% preservation of CT binding activity. Wag/Rig rats with MCT tumor and increased serum iCT concentrations received intravenous injections of 131 I-labeled immunoglobulins (0.054--0.811 mCi). The distribution of radioactivity in the rats was followed for 14 days using external scintigraphy in combination with radioactivity measurements of blood and different organs at the end of the observation period. The distribution of 113 mIn was used as a marker for blood distribution. When the radioactivity ratios ( 131 I/ 113 mIn) in tumor and different organs were related to that of blood which was set equal to unity, tumor tissue contained 3--6 times higher activity. Nonhyperimmune rabbit immunoglobulins or rabbit antirat prolactin immunoglobulins were not concentrated in MCT tissue, nor did anti-CT immunoglobulins localize in rat prolactin adenomas
Lim, Lee-Moay; Chang, Jer-Ming; Wang, I-Fang; Chang, Wei-Chiao; Hwang, Daw-Yang; Chen, Hung-Chun
X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton's tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant. We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted. We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.
Hoorn, Ewout J
The topic of intravenous (IV) fluids may be regarded as "reverse nephrology", because nephrologists usually treat to remove fluids rather than to infuse them. However, because nephrology is deeply rooted in fluid, electrolyte, and acid-base balance, IV fluids belong in the realm of our specialty. The field of IV fluid therapy is in motion due to the increasing use of balanced crystalloids, partly fueled by the advent of new solutions. This review aims to capture these recent developments by critically evaluating the current evidence base. It will review both indications and complications of IV fluid therapy, including the characteristics of the currently available solutions. It will also cover the use of IV fluids in specific settings such as kidney transplantation and pediatrics. Finally, this review will address the pathogenesis of saline-induced hyperchloremic acidosis, its potential effect on outcomes, and the question if this should lead to a definitive switch to balanced solutions.
Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.
High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...
Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.
Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)
Kruljec, Nika; Bratkovič, Tomaž
The demand for recombinant therapeutic antibodies and Fc-fusion proteins is expected to increase in the years to come. Hence, extensive efforts are concentrated on improving the downstream processing. In particular, the development of better-affinity chromatography matrices, supporting robust time- and cost-effective antibody purification, is warranted. With the advances in molecular design and high-throughput screening approaches from chemical and biological combinatorial libraries, novel affinity ligands representing alternatives to bacterial immunoglobulin (Ig)-binding proteins have entered the scene. Here, we review the design, development, and properties of diverse classes of alternative antibody-binding ligands, ranging from engineered versions of Ig-binding proteins, to artificial binding proteins, peptides, aptamers, and synthetic small-molecular-weight compounds. We also provide examples of applications for the novel affinity matrices in chromatography and beyond.
The present study was performed to compare the clinical value of urography and ultrasonography in a non-selected group of patients referred for urography to a university hospital. The conslusions and clinical implications of the study are as follows: Intravenous urography remains the cornerstone imaging examination in the evaluation of ureteral calculi. Ultrasonography is a valuable adjunct in cases of non- visualization of the kidneys, in distal obstruction and known contrast media allergy. When women with recurrent urinary tract infection are referred for imaging of the urinary tract, ultrasonography should be used. Ultrasonography should replace urography for screening of non-acute hydronephrosis like in female genital cancer and benign prostate hyperplasia. There is good correlation between urography and ultrasonography in assessing the degree of hydronephrosis. However, more researh on the relationship between hydronephrosis and obstruction is necessary. Ultrasonography should be used as the only imaging method of the upper urinary tract in patients with microscopic hematuria. In patients less than 50 years with macroscopic hematuria, ultrasonography should be used as the only imaging of the upper urinary tract, and an examination of the urinary bladder should be included. In patients over 50 years, urography supplied with ultrasonography should be used, but more research is necessary on the subject of imaging method and age. 158 refs
I Gusti Ayu Agung Suartini
Full Text Available Canine parvovirus (CPV is a highly infectious virus. The virus causes death in dogs worldwide. The mortality rate due to infection of CPV in dog reaches 91%. Prevention of CPV infection in puppies has been done by vaccination which is effectively proven. Protective mechanisms of maternal antibodies contribute to the failure of vaccination. Highly stable characteristics of parvovirus enable the virus still exist in the environment. Various therapies are performed only to suppress the clinical symptoms but can not reduce puppy mortalities. This review discusses CPV alternative therapy and the advantages using immunoglobulin Y (IgY specific antibodies isolated from chicken egg yolk. Immunoglobulin Y will neutralize the virus, so it can not infect host cells. Intravenous IgY therapy has shown to suppress the spread of CPV infection and prevent death.
Hurley, Walter L.; Theil, Peter K.
Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105
Budsky, F.; Prokop, J.; Hradil, M.
The general principles are briefly described of labelling immunoglobulins with metal radionuclides. Bicyclic anhydrides cDTPAA and cEDTAA were selected for experiments by the Nuclear Research Institute at Rez near Prague. The compounds show sufficient reactivity to immunoglobulins and can be stored in an evacuated dessicator with calcium chloride at laboratory temperature for an unlimited time. The procedure is described of the preparation of the two anhydrides and of their labelling with 111 In and 99m Tc. For both radionuclides, favourable results have been obtained in labelling immunoglobulins, which creates preconditions for the introduction of immunoscintigraphy in Czechoslovak nuclear medicine. (Z.M.). 3 tabs., 13 refs
cyclophosphamide, gold, dapsone and mycophenolate mofetil have an adjunctive role to improve response to corticosteroids and also for their corticosteroid- sparing effect. Intravenous Immunoglobulin (IVIG) have recently come on board as effective though expensive treatment agents . In extremely resistant cases complex.
Items 951 - 1000 of 1463 ... Vol 11 (2011): Special Issue, Patient satisfaction with health care services provided at HIV clinics at Amana and Muhimbili hospitals in Dar es ... Vol 13, No 2 (2013), Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting, Abstract PDF.
van Schaik, I. N.; Bouche, P.; Illa, I.; Léger, J.-M.; van den Bergh, P.; Cornblath, D. R.; Evers, E. M. A.; Hadden, R. D. M.; Hughes, R. A. C.; Koski, C. L.; Nobile-Orazio, E.; Pollard, J.; Sommer, C.; van Doorn, P. A.
Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus
van der Sanden, Sabine M. G.; Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M.; de Jong, Menno D.; Wolthers, Katja C.
Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from
Kraus, Dror; Konen, Osnat; Straussberg, Rachel
Schilder's disease (SD) is a rare variant of multiple sclerosis with a predilection to children. It is characterized by focal neurological abnormalities, which are atypical for MS, in conjunction with tumor-like white matter lesions on MRI. We report the case of an 11-year-old girl that demonstrates two important features of the disease: a) the clinical presentation and subsequent course in conjunction with the serial neuroradiological findings stress the feasibility of a non-invasive diagnosis of SD; and b) we report a significant clinical response to treatment with intravenous human Immunoglobulins. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien
Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.
The immunoglobulin profiles of 126 Nigerian children infected with Plasmodium falciparum in their peripheral blood were investigated. The mean malarial parasitaemia was 4699.17 ± 3695.2 ìl. The mean immunoglobulin profile of these infected children were 2.68 ± 0.019 mg/dl for IgA, 0.031 ± 0.01 mg/dl for IgD, 1358.29 ...
Cohen, J B; Givol, D
The 12 immunoglobulin VH pseudogenes, that have been characterized to date, differ from most pseudogenes of other multigene families in two aspects: (i) they carry only one (11 cases) or at the most two (1 case) deleterious mutations and (ii) they show no evidence of increased divergence from intact VH genes. We describe here the first immunoglobulin VH pseudogene that does not have these characteristics. This pseudogene accumulated numerous deleterious mutations and diverged considerably fro...
Schroeder, Harry W; Cavacini, Lisa
Immunoglobulins are heterodimeric proteins composed of two heavy (H) and two light (L) chains. They can be separated functionally into variable (V) domains that binds antigens and constant (C) domains that specify effector functions such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events, and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each V domain can be split into three regions of sequence variability, termed the complementarity determining regions, or CDRs, and four regions of relatively constant sequence termed the framework regions, or FRs. The three CDRs of the H chain are paired with the three CDRs of the L chain to form the antigen binding site, as classically defined. There are five main classes of heavy chain C domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into four subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties; and IgA can similarly be split into IgA1 and IgA2. The constant domains of the H chain can be switched to allow altered effector function while maintaining antigen specificity. PMID:20176268
S.W.A. Tjon (Angela)
markdownabstract__Abstract__ Immunity originates from the Latin term immunis, meaning “exempt”, which refers to all the mechanisms used by the body as protection against invasion by agents that are foreign to the body. These agents may be infectious pathogens, foods, chemicals, drugs, and, in
Fazekas, F.; Lublin, F.D.; Li, D.
-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity...
Sag, Aslihan Taskiran; Saka, Esen; Ozgur, Tuba Turul; Sanal, Ozden; Ayvaz, Deniz Cagdas; Elibol, Bulent; Kurne, Asli Tuncer
A progressive encephalopathy of unknown etiology has been described in patients with primary immunodeficiency disorders. In this report, we characterize the clinical features of this progressive neurodegenerative dementing disorder in a young man with Bruton agammaglobulinemia, through neuropsychological tests and a video sequence. The clinical course of the encephalopathy seems rather uniform: Cognition, especially frontal lobe function, is affected in the early stages, and some patients develop movement disorders. The syndrome causes severe cognitive and physical disability, and can eventually be fatal. The autoimmunity results from dysregulated immune responses, but the underlying mechanism has not yet been fully explained.
Pranzatelli, Michael R; Allison, Tyler J; Tate, Elizabeth D
Flow cytometric cerebrospinal fluid (CSF) lymphocyte subset analysis has improved the diagnosis of neuroinflammation and identified multiple markers of inflammation in opsoclonus-myoclonus syndrome (OMS). The aim of this exploratory, retrospective study was to analyze the effect of immunotherapy on these markers to determine which agents are disease modifying. Cross-sectional immunological observations were made in an IRB-approved case-control study, and patients were treated empirically. Ten different CSF lymphocyte subpopulations from 18 children with persistent OMS had been measured by flow cytometry before and after clinical treatment with cyclophosphamide/ACTH/IVIG combination (n = 7) or ACTH/IVIG alone (n = 11). Clinical severity of OMS was scored from videotapes by a blinded observer using the OMS Evaluation Scale. Only cyclophosphamide combination therapy (mean dose 26 ± 3 mg/kg or 922 ± 176 mg/m 2 x 6 cycles) significantly decreased the percentage of CSF B cells. The mean reduction was 65%, with CSF B cell frequency normalized at 7-8 months in 70%. Other abnormalities of the CSF immunophenotype, such as the low CD4/CD8 T cell ratio, persisted, and there were no therapeutic changes in T cell activation/maturation markers. Effects on relative and absolute size of PBMC subsets were similar. Clinical improvement was 70% and 55% in respective treatment groups. The relapse rates of the two groups did not significantly differ. The main effect of cyclophosphamide combination therapy on neuroinflammation in OMS was moderate reduction in CSF B cell expansion. Though exploratory, it may provide a steroid sparer option in partially-responsive OMS. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Ghekiere, Olivier; Galant, Christine; Berg, Bruno Vande [Cliniques Universitaires St. Luc, Department of Radiology, Brussels (Belgium)
Lobular capillary hemangioma is a vascular neoplasm that commonly occurs as a cutaneous tumor. When it involves the skin and mucosal surfaces, ulceration and suppuration may occur, hence the classic term of pyogenic granuloma. Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report the ultrasonographic and magnetic resonance imaging findings of a pyogenic intravenous granuloma localized in the right cephalic vein. The imaging and pathological findings and the differential diagnoses are discussed. (orig.)
Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.
Riera, Francisco; Alvarez, Alejandro; Espi, Alberto; Prieto, Miguel; de la Roza, Begoña; Vicente, Fernando
Adult Holstein cows were injected with an antiserum against Campylobacter jejuni and immunoglobulin activities in vitro were determined in blood and milk several weeks after injection. The immunoactivity of immunoglobulins in milk was measured by an ELISA after different temperature-time treatments (60-91°C and 4-3600 s) at laboratory and pilot-plant scales. Kinetic and thermodynamic parameters were determined. An increase in immunoglobulin activity in milk was detected several days after injection. Optical densities increased by three- to seven-fold in this period. The activity started to decay 4-5 weeks after injection. Immunoglobulins maintained most of their in vitro activity under pasteurisation conditions (72°C and 15 s) and were denatured following first-order kinetics. The injection protocol applied allows milk with specific immunoglobulins against Campylobacter jejuni to be obtained. Traditional pasteurisation did not reduce this activity. © 2013 Society of Chemical Industry.
Shan H. Siddiqi
Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.
Treatment with high-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins in patients with juvenile dermatomyositis who are intolerant to intravenous immune globulins: a report of 5 cases.
Speth, Fabian; Haas, Johannes-Peter; Hinze, Claas H
High-dose intravenous immune globulins (IVIg) are frequently used in refractory juvenile dermatomyositis (JDM) but are often poorly tolerated. High-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins (fSCIg) allow the administration of much higher doses of immune globulins than conventional subcutaneous immune globulin therapy and may be an alternative to IVIg. The safety and efficacy of fSCIg therapy in JDM is unknown. In this retrospective case series, five patients with steroid-refractory severe JDM were treated with high-dose fSCIg due to IVIg adverse effects (severe headaches, nausea, vomiting, difficult venous access). Peak serum IgG levels, muscle enzymes, the childhood myositis assessment scale and adverse effects were retrieved for at least 6 months following intiation of fSCIg. Data were analyzed by descriptive statistics. Patients initially received fSCIg 1 g/kg every 14 days, resulting in median IgG peak levels of 1901 mg/dl (1606-2719 mg/dl), compared to median IgG peak and trough levels while previously receiving IVIg of 2741 mg/dl (2429-2849 mg/dl) and 1351 mg/dl (1156-1710 mg/dl). Additional antirheumatic therapies consisted of low-dose glucocorticoid therapy, methotrexate, mycophenolate mofetil and/or rituximab. Two patients maintained clinically inactive disease and three patients had only a partial treatment response. In the three patients with partial treatment response, fSCIg 1 g/kg was then given on days 1 and 6 of every 28-day cycle resulting in IgG peak levels of between 2300-2846 mg/dl (previously 1606-1901 mg/dl on the biweekly regimen), resulting in clinically inactive disease in two of the three patients. There were no relevant adverse effects that limited continuation of fSCIg treatment. High-dose fSCIg is well-tolerated in patients with JDM and high peak serum IgG levels can be achieved which may be important for treatment success. High-dose fSCIg may therefore be an alternative to high-dose IVIg
Östlund, Gunilla; Broman, Lisbet; Werhagen, Lars; Borg, Kristian
To define and characterize responders and non-responders in a group of 124 patients with post-polio syndrome who received a single treatment with intravenous immunoglobulin. Open trial, prospective follow-up study. Clinical examination and data from medical records. Short Form 36 (SF-36), Physical Activity Scale for the Elderly (PASE) and visual analogue scale (VAS) measured quality of life, physical activity and intensity of pain, respectively. Data were obtained before treatment and at 6-month follow-up. Two responder groups were identified with the outcome SF-36 Vitality and 3 with Bodily pain, respectively. Forty-five percent were positive-responders, identified before treatment by reduced physical function, muscle atrophy in the lower extremities, higher levels of fatigue and pain, and a VAS pain score above 20. Negative-responders were identified by good physical function and mental health, lesser muscle atrophy in the lower extremities, and low levels of fatigue and pain. Intravenous immunoglobulin is a biological intervention, and therefore it is important to be able to identify responders and non-responders. In order to maximize a positive outcome it is suggested that patients with a high level of fatigue and/or pain and reduced physical function are selected.
Hurley, W L; Theil, Peter Kappel
Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide...... a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases......, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes...
Okorie, N. M.; MacKinnon, A. E.
Results of intravenous urography (IVU) in 33 patients suspected of suffering from renal trauma were reviewed. It was concluded that when haematuria is only detected microscopically and clears within 24 hr then an IVU is not necessary, in the absence of other evidence of significant urinary tract injury.
Sklyar I. V.
Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.
Mots clés: Immunoglobulines E, allergie, Togo. English Abstract. Place of total immunoglobulin E dosage in common practice in Togo. Objective: to determine the place of total immunoglobulin E (IgE) dosage in common practice in Togo. Material and methods: 650 total IgE dosages performed during 4 years (2008 to 2011) ...
Butler, J. E.; Zhao, Y.; Šinkora, Marek; Wertz, N.; Kacskovics, I.
Roč. 33, č. 3 (2009), s. 321-333 ISSN 0145-305X R&D Projects: GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : swine * immunoglobulin * b cell Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009
Kubrycht, J.; Sigler, Karel; Růžička, Michal; Souček, P.; Borecký, J.; Ježek, Petr
Roč. 63, - (2006), s. 691-706 ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509 Keywords : immunoglobulin * hypermutation * antigen Subject RIV: EE - Microbiology, Virology Impact factor: 2.767, year: 2006
Fernandez-Cruz, E.; Kaveri, S. V.; Peter, H.-H.; Durandy, A.; Cantoni, N.; Quinti, I.; Sorensen, R.; Bussel, J. B.; Danieli, M. G.; Winkelmann, A.; Bayry, J.; Käsermann, F.; Späth, P.; Helbert, M.; Salama, A.; van Schaik, I. N.; Yuki, N.
The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on
Fernandez-Cruz, E.; Kaveri, S.V.; Peter, H.H.; Durandy, A.; Cantoni, N.; Quinti, I.; Sorensen, R.; Bussel, J.B.; Danieli, M.G.; Winkelmann, A.; Bayry, J.; Kaesermann, F.; Spaeth, P.; Helbert, M.; Salama, A.; van Schaik, I.N.; Yuki, N.
P>The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on
... Blood Test: Immunoglobulin A (IgA) What's in this article? What It Is Why It's Done Preparation The Procedure What to Expect Getting the Results Risks Helping Your Child If You Have Questions Print en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA ...
Adsorption of immunoglobulin G (IgG) is a common step in the production of immunological tests and biosensors. The use of IgG in these applications stems from its ability to specifically bind all kinds of molecules (antigens). In these tests the IgG
Kuijpers, Taco W.; Vendelbosch, Sanne; van den Berg, Merlijn; Baeten, Dominique L. P.
We focus on the role of killer immunoglobulin receptor (KIR) interactions with the human leukocyte antigens (HLA)-B27 ligand and the potential contribution of KIR-expressing natural killer and T cells in spondyloarthritis, more specifically in ankylosing spondylitis (AS). In AS strong
P. N. Vlasov
Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed.
Full Text Available Intravenous sedation is effective to reduce fear and anxiety in dental treatment. It also has been used for behavior modification technique in dental patients with special needs. Midazolam and propofol are commonly used for intravenous sedation. Although there have been many researches on the effects of midazolam and propofol on vital function and the recovery profile, little is known about muscle power. This review discusses the effects of intravenous sedation using midazolam and propofol on both grip strength and bite force. During light propofol sedation, grip strength increases slightly and bite force increases in a dose-dependent manner. Grip strength decreases while bite force increases during light midazolam sedation, and also during light sedation using a combination of midazolam and propofol. Flumazenil did not antagonise the increase in bite force by midazolam. These results may suggest following possibilities; (1 Activation of peripheral benzodiazepine receptors located within the temporomandibular joint region and masticatory muscles may be the cause of increasing bite force. (2 Propofol limited the long-latency exteroceptive suppression (ES2 period during jaw-opening reflex. Thus, control of masticatory muscle contraction, which is thought to have a negative feedback effect on excessive bite force, may be depressed by propofol.
Dong Hoon Lee
Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.
Koehler, A.H.; Stoeck, R.
In 115 operated patients with breast cancer of the TNM-B stages 1-3 the levels of immunoglobulins A, G and M were determined before and after radiotherapy. The results show that radiotherapy does not bring about significant change of the levels of immunoglobulins. Therefore the determination of the immunoglobulins is not suitable both for prognostic statements and as indicator of immunologic changes during radiotherapy. (author)
O. V. Moskalets
Full Text Available Selective immunoglobulin A (IgA deficiency is considered to be the most common primary immune deficiency. Up to now, no specific genetic mutation causing this disorder has been found. True prevalence of selective IgA deficiency in the population is unknown, because in most cases it is asymptomatic and occurs as an incidental laboratory finding. In some patients, it can manifest by respiratory and gastrointestinal infections, as well as allergic and autoimmune disorders. According to the literature, autoimmune disorders in patients with selective IgA deficiency have a more aggressive course and a worse prognosis. This clinical case of a combination of selective IgA deficiency and autoimmune gastritis demonstrates that patients with primary immunodeficiency, especially adults, may not know about their disease for a long time. The paper may be of interest for practicing doctors of various specialties, first of all, for gastroenterologists, internists, general practitioners, and is intended to increase awareness about diagnosis of selective IgA deficiency. There is no specific treatment for this immunodeficiency, but one should bear in mind that blood transfusions and intravenous immunoglobulin preparations with high IgA content are contra-indicated in these patients due to a high risk of anaphylactic reactions.
Gilbert, Ruth E; Thalib, Lukman; Tan, Hooi Kuan
OBJECTIVES: To determine the accuracy of postnatal screening for toxoplasma-specific immunoglobulin (Ig) M and IgA. SETTING: Ten centres in three European countries. METHODS: We compared results of the first postnatal IgM or IgA test in infants with infected mothers identified by prenatal screeni...
Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.
Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.
In this review article, the local and systemic complications of intravenous therapy are highlighted and their preventive measures are discussed. Intravenous therapy exposes the patient to numerous hazards and many of them are avoidable, if the health care provider understands the risks involved and acts appropriately and ...
Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.
Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah
Panniculitis is an inflammatory disease of subcutaneous adipose tissue which is rarely associated with dermatomyositis. It can occur before, after or simultaneously with muscle damage. In most cases, the evolution of panniculitis and of other dermatomyositis affections is favorable with corticosteroids and/or immunosuppressants. We report the case of a 48 year-old patient who developed panniculitis lesions 2 months before having muscular signs. Skin involvement was resistant to corticosteroid treatment associated with immunosuppressants drugs. This led to the use of polyvalent immunoglobulin treatment improving both skin and muscle damage.
... Search Patient Resources Adult Immunoglobulin Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when you ... germ-fighting antibodies. A treatment known as immunoglobulin replacement (IgG) therapy can be a lifesaver for them. ...
Pettinello, Rita; Dooley, Helen
Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.
Fujiwara, Saeko; Akahoshi, Masazumi; Kodama, Kazunori; Shimaoka, Katsutaro; Akiyama, Mitoshi; Carter, R.L.; Yamakido, Michio
The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE. 32 refs., 2 figs., 3 tabs
Jonsson, Stefan; Sveinbjornsson, Gardar; de Lapuente Portilla, Aitzkoa Lopez; Swaminathan, Bhairavi; Plomp, Rosina; Dekkers, Gillian; Ajore, Ram; Ali, Mina; Bentlage, Arthur E H; Elmér, Evelina; Eyjolfsson, Gudmundur I; Gudjonsson, Sigurjon A; Gullberg, Urban; Gylfason, Arnaldur; Halldorsson, Bjarni V; Hansson, Markus; Holm, Hilma; Johansson, Åsa; Johnsson, Ellinor; Jonasdottir, Aslaug; Ludviksson, Bjorn R; Oddsson, Asmundur; Olafsson, Isleifur; Olafsson, Sigurgeir; Sigurdardottir, Olof; Sigurdsson, Asgeir; Stefansdottir, Lilja; Masson, Gisli; Sulem, Patrick; Wuhrer, Manfred; Wihlborg, Anna-Karin; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Vidarsson, Gestur; Jonsdottir, Ingileif; Nilsson, Björn; Stefansson, Kari
Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10 -55 , β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10 -8 , β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
Kamran Mousavi Hosseini
Full Text Available Human plasma proteins are important for therapy or prophylaxis of human diseases. Due to the preparation of human plasma proteins from human plasma pools and risk of contamination with human viruses, different viral reduction treatments such as: pasteurization, solvent/detergent, dry heat treatment, steam treatment, beta-propiolactone/UV and nanofiltration have been implemented. As pasteurization can be performed for liquid protein, this method (a 10-hour heat treatment of the aqueous solutions at 60°C was introduced into the manufacturing procedure of IgM-enriched immunoglobulin, to improve its safety further. The efficiency of this method for inactivation of viruses was evaluated by the use of Foot-and-Mouth Disease Virus (a non-enveloped virus and Infectious Bovine Rhinotracheitis (IBR Virus (a lipid-enveloped virus. Pasteurization inactivated Foot-and-Mouth Disease Virus by 7 log10 and for IBR Virus by 5log10. These findings show a significant added measure of virus safety associated with pasteurization of IgM-enriched immunoglobulin preparation.
Full Text Available Scabies is one of the most important diseases in human and veterinary medicine. The available control measures that rely on acaricides are unsustainable, costly and environmentally unfriendly. Vaccination which is supposedly the most attractive alternative control, is sustainable, potentially cheap and environmentally friendly. Recent development in protein biochemistry and recombinant technology have facilitated the development of anti-parasite vaccine which in the past was impossible. One prerequisite for the anti-parasite-vaccine development is that the parasite has to ingest its host immunoglobulin. This study, therefore, was designed to determine whether Sarcoptes scabiei, a non blood-feeding parasite that resides on the avascular cornified layer of the skin, ingest its host immunoglobulin. Sections of routinely processed mites and skin from a mangy goat were probed with peroxidase-conjugated-anti-goat IgG and the immune complex was visualised with diaminobenzidine solution. To determine whether the ingested IgG was still intact or had been fragmented by the proteolytic enzymes, immunoblotting analysis of SDS-PAGE- fractionated proteins extracted from washed mites was performed. Quantification of IgG was done byan Elisa using purified goat IgG as control. This study showed that IgG in the mites confined to the mite’s gut only, and only a fraction of mite population ingested the IgG. The ingested IgG, as shown by immunoblot analysis, was mostly still intact. This study indicates that development of anti-scabies vaccines is reasonable.
Rajendra P Maurya
Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.
Joyce, J.M.; Grossman, S.J.; Garrett, J.S.; Sharma, B.; Geller, M.; Sweeney, P.J.
This paper determines the safety and efficacy of intravenous (IV) adenosine in females for the evaluation of coronary artery disease, since only limited data are available. Eighty consecutive studies of 78 female subjects (aged 43-83 years) using IV adenosine (0.14 mg/kg per minute) with T1-201 SPECT imaging were reviewed. Fifty-eight (73%) had mild symptoms; mild dyspnea (24%), flushing (23%), chest pain (23%), headache (11%), dizziness (11%), weakness (9%), nausea (8%), abdominal pain (8%), arm pain (6%), chest tightness (4%), neck tightness (4%), dry mouth (4%), and dropped P waves (4%). Four had moderate symptoms: dyspnea requiring Proventil or aminophylline (2%), significant hypotension (1%), and third-degree atrioventicular heart block (1%). Two had severe symptoms (ventricular tachycardia requiring cardioversion (1%) and severe dyspnea requiring epinephrine (1%). Twenty-two (28%) underwent cardiac catheterization that demonstrated coronary artery disease or postangioplasty results. The thallium SPECT images were 94% sensitive and 100% specific in detecting significant disease. The one false-negative result was in a subject who experienced no symptoms for ECG changes during adenosine infusion. Ischemic ECG changes were 35% sensitive and 100% specific. Chest pain was 53% sensitive and 60% specific
Olivieri, David N; Garet, Elina; Estevez, Olivia; Sánchez-Espinel, Christian; Gambón-Deza, Francisco
The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA-seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one Cμ gene which is located downstream from the Cδ gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the λ light chain, only Iguanidae species possess the κ light chain. Copyright © 2016 Elsevier Ltd. All rights reserved.
Martin-Loeches, Ignacio; Muriel-Bombín, Arturo; Ferrer, Ricard; Artigas, Antonio; Sole-Violan, Jordi; Lorente, Leonardo; Andaluz-Ojeda, David; Prina-Mello, Adriele; Herrán-Monge, Ruben; Suberviola, Borja; Rodriguez-Fernandez, Ana; Merino, Pedro; Loza, Ana M; Garcia-Olivares, Pablo; Anton, Eduardo; Tamayo, Eduardo; Trapiello, Wysali; Blanco, Jesús; Bermejo-Martin, Jesús F
Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan-Meier and multivariate logistic regression analysis. ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the
Von Schenck, H.; Grubb, A.O.
Radioimmunoassays of glucagon in plasma may be complicated by interaction with other substances of high molecular mass. Precipitates of such substances with ammonium sulfate showed, after isoelectric focusing, two fractions having glucagon immunoreactivity. One fraction (pI approx.10) evidently is associated with the Fc portion (but not the Fab portion) of purified polyclonal immunoglobulin G (IgG). Equal amounts of purified monoclonal IgG of various subclasses, especially IgG 1, gave different ''glucagon'' readings, suggesting that some IgG may interfere more strongly than others. The other fraction (pI 5-6) appeared less consistently, and on gel chromatography appeared to be slightly larger than IgG. Together these fractions add about 50-100 ng/L to the immunoreactive glucagon values in plasma. Therefore methods in which glucagon is extracted before assay should be used for determining the concentration of glucagon present physiologically
The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.
E. Y. Ponomareva
Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.
A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.
Tosch, U.; Becker-Gaab, C.; Hahn, D.
Aetiology and diagnostic procedure of calyceal fornix rupture during intravenous urography are discussed. In the literature the fornix rupture is discribed as a spontaneous event - not so in the four cases presented. In two cases a sudden increase in intrapelvic pressure was due to an ureteric calculus, in the other cases an obstruction of the ureter was secondary to neoplasm. It is recommended to perform a CT as soon as a contrastmedium extravasation in intravenous urography is diagnosed. (orig.) [de
Tosch, U.; Becker-Gaab, C.; Hahn, D.
Aetiology and diagnostic procedure of calyceal fornix rupture during intravenous urography are discussed. In the literature the fornix rupture is discribed as a spontaneous event - not so in the four cases presented. In two cases a sudden increase in intrapelvic pressure was due to an ureteric calculus, in the other cases an obstruction of the ureter was secondary to neoplasm. It is recommended to perform a CT as soon as a contrast medium extravasation in intravenous urography is diagnosed.
Perez-del-Pulgar, S; Lopez, M; Gensana, M; Jorquera, J I
Preparations of intravenous immunoglobulins must keep functional integrity throughout the purification process. In order to assess Fc fragment functionality, the European Pharmacopoeia proposes the Test for Fc function of immunoglobulin (2.7.9), which is based on a rubella antigen of high titre. Sometimes, such antigen is difficult to obtain. In the present study, we develop the same assay using tetanus toxoid instead of rubella antigen, adapting the procedure for the use of tetanus toxoid. The comparison between rubella-based and tetanus-based assays showed that the slopes of the haemolysis curves were higher if red blood cells had been sensitised with the rubella antigen than with tetanus toxoid. Nonetheless, the tetanus-based assay gave satisfactory results and it could be a good alternative antigen target.
Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.
Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords
Nadri, Quaid; Althaf, Mohammed Mahdi
A number of neurological entities have been associated with systemic lupus erythematosus (SLE). Gullian-Barre syndrome (GBS) as a presenting feature of SLE remains uncommon with just 9 cases reported in the last half-century with the first case reported in 19641-9 (Table 1). We report a young female presenting with GBS in whom SLE and WHO class V lupus nephritis (LN) was subsequently diagnosed. The neurological symptoms partially responded to pulse methylprednisone, intravenous immunoglobulin (IVIG) and plasmapheresis.
Maggio, M.; Corsello, G.; Prinzi, E.; Cimaz, R.
Background Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. Methods We studied the clinical data ...
Bikdeli, Behnood; Strait, Kelly M; Dharmarajan, Kumar; Li, Shu-Xia; Mody, Purav; Partovian, Chohreh; Coca, Steven G; Kim, Nancy; Horwitz, Leora I; Testani, Jeffrey M; Krumholz, Harlan M
This study sought to determine the use of intravenous fluids in the early care of patients with acute decompensated heart failure (HF) who are treated with loop diuretics. Intravenous fluids are routinely provided to many hospitalized patients. We conducted a retrospective cohort study of patients admitted with HF to 346 hospitals from 2009 to 2010. We assessed the use of intravenous fluids during the first 2 days of hospitalization. We determined the frequency of adverse in-hospital outcomes. We assessed variation in the use of intravenous fluids across hospitals and patient groups. Among 131,430 hospitalizations for HF, 13,806 (11%) were in patients treated with intravenous fluids during the first 2 days. The median volume of administered fluid was 1,000 ml (interquartile range: 1,000 to 2,000 ml), and the most commonly used fluids were normal saline (80%) and half-normal saline (12%). Demographic characteristics and comorbidities were similar in hospitalizations in which patients did and did not receive fluids. Patients who were treated with intravenous fluids had higher rates of subsequent critical care admission (5.7% vs. 3.8%; p fluid treatment varied widely across hospitals (range: 0% to 71%; median: 12.5%). Many patients who are hospitalized with HF and receive diuretics also receive intravenous fluids during their early inpatient care, and the proportion varies among hospitals. Such practice is associated with worse outcomes and warrants further investigation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Detection of dentin antigenic fractions by salivary immunoglobulin G in patients undergoing orthodontic treatment. TMP Soares da Costa, S de Paula Ramos, MM Hidalgo, A Consolaro, SA Khan, EN Itano ...
Møller, H U; Bojsen-Møller, M; Schrøder, H D
Three patients with granular corneal dystrophy Groenouw type I underwent corneal grafting, and cryostat sections of the corneal buttons were examined immunohistochemically for immunoglobulins. Positive results were obtained for IgG, Kappa-, and Lambda chains with immunofluorescence technique...
Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...
Leushuis, Esther; van der Steeg, Jan Willem; Steures, Pieternel; Repping, Sjoerd; Schöls, Willem; van der Veen, Fulco; Mol, Ben Willem J.; Hompes, Peter G. A.
Objective: To investigate the predictive capacity of immunoglobulin G ASA (direct MAR test) for spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Nine fertility centers in The Netherlands. Patient(s): Consecutive ovulatory subfertile couples.
Maisch, Bernhard; Hufnagel, Günther; Kölsch, Susanne; Funck, Rainer; Richter, Annette; Rupp, Heinz; Herzum, Matthias; Pankuweit, Sabine
of the beta-receptor antibody thus healing dilated cardiomyopathy. Application of this approach can be ranked level of evidence C, indication class IIb at present only. Therefore these two pathophysiologically attractive concepts have to await further validation by a double-blind, randomized clinical endpoint trial. It has been shown that immunoglobulins have both an antiviral and an anti-inflammatory effect. They may suppress proinflammatory cytokines and reduce oxidative stress. HIGH-DOSE I.V. In biopsy proven CMVmyocarditis a controlled trial demonstrated eradication of inflammation and of the virus (level of evidence B, indication class IIa), which is in accordance with registry data and case reports. In suspected myocarditis (not biopsy proven, no viral etiology established or excluded) conflicting data exist with respect to the improvement of surrogate markers such as the ejection fraction under high-dose immunoglobulins. More evidence can be weighted in favour of a positive treatment effect (level of evidence B, indication class IIb). Importantly there were no detrimental effects of the ivIG reported in these trials. One has to consider the high costs of this treatment, however. A trial taking into account the different etiologies (different viruses assessed separately vs. non-viral/autoreactive vs. placebo) is still lacking. MODERATE-DOSE I.V. Registry data support a positive effect of 20 g i.v. pentaglobin (IgG and IgM) in adenovirus positive myocarditis for clinical improvement, eradication of both the inflammation and the virus. In Parvo B19 myocarditis our own registry data indicate that clinical improvement can be noted, but only inflammation is successfully eliminated, whereas Parvo B19 persistence remains a problem in the majority of patients. In Parvo B19 associated DCMi therefore dose finding studies and randomized trials are needed.
Widders, P R; Stokes, C R; Newby, T J; Bourne, F J
This study identifies nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis. Immunoglobulin binding to the bacterium was strongest for immunoglobulin G (IgG) and less for IgM; IgA was not bound. Binding of equine IgG was inhibited by human IgG, but not by IgG of domestic animals. Immunoglobulin binding by the bacterium appeared to be directed towards an epitope in the hinge region of the immunoglobulin molecule.
Loraine Farias Landgraf; Nelson Augusto Rosário; Juliana Ferreira de Moura; Katherine Andrew Wells; Bonald Cavalcanti Figueiredo
Objective: To measure serum levels of immunoglobulin A byimmunoenzymatic assay (ELISA) in type 1 diabetes mellitus (DM-1)patients and to verify the prevalence of immunoglobulin A deficiency(IgAD) in diabetic patients. Methods: The serum immunoglobulin Alevel was determined in 149 DM-1 patients by three methods. IgADwas defined as serum immunoglobulin A level lower than 5 mg/dl.If serum immunoglobulin A level was undetectable by turbidimetry,radial immunodiffusion was performed in low plate co...
Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen
was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were...... associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown....
Bager, Palle; Dahlerup, Jens Frederik
What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients? It dependent on the economic evaluation perspective! Aim: To evaluate the health care cost for intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject......-cost per mg iron is for iron carboxymaltose approximately double the cost of iron sucrose. Patients and Methods: Data related to 111 IBD-patients treated with intravenous iron at Aarhus University Hospital from August 2005 until October 2009 was used for the economic evaluation. Analysis included......, utensils and ½ hour spend by a nurse per visit; showed approximately 150€ extra cost per 1000 mg Fe++ administrated, if iron carboxymaltose was chosen. In contrast the CEA including both BIA-values and patient-related costs (transportation and lost income) showed iron carboxymaltose to be more cost...
Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W
Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. © 2015 British Society for Immunology.
Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang
It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon. PMID:19246641
Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang
It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon.
Markvardsen, L H; Sindrup, S H; Christiansen, I
evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT.......2% (P = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% (P = 0.007), whereas grip strength, 40-MWT, 9-HPT and ODSS...
Henry Dunand, Carole J; Wilson, Patrick C
It is becoming evident that B-cell responses to particular epitopes or in particular contexts can be highly convergent at the molecular level. That is, depending on the epitope targeted, persons of diverse genetic backgrounds and immunological histories can use highly similar, stereotyped B-cell receptors (BCRs) for a particular response. In some cases, multiple people with immunity to a particular epitope or with a type of B-cell neoplasia will elicit antibodies encoded by essentially identical immunoglobulin gene rearrangements. In other cases, particular VH genes encode antibodies important for immunity against pathogens such as influenza and HIV. It appears that the conserved antibody structures driving these stereotyped responses are highly limited and selected. There are interesting and important convergences in the types of stereotyped BCRs induced in conditions of immunity and B-cell-related pathology such as cancer and autoimmunity. By characterizing and understanding stereotyped B-cell responses, novel approaches to B-cell immunity and in understanding the underlying causes of B-cell pathology may be discovered. In this paper, we will review stereotyped BCR responses in various contexts of B-cell immunity and pathology. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Kuijpers, Taco W; Vendelbosch, Sanne; Berg, Merlijn van den; Baeten, Dominique L P
We focus on the role of killer immunoglobulin receptor (KIR) interactions with the human leukocyte antigens (HLA)-B27 ligand and the potential contribution of KIR-expressing natural killer and T cells in spondyloarthritis, more specifically in ankylosing spondylitis (AS). In AS strong epidemiological evidence of significant genetic associations with the major histocompatibility complex was convincingly identified. HLA-B27-positive first-degree relatives of AS cases are 5-16 times more likely to develop disease than HLA-B27-positive carriers in the general community. The GWAS era has enabled rapid progress in identifying non-major histocompatibility complex associations of AS. These findings show a number of important pathways in AS pathogenesis, including the IL-23-IL-17 pathway, aminopeptidases, peptide presentation, and KIR-HLA-B27 interactions. Studies using genetic markers, including KIRs may be used for a risk assessment about whom may benefit most from the various treatment protocols in spondyloarthritis, now that alternative therapeutic options have become feasible.
Tapisiz, A; Polat, M; Kara, S S; Tezer, H; Simsek, H; Aktas, F
Since measles is a highly contagious respiratory infection with significant airborne transmission risk in hospitals, effective prevention measures are crucial. After a mother accompanying her child on a paediatric ward lacking a negative pressure room was diagnosed with measles, exposed persons without evidence of immunity (documentary evidence of receiving two doses of measles-mumps-rubella vaccine) were treated with vaccination or intravenous immunoglobulin (IVIG). The interruption of transmission with these treatments was evaluated. There were 44 children and 101 adults exposed to the index patient. Twenty-five children and 88 adults were considered immune, providing evidence of immunity. Nineteen children and 13 adults were either given vaccination or IVIG for post-exposure prophylaxis (PEP). There were no additional cases of measles after 3 weeks follow-up. We conclude that measles is highly preventable by adequate PEP with vaccination or IVIG in a healthcare setting that lacks the benefit of a negative pressure room.
Full Text Available Intravenous immunoglobulin administered at replacement dosages modulates innate and adaptive immune cells in primary antibody deficiencies (PAD in a different manner to what observed when high dosages are used or when their effect is analyzed by in vitro experimental conditions. The effects seem to be beneficial on innate cells in that dendritic cells maturate, pro-inflammatory monocytes decrease, and neutrophil function is preserved. The effects are less clear on adaptive immune cells. IVIg induced a transient increase of Treg and a long-term increase of CD4 cells. More complex and less understood is the interplay of IVIg with defective B cells of PAD patients. The paucity of data underlies the need of more studies on patients with PAD before drawing conclusions on the in vivo mechanisms of action of IVIg based on in vitro investigations.
K. Kuitwaard (Krista); P.A. van Doorn (Pieter); M. Vermeulen (Marinus); L.H. van den Berg (Leonard); E. Brusse (Esther); A.J. Kooj (Anneke); W.L. van der Pol (Ludo); I.N. van Schaik (Ivo); N.C. Notermans (Nicolette); A.P. Tio-Gillen (Anne); W. van Rijs (Wouter); T. van Gelder (Teun); B.C. Jacobs (Bart)
textabstractObjective: To determine the variability of serum IgG in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: All 25 CIDP patients had active but stable disease and were treated with individually optimised fixed dose IVIg regimens. IgG was measured by
Kuitwaard, Krista; van Doorn, Pieter A.; Vermeulen, Marinus; van den Berg, Leonard H.; Brusse, Esther; van der Kooi, Anneke J.; van der Pol, W.-Ludo; van Schaik, Ivo N.; Notermans, Nicolette; Tio-Gillen, Anne P.; van Rijs, Wouter; van Gelder, Teun; Jacobs, Bart C.
Objective To determine the variability of serum IgG in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods All 25 CIDP patients had active but stable disease and were treated with individually optimised fixed dose IVIg regimens. IgG was measured by turbidimetry and
Mau-Sørensen, Morten; Dittrich, Christian; Dienstmann, Rodrigo
design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab. Key DLTs were ≥grade 3 optimally treated non-hematological toxicity; ≥grade 3 infusion-related reactions refractory to supportive....... A reversible decrease in liver function test (prothrombin time) at the 7-µg dose level was considered a DLT. The first patient at 10 µg experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study. CONCLUSIONS: The MTD of weekly intravenous catumaxomab was 7 µg. Major...
Kwittken, P L; Sweinberg, S K; Campbell, D E; Pawlowski, N A
To better understand the clinical characteristics, diagnosis, and possible prevention of immediate hypersensitivity reactions to latex in a hospitalized, pediatric patient population. We performed a retrospective case analysis of the first 35 patients with latex allergy evaluated by our service over a 2-year period at our institution. Characteristics of patients and clinical reactions were analyzed and the presence of latex-specific immunoglobulin E was assessed using in vitro methods. In a limited group of patients, the success of strict environmental control and premedication with steroids and antihistamines was evaluated for the prevention of latex allergic reactions. The majority of our patients had life-threatening reactions. In previous reports, most pediatric patients underwent reactions in the perioperative period and belonged to two well-recognized "high-risk" patient groups (spina bifida and genitourinary malformations). In our series, 21 patients (60%) had reactions outside of the operating room setting, and 14 patients (40%) had primary diagnoses outside of the previously recognized "high-risk" groups. Many patients had a history of multiple surgical procedures, and a history of a surgical procedure in the first year of life was very common. A pre-existing clinical history of latex allergy was present in only 18 of the 35 patients, and a severe or life-threatening allergic reaction was the presenting feature of latex allergy in 11 of the 35 patients. Using in vitro assays, we were able to detect latex-specific immunoglobulin E in the sera of all but two of our patients. Latex gloves and latex-containing intravenous sets were common triggers for reactions. When exposure to latex occurs systemically, as through an intravenous line, premedication with steroids and antihistamines may fail to protect against anaphylaxis. Our experience indicates that the incidence of latex hypersensitivity in children is increasing, that the circumstances (patient profile
Yildiz, Inci; Ozdemir, Nihal; Celkan, Tiraje; Soylu, Selen; Karaman, Serap; Canbolat, Aylin; Dogru, Omer; Erginoz, Ethem; Apak, Hilmi
Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.
Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease characterized by intense polyclonal production of autoantibodies and circulating immune complexes. Some reports have associated SLE with a Th2 immune response and allergy. In the present study 21 female patients with SLE were investigated for total IgE and IgE antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent assay, and were also evaluated for antinuclear IgE autoantibodies by a modified indirect immunofluorescence test using HEp-2 cells as antigen substrate. Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median = 394 IU IgE/ml, was observed in 7 of 21 SLE patients (33%, 5 of them presenting proteinuria, urinary cellular casts and augmented production of anti-dsDNA antibodies. While only 2 of 21 SLE patients (9.5% were positive for IgE antibodies to aeroallergens, all 10 patients with respiratory allergy (100% from the atopic control group (3 males and 7 females, had these immunoglobulins. SLE patients and healthy controls presented similar anti-IgE IgG autoantibody titers (X = 0.37 ± 0.20 and 0.34 ± 0.18, respectively, differing from atopic controls (0.94 ± 0.26. Antinuclear IgE autoantibodies were detected in 17 of 21 (81% sera from SLE patients, predominating the fine speckled pattern of fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can present increased IgE levels and antinuclear IgE autoantibodies without specific clinical signs of allergy or production of antiallergen IgE antibodies, excluding a possible association between SLE and allergy.
Full Text Available Abstract Background Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost. Results We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames. A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3. Conclusions Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them.
Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando
Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders
Radhakrishnan, V V; Sumi, M G; Reuben, S; Mathai, A; Nair, M D
Tumour necrosis factor-alpha (TNF-alpha) is regarded as one of the immune factors that can induce demyelination of peripheral nerves in patients with Guillian-Barre syndrome (GBS). This present study was undertaken to find out the role of TNF-alpha and soluble TNF receptors in the pathogenesis of GBS; and to study the effect of intravenous immunoglobulin (ivIg) therapy on the serum TNF-alpha and soluble TNF receptors in patients with GBS. Thirty six patients with GBS in progressive stages of motor weakness were included in this study. The serum TNF-alpha and soluble TNF receptors (TNF-RI, TNF-RII) were measured in the serum samples of these patients before and after ivIg therapy by a sandwich ELISA. Of the 36 patients with GBS, 26 (72.2%) showed elevated serum TNF-alpha levels prior to ivIg therapy. Following a complete course of ivIg therapy there was a progressive decrease in the serum TNF-alpha concentrations in these 26 patients. On the other hand, the soluble TNF receptors, particularly TNF-RII showed an increase in the serum of GBS patients following ivIg therapy. The results indicate that ivIg reduces the serum TNF-alpha concentrations in the GBS patients having elevated levels prior to ivIg therapy. Elevated serum levels of soluble TNF receptors following ivIg therapy may play a protective role by inhibiting the demyelinating effect of TNF-alpha in the peripheral nerves of patients with GBS.
Svensson, Jannet; Eising, Stefanie; Mortensen, Henrik Bindesbøl
The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low...
Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.
Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all
Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.
BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in
Sep 3, 1993 ... parenterally, usually according to one of two popular regimens: the intramuscular (IM) regimen introduced by. Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! Sibai et a/.3 have reported that lower serum magnesium values are achieved with Zuspan's regimen (maintenance dose ...
The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...
Ephedrine is gradually falling out of favour because of the associated tachyarrhythmia and foetal acidosis. This study compared the effect of preoperative administration of intravenous glycopyrrolate and ephedrine on spinal induced maternal hypotension. Patients and Methods: Fifty patients scheduled for elective C/S were ...
Background: Renal ultrasonography an easily available procedure was compared to intravenous urogram (IVU) to determine its suitability as an alternative to the latter, which is a relatively invasive test for demonstrating hydronephrosis/ or ureteric obstruction in cervical cancer staging. Study design: Thirty five histologically ...
Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.
In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate
Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.
BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to
Background: Sedation in children remains a controversial issue in emergency departments (ED). Midazolam, as a benzodiazepine is widely used for procedural sedation among paediatrics. We compared the effectiveness and safety of two forms of midazolam prescription; intramuscular (IM) and intravenous (IV). Patients ...
Bhatt, Deepak L.; Lincoff, A. Michael; Gibson, C. Michael; Stone, Gregg W.; McNulty, Steven; Montalescot, Gilles; Kleiman, Neal S.; Goodman, Shaun G.; White, Harvey D.; Mahaffey, Kenneth W.; Pollack, Charles V.; Manoukian, Steven V.; Widimsky, Petr; Chew, Derek P.; Cura, Fernando; Manukov, Ivan; Tousek, Frantisek; Jafar, M. Zubair; Arneja, Jaspal; Skerjanec, Simona; Harrington, Robert A.; Bhatt, D. L.; Harrington, R. A.; Lincoff, A. M.; Pollack, C. V.; Gibson, C. M.; Stone, G. W.; Mahaffey, K. W.; Kleiman, N. S.; Montalescot, G.; White, H. D.; Goodman, S. G.; Greenbaum, A.; Simon, D.; Lee, D.; Feit, F.; Dauerman, H.; Gurbel, P.; Berger, P.; Makkar, R.; Becker, R. C.; Manoukian, S.; Jorgova, J.; Chew, D. P.; Storey, R.; Desmet, W.; Cura, F.; Herrmann, H.; Rizik, D.; DeServi, S.; Huber, K.; Jukema, W. J.; Knopf, W.; Steg, P. G.; Schunkert, H.; Widimsky, P.; Betriu, A.; Aylward, P.; Polonestsky, L.; Lima, V.; Kobulia, B.; Navickas, R.; Gasior, Z.; Vasilieva, E.; Bennett, J. M.; Kraiz, I.; Van de Werf, F.; Faxon, D.; Ohman, E. M.; Tijssen, J. G. P.; Verheugt, F.; Weaver, W. D.; Califf, R. M.; Mehta, C.; Hamm, C. W.; Pepine, C. J.; Ware, J.; Wilson, M.; Gorham, C.; Maran, A.; McNulty, S.; Fasteson, D.; Ryan, G.; Bradsher, J.; Connolly, P.; Mehta, R.; Leonardi, S.; Brennan, M.; Patel, M.; Petersen, J.; Bushnel, C.; Jolicoeur, M.; Chan, M.; Dowd, L.; Skinner, P.; Lawrence, G.; Jordon, M.; Dickerson, S.; Meyer, M.; Hartford, S.; Garcia Escudero, Alejandro; Poy, Carlos; Miceli, Miguel; Pocovi, Antonio; Londero, Hugo; Baccaro, Jorge; Polonetsky, Leonid; Karotkin, Aliaksey; Shubau, Leanid; Maffini, Eduardo; Machado, Bruno; Airton, José; Lima, Valter; Martinez Filho, Eulogio; Herdy, Arthur; Tumelero, Rogerio; Precoma, Dalton; Botelho, Roberto; Saad, Jamil; Jatene, Jose; Vilas-Boas, Fabio; Godinho, Antonio; Perin, Marco; Caramori, Paulo; Castro, Iran; Grigorov, Mladen; Milkov, Plamen; Jorgova, Julia; Georgiev, Svetoslav; Rifai, Nizar; Doganov, Alexander; Petrov, Ivo; Hui, William; Lazzam, Charles; Reeves, Francois; Tanguay, Jean-Francois; Richter, Marek; Klimsa, Zdenek; Padour, Michal; Mrozek, Jan; Branny, Marian; Coufal, Zdenek; Simek, Stanislav; Rozsival, Vladimir; Pleva, Leos; Stasek, Josef; Kala, Petr; Groch, Ladislav; Kocka, Viktor; Shaburishvili, Tamaz; Khintibidze, Irakli; Chapidze, Gulnara; Mamatsashvili, Merab; Mohanan, Padinhare; Jain, Rajesh; Parikh, Keyur; Patel, Tejas; Kumar, Sampath; Mehta, Ashwani; Banker, Darshan; Krishna, Lanka; Gadkari, Milind; Joshi, Hasit; Hiremath, Shirish; Grinius, Virgilijus; Norkiene, Sigute; Petrauskiene, Birute; Michels, Rolf; Tjon, Melvin; de Swart, Hans; de Winter, Robbert; White, Harvey; Devlin, Gerard; Abernethey, Malcolm; Osiev, Alexander; Linev, Kirill; Kalinina, Svetlana; Baum, Svetlana; Kosmachova, Elena; Shogenov, Zaur; Markov, Valentin; Boldueva, Svetlana; Barbarash, Olga; Kostenko, Victor; Vasilieva, Elena; Gruzdev, Aleksey; Lusov, Victor; Dovgalevsky, Pavel; Azarin, Oleg; Chernov, Sergey; Smolenskaya, Olga; Duda, Alexey; Fridrich, Viliam; Hranai, Marian; Studencan, Martin; Kurray, Peter; Bennett, John; Blomerus, Pieter; Disler, Laurence; Engelbrecht, Johannes; Klug, Eric; Routier, Robert; Venter, Tjaart; van der Merwe, Nico; Becker, Anthony; Cha, Kwang-Soo; Lee, Seung-Hwan; Han, Sang-Jin; Youn, Tae Jin; Hur, Seung-Ho; Seo, Hong Seog; Park, Hun-Sik; Rhim, Chong-Yun; Pyun, Wook-Bum; Choe, Hyunmin; Jeong, Myung-Ho; Park, Jong-Seon; Shin, Eak-Kyun; Hernández, Felipe; Figueras, Jaume; Hernández, Rosana; López-Minguez, José Ramón; González Juanatey, José Ramón; Palop, Ramón López; Galeote, Guillermo; Chamnarnphol, Noppadol; Buddhari, Wacin; Sansanayudh, Nakarin; Kuanprasert, Srun; Penny, William; Lui, Charles; Grimmett, Garfield; Srinivasan, Venkatraman; Ariani, Kevin; Khan, Waqor; Blankenship, James; Cannon, Louis; Eisenberg, Steven; McLaurin, Brent; Mahoney, Paul; Greenberg, Jerry; Breall, Jeffrey; Chandna, Harish; Hockstad, Eric; Tolerico, Paul; Kao, John; Shroff, Adhir; Nseir, Georges; Greenbaum, Adam; Cohn, Joel; Gogia, Harinder; Nahhas, Ahed; Istfan, Pierre; Orlow, Steve; Spriggs, Douglas; Sklar, Joel; Paulus, Richard; Cochran, David; Smith, Robert; Ferrier, L. Norman; Scott, J. Christopher; Xenopoulos, Nicholaos; Mulumudi, Mahesh; Hoback, James; Ginete, Wilson; Ballard, William; Stella, Joseph; Voeltz, Michele; Staniloae, Cezar; Eaton, Gregory; Griffin, John; Kumar, Krishna; Ebrahimi, Ramin; O'Shaughnessy, Charles; Lundstrom, Lundstrom; Temizer, Dogan; Tam, Kenneth; Suarez, Jose; Raval, Amish; Kaufman, Jay; Brilakis, Emmanouil; Stillabower, Michael; Quealy, Kathleen; Nunez, Boris; Pow, Thomas; Samuels, Bruce; Argenal, Agustin; Srinivas, Vankeepuram; Rosenthal, Andrew; Tummala, Pradyumna; Myers, Paul; LaMarche, Nelson; Chan, Michael; Bach, Richard; Simon, Daniel; Kettelkamp, Richard; Helmy, Tarek; Schaer, Gary; Kosinski, Edward; Buchbinder, Maurice; Sharma, Mukesh; Goodwin, Mark; Horwitz, Phillip; Mann, J. Tift; Holmes, David; Angiolillo, Dominick; Rao, Sunil; Azrin, Michael; Gammon, Roger; Mavromatis, Kreton; Ahmed, Abdel; Kent, Kenneth; Zughaib, Marcel; Westcott, R. Jeffrey; Jain, Ash; Gruberg, Luis; LeGalley, Thomas
BACKGROUND: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI). METHODS: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been
Background: This study was designed to evaluate the effect of intravenous dexmedetomidine infusion in patients undergoing major abdominal surgery on stress response markers as plasma interleukin-6, cortisol and blood glucose level. It also assessed its effect on recovery profile and postoperative pain. Methods: Thirty ...
Kohli, G.S.; Yadav, S.P.S.; Chowdhry, D.; Mehta, H.C.
Twenty-five patients with head and neck cancer and 25 age-matched normal controls were investigated for serum, immunoglobulin levels (IgA, IgG and IgM). The levels of all the three immunoglobulins in the patients were significantly higher than controls, the rise in IgA being more than that of IgG or IgM. The ratios of IgA/IgG and IgA/IgM were also higher than normal. The immunoglobulin levels showed a progressive rise with the advance in stage of the tumour. A fall in the immunoglobulin levels, as well as in the ratios of IgA/IgG and IgA/IgM, was noted following radiotherapy though the levels were still higher than controls. The range of increase in immunoglobulins appears to be a satisfactory prognostic tool, and a fall after radiotherapy appears to be related to the effectiveness of treatment. (author). 3 tables, 11 refs
Muchtar, Eli; Magen, Hila; Itchaki, Gilad; Cohen, Amos; Rosenfeld, Ra'ama; Shochat, Tzippy; Kornowski, Ran; Iakobishvili, Zaza; Raanani, Pia
Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens. Copyright © 2015 Elsevier Ltd. All rights reserved.
Khodadoust, Michael S; Olsson, Niclas; Wagar, Lisa E; Haabeth, Ole A W; Chen, Binbin; Swaminathan, Kavya; Rawson, Keith; Liu, Chih Long; Steiner, David; Lund, Peder; Rao, Samhita; Zhang, Lichao; Marceau, Caleb; Stehr, Henning; Newman, Aaron M; Czerwinski, Debra K; Carlton, Victoria E H; Moorhead, Martin; Faham, Malek; Kohrt, Holbrook E; Carette, Jan; Green, Michael R; Davis, Mark M; Levy, Ronald; Elias, Joshua E; Alizadeh, Ash A
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4 + T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.
Rudis, Maria I; Touchette, Daniel R; Swadron, Stuart P; Chiu, Amy P; Orlinsky, Michael
Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse
Gaut, P L; Carron, W C; Ching, W T; Meyer, R D
The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.
medetomidine for total intravenous anaesthesia were evaluated in six sahel goats. The goats were administered a combination of ketamine (5mg/kg) and medetomidine (0.01mg/kg) intravenously. Baseline measurements of heart rate, respiratory ...
Wu, Chuang; Hou, Nan; Piao, Xianyu; Liu, Shuai; Cai, Pengfei; Xiao, Yan; Chen, Qijun
Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum. PMID:26299686
Georgakopoulos, Thanae; Tatford, Owen C; Gurevich, Vladimir; Bertolini, Joseph
Aggregates in human immunoglobulin (Ig) products can develop due to employed manufacturing, formulation and storage conditions and can cause adverse reactions in patients. The test for anti-complementary activity (ACA) recommended by the European Pharmacopoeia (EP) is insensitive, variable and time consuming. We have optimised a commercial assay for the detection and quantitation of C1q binding aggregates in intravenous and intramuscular IgG preparations. The generation of C4d, iC3b and SC5b-9 induced by aggregates in vitro was measured by enzyme-linked immunosorbent assays (ELISA). In establishing the sensitivity of the C1q aggregate binding assay to detect IgG aggregates in comparison to turbidity and ACA, pure IgG at neutral and acidic pH was heated for various lengths of time to generate varying amounts of aggregates. The level of C1q binding aggregates was 7 fold greater in intramuscular samples. These aggregates were capable of activating complement in vitro and correlated with an increase in ACA. C1q aggregate binding was apparent before any quantifiable turbidity and ACA in the heat-treated samples. Furthermore, the C1q binding assay could discriminate between different levels of aggregates where ACA had reached a plateau. C1q aggregate binding is a sensitive, convenient, specific and robust means of detecting aggregates with a propensity for complement activation. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
Lozano, Natalia A; Lozano, Alejandro; Sasia, Laura V; Saranz, Ricardo J; Agresta, María Fernanda; del Pilar Bovina Martijena, María; Ianiero, Luciano; Grenat, Andrés R
Primary immunodeficiencies (PID) are low-prevalence diseases. There are warning signs that may raise clinical suspicion. The objectives of this study were to describe the clinical characteristics and warning signs of patients with PID and to compare the clinical differences between selective immunoglobulin A (IgA) deficiency and other PIDs. Eighty-nine patients were studied; their median age at the time of diagnosis was 6 years old (4.08-11.67). Fifty-three (59.5%) patients were male. Fifty-four (60.7%) patients had selective IgA deficiency, and 35 (39.3%) had other PIDs. The main clinical manifestations were rhinopharyngitis in 65 (73.03%) patients and atopy in 39 (43.82%). Twenty- four (26.97%) patients showed warning signs, and none had selective IgA deficiency. Patients with other PIDs had a higher incidence of lower respiratory tract infection, sepsis, skin infections, mucocutaneous candidiasis, dental alterations, cardiovascular malformations, angioedema, hospitalizations and death. Ten (28.57%) patients received intravenous gammaglobulin, 15 (42.85%) antibiotic prophylaxis, and 2 (2.24%) antifungal prophylaxis.
Full Text Available Shiga toxins (Stxs are involved in the development of severe systemic complications associated with enterohemorrhagic Escherichia coli (EHEC infection. Various neutralizing agents against Stxs are under investigation for management of EHEC infection. In this study, we immunized chickens with formalin-inactivated Stx-1 or Stx-2, and obtained immunoglobulin Y (IgY from the egg yolk. Anti-Stx-1 IgY and anti-Stx-2 IgY recognized the corresponding Stx A subunit and polymeric but not monomeric B subunit. Anti-Stx-1 IgY and anti-Stx-2 IgY suppressed the cytotoxicity of Stx-1 and Stx-2 to HeLa 229 cells, without cross-suppressive activity. The suppressive activity of these IgY was abrogated by pre-incubation with the corresponding recombinant B subunit, which suggests that the antibodies directed to the polymeric B subunits were predominantly involved in the suppression. In vivo, the intraperitoneal or intravenous administration of these IgY rescued mice from death caused by intraperitoneal injection of the corresponding toxin at a lethal dose. Moreover, oral administration of anti-Stx-2 IgY reduced the mortality of mice infected intestinally with EHEC O157:H7. Our results therefore suggest that anti-Stx IgY antibodies may be considered as preventive agents for Stx-mediated diseases in EHEC infection.
Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S
Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours
Full Text Available Rabies is a viral disease with the high rate of mortality, which is non-curable after presenting clinical signs weather in humans or animals. Persons who are bitten by suspicious animals can be protected from rabies, in case of early referring to the health care preventive centers. However, the rate of durability and safety are questionable among those received immunoglobulin and vaccine. Here, it was reported a 57 year-old woman who was bitten by a jackal and died, despite of receiving immunoglobulin and rabies vaccine.
Krakauer, M; Schaldemose Nielsen, H; Jensen, J
OBJECTIVE: The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. MATERIAL AND METHODS: Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients with cli......OBJECTIVE: The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. MATERIAL AND METHODS: Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients...
Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.
Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.
Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha
Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear I...
Popović, M; Hrzenjak, T; Grdisa, M; Vuković, S
1. From the biologically active extract (G-90) isolated from the tissue homogenate of Eisenia foetida immunoglobulin-like structures were isolated and named G-90/4. 2. G-90/4 in nanogram concentrations stimulated cell proliferation more than did the original G-90. It lyses cells in microgram concentrations. 3. G-90/4 acts as an adhesion molecule between the receptors of adjacent cells. 4. The increase in proliferative activity was accompanied by the elevation of cytoplasmic protein containing tyrosine. 5. Immunohistochemical analyses confirm immunoglobulin-like transmembrane structures in the connective and muscular tissues of E. foetida.
Creagh, F. M.; Stone, T.; Stephenson, T. P.; Lazarus, J. H.
A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages o...
Cancio, Leopoldo C; Cuenca, Phillip B; Walker, Stephen C; Shepherd, John M
Total intravenous anesthesia (TIVA) is frequently used for major operations requiring general anesthesia in critically ill burn patients. We reviewed our experience with this approach. Methods: During a 22-month period, 547 major burn surgeries were performed in this center’s operating room and were staffed by full-time burn anesthesiologists. The records of all 123 TIVA cases were reviewed; 112 records were complete and were included. For comparison, 75 cases were selected at random from a t...
Zeman, H.D.; Siddons, D.P.
The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth
Ghassan S. A. Salama
Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.
Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg) but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin (light chain specific... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system. (a) Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific... Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fd fragment specific) immunological test system is a device that consists of...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulins A, G, M, D, and E immunological... Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the...
Summary: Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port ...
Full Text Available Neonatal mortality is very high in farm animals (~10% and disease resistance is greatly influenced by an adequate passive immunisation just after birth. In piglets, foals, calves and lambs, the intestinal absorption of immunoglobulins from their mother's colostrum occurs mainly by a non-specific endocytosis of macromolecules, but the details of the absorption process, and the mechanisms regulating its cessation after 1–2 days of colostrum exposure, remain poorly understood. In both normal and 'compromised' (premature, growth-retarded, hypoxic, lethargic newborn farm animals, the intestinal capacity to absorb macromolecules is influenced by both diet- and animal-related factors. Thus, macromolecule uptake is severely reduced in response to premature birth and when macromolecules are to be absorbed from diets other than species-specific colostrum. On the other hand, fetal growth retardation, in vitro embryo production, or a stressful birth process are unlikely to reduce the ability of the intestine to absorb immunoglobulins from colostrum. More knowledge about the diet- and animal-related factors affecting intestinal immunoglobulin uptake will improve the clinical care of 'compromised' newborn farm animals. The present text gives a brief introduction to the process of intestinal immunoglobulin absorption in large farm animals and describe some recent results from the author's own studies in pigs, calves and lambs.
Martel, Cyril Jean-Marie; Aasted, Bent
This study describes easy purification methods for mink IgG, IgA and IgM immunoglobulins. IgG and IgM were purified from normal mink serum, while IgA was purified from mink bile from healthy animals. By SDS-polyacrylamid-gel-electrophoresis (SDS-PAGE) and immunoblotting under reducing conditions...
Objective: To elute placental bound immunoglobulin G (IgG) in situ. Design: Laboratory based experimentation. Setting: Biological Sciences Department, The University of Newcastle Australia and the Department of Biochemistry, University of Nairobi, Kenya. Subjects: Twelve pregnant ewes 10 to 15 days before the onset of ...
Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port Harcourt, ...
Thomson, Leonor; Tenopoulou, Margarita; Lightfoot, Richard; Tsika, Epida; Parastatidis, Ioannis; Martinez, Marissa; Greco, Todd M.; Doulias, Paschalis-Thomas; Wu, Yuping; Tang, W. H. Wilson; Hazen, Stanley L.; Ischiropoulos, Harry
Background Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine nitrated proteins, a footprint of oxygen and nitrogen derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of coronary artery disease (CAD) subjects. However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. Methods and Results Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of CAD subjects. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in CAD patients (n=374) and subjects without CAD (non CAD controls, n=313). A ten-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in the CAD subjects (3.75 ± 1.8 μg antibody Eq/mL plasma vs. 0.36 ± 0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. Conclusions The results of this cross sectional study suggest that post-translational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neoepitopes for elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD. PMID:23081989
Lomholt, JA; Kilian, Mogens
The purpose of this study was to determine the occurrence and nature of immunoglobulin A1 (IgA1) protease activity in members of the genus Gemella and related taxa. Among a total of 22 Gemella strains belonging to the four species Gemella haemolysans, Gemella morbillorum, Gemella sanguinis...
Kolenko, Petr; Dohnálek, Jan; Štouračová, Renata; Skálová, Tereza; Tishchenko, Galina; Dušková, Jarmila; Hašek, Jindřich
Roč. 12, č. 2 (2005), s. 146-147 ISSN 1211-5894. [Colloquium of Crystallographic Society : Structure. Třešť, 20.06.2005-23.06.2005] R&D Projects: GA MŠk(CZ) 1K05008 Keywords : immunoglobulin * x-ray crystallography * structure determination Subject RIV: EB - Genetics ; Molecular Biology
Servant, P.; Borgard, J.P.
Study on the influence of irradiation upon rabbit immunoglobulins is developed. It is tried to check if the observed delay, after cephalic irradiation, in specified antibody response of injected antigen, could be in relation with a transient hypoimmunoglobulinemia in these same animals [fr
Selman, Maurice Henricus Johannes
Immunoglobulin G (IgG) represents the most abundant antibody class in the human circulation. IgG consists of two heavy chains and two light chains. Parts of the heavy chains, together with the light chains, form two fragment antigen binding (Fab) moieties, whilst the remainders of the two heavy
de Jager, AEJ; van der Hoeven, JH
Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually
Servonnet, Aurélie; Bouvier, François; Garcia Hejl, Carine; Sanmartin, Nancy; Renard, Christophe
Amyloidosis results from extra-cellular deposition of proteins which interfere with tissue function. We report the case of a patient with pathological heart involvement which is caused by immunoglobulin D amyloidosis, and review current data on the amyloidois diagnosis and management.
van der Waaij, Laurens A.; Kroese, Frans G. M.; Visser, Annie; Nelis, Gerardus F.; Westerveld, Bram D.; Jansen, Peter L. M.; Hunter, John O.
OBJECTIVE: An inappropriate mucosal immune response to the commensal bacterial flora may play a role in the pathogenesis of inflammatory bowel disease (IBD). In this study we determined the percentage of immunoglobulin-coated bacteria in the stools of patients and controls. METHODS: Faecal samples
Al Hadidi, Samer; Katato, Khalil; Bachuwa, Ghassan
Immunoglobulin D multiple myeloma is a rare type of multiple myeloma that usually presents as bone pain, fatigue, or weight loss. We report a case of immunoglobulin D multiple myeloma in a 53-year-old Caucasian male patient with previous medical history of anaplastic oligodendroglioma status post-surgical resection who was evaluated for back pain while mowing the lawn. His physical examination showed tenderness over the lower thoracic vertebrae with no sensory or motor impairment. Initial lab investigations showed normocytic anemia and hypercalcemia with low parathyroid hormone. Magnetic resonance imaging of thoracic spine with and without contrast showed acute pathological fracture of the T12 vertebral body with enhancing soft tissue which extended into the left ventral epidural space and left T11-T12 neural foramen. Serum protein electrophoresis showed abnormal protein band in the gamma globulin. Free light chain assay showed serum free kappa which was elevated at 3,090.0 mg/L (reference range 3.3-19.4 mg/L). Immunoglobulin D was elevated at 566.0 mg/dL (reference range immunoglobulin D multiple myeloma urge clinicians to offer their patients new treatment options especially as of the earlier presentation of this subtype of multiple myeloma and the previous reports of worse prognosis.
Ziegler, Leslie; Yang, Lili; Joo, Kye il; Yang, Haiguang; Baltimore, David; Wang, Pin
Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient method to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and in vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral surface. This engineered vector could specifically bind to cells expressing surface immunoglobulin recognizing CD20 (alphaCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing alphaCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin- specific cells to deliver a therapeutic effect. Such targeting lentivectors also could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology.
Background: No single organic cause has been found for schizophrenia and its management has been difficult. More so, there are few data on the immune parameters of Nigerian schizophrenic patients on drug treatment and those that are not on treatment. Methodology: This study determines the levels of immunoglobulin
Apart from antiphospholipid- and thyroid- autoantibodies which were reported as underlying causes of recurrent pregnancy loss, specific IgG to patermal MHC and Rh was proposed. This raises the possibility of other classes of immunoglobulin in recurrent abortion. Twenty-four pregnant women with recurrent abortion ...
all assays were calculated as a percentage of the mean of. TABLE I. RESULTS OF IMMUNOGLOBULIN ASSAYS OF tOO WHITE, tOO ASIATIC AND 100 BANTU DONORS, EXPRESSED AS A. PERCENTAGE OF A CONTROL SERUM. Parameter. Range. Mean. Variance. Standard deviation. CoefI. of variation.
... stained positive for CD68. Type III reaction consisted of a discrete epithelioid granuloma without wellformed grains. IgG, IgM and C3 were found on the surface of the grain and the hyphae . Keywords: Madurella mycetomatis lesion, cell phenotypes, immunoglobulins, complement. Sudanese Journal of Dermatology Vol.
Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.
Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,
Gambón-Deza, F; Sánchez-Espinel, C; Magadán-Mompó, S
Immunoglobulins loci in mammals are well known to be organized within a translocon, however their origin remains unresolved. Four of the five classes of immunoglobulins described in humans and rodents (immunoglobulins M, G, E and A-IgM, IgG, IgE and IgA) were found in marsupials and monotremes (immunoglobulin D-IgD was not found) thus showing that the genomic structure of antibodies in mammals has remained constant since its origin. We have recently described the genomic organization of the immunoglobulin heavy chain locus in reptiles (IGHM, IGHD and IGHY). These data and the characterization of the IGH locus in platypus (Ornithorhynchus anatinus), allow us to elucidate the changes that took place in this genomic region during evolution from reptile to mammal. Thus, by using available genome data, we were able to detect that platypus IGH locus contains reptilian and mammalian genes. Besides having an IGHD that is very similar to the one in reptiles and an IGHY, they also present the mammal specific antibody genes IGHG and IGHE, in addition to IGHA. We also detected a pseudogene that originated by recombination between the IGHD and the IGHM (similar to the IGHD2 found in Eublepharis macularius). The analysis of the IGH locus in platypus shows that IGHY was duplicated, firstly by evolving into IGHE and then into IGHG. The IGHA of the platypus has a complex origin, and probably arose by a process of recombination between the IGHM and the IGHY. We detected about 44 VH genes (25 were already described), most of which comprise a single group. When we compared these VH genes with those described in Anolis carolinensis, we find that there is an evolutionary relationship between the VH genes of platypus and the reptilian Group III genes. These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families.
Full Text Available Understanding how class switch recombination (CSR is regulated to produce immunoglobulin E (IgE has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2, which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.
Develioglu, Omer Necati; Kucur, Mine; Ipek, Havva Duru; Celebi, Saban; Can, Gunay; Kulekci, Mehmet
To investigate the effects of Ramadan fasting on serum concentrations of immunoglobulin (Ig)G and IgM, and salivary IgA concentrations. Blood and saliva samples were collected one week before and during the last week of Ramadan from healthy male volunteers. Albumin, total lymphocyte count, electrolytes, and IgG and IgM concentrations were determined in serum; salivary IgA concentrations were measured. Anthropometric measurements were also recorded. Samples were collected from 35 subjects (mean age 35.86 years, range 20-59 years). Weight, body mass index, albumin levels and the nutritional risk index decreased significantly during Ramadan fasting compared with before fasting. In addition, Na(+) and Cl(-) electrolyte levels were significantly decreased during Ramadan. Serum IgG concentrations decreased significantly during Ramadan compared with before fasting, but were still within the normal range. Salivary IgA concentrations also decreased significantly, whereas serum IgM levels did not change. Lymphocyte numbers increased significantly, but there was no correlation between Ig levels and lymphocyte count. Ramadan fasting did not result in severe immunological disturbances.
Full Text Available Naturally acquired immunity against invasive pneumococcal disease (IPD is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG, representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule.
Full Text Available The timely supply of newborn calves with optimal quantities of colostrum has a key role in the process of immune protection in the early phase of their lives. Passively acquired antibodies can protect the digestive organs from infection caused by E.coli bacteria, and it seems also from the appearance of diseases of the respiratory tract. These examinations were performed on a cattle farm where bronchopneumonia was one of the most significant health problems, and a group of 39 calves were selected for the investigations. The calves were fed with their mothers’ colostrum after birth, and then with collective milk. Immunoglobulin concentration was determined in blood samples taken during the postcolostral period, with the method using zinc-sulphate. At the age of 40 days, the calves were administered a polyvalent inactivated vaccine, and revaccinated 20 days after that (Vibak, Veterinary Department Subotica. In 74.34% calves, the immunoglobulin G concentration ranged from 26 to 40 g/l. In 25.66% calves, the immunoglobulin concentration was lower, from 8 to 25 g/l. The calves found to have a lower concentration of immunoglobulin in blood contracted bronchopneumonia more frequently, and the outcome of the disease in some cases was mortality, even.
Budde, Ilona Kleine; de Heer, Pleuni G.; Natter, Susanne; Mahler, Vera; van der Zee, Jaring S.; Valenta, Rudolf; Aalberse, Rob C.
It has been reported that serum immunoglobulin E (IgE) from certain atopic patients can sensitize basophils to release histamine in response to IgE-dependent histamine-releasing factors (HRFs). It has also been shown that patients suffering from severe forms of atopy may contain IgE autoantibodies.
Shetty, P.C.; Krasicky, G.A.; Sharma, R.P.; Vemuri, B.R.; Burke, M.M.
Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. The authors present the results of their experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population
Sarker, Shafiqul A.; Pant, Neha; Juneja, Lekh R.; Hammarström, Lennart
The role of specific immunoglobulins at mucosal sites in imparting protection against disease, such as rotavirus-associated diarrhoea, is well-established. Oral immunoglobulin therapy with egg yolk-derived antirotavirus immunoglobulins has previously been shown to achieve moderate therapeutic effect in diarrhoea due to rotavirus in a clinical trial. Here, data on the therapeutic potential of the same immunoglobulin preparation in an infant mouse model of rotavirus-induced diarrhoea is presented. The use of an animal model has allowed therapy to be evaluated with higher doses of immunoglobulins and has suggested that an improved therapeutic effect can be achieved by increasing the dose in the clinical setting. PMID:18402190
Full Text Available Objective: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Method: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. Results: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions, 60,30% in oncology (28,127 infusions, 46,50% in rheumatology (1,950 infusions and 1.8% in oncopediatrics (139 infusions. 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%, errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. Conclusions: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies.
Edelman, K; Valenzuela, J E
Parenteral alimentation, including intravenous fat, is sometimes used in the treatment of patients with pancreatitis, although the effect of intravenous fat on human pancreatic secretion has not been systematically studied. Intravenous fat, however, has been shown to stimulate pancreatic protein secretion in the dog. The purpose of these studies was to clarify the effect of intravenous fat on human pancreatic secretion. Pancreatic secretion was assessed by measurement of enzymes and bicarbonate in duodenal aspirate collected via a double-lumen tube from 6 healthy volunteers. Four studies were randomly conducted on different days. On day 1, graded concentrations of Intralipid (5%, 10%, and 20%) were given intravenously for 1 h each, while secretin (8.2 pmol . kg-1 . h-1) was given as a background. On day 2, the same doses of Intralipid were infused intravenously without secretin. On day 3, the same doses of Intralipid were perfused into the intestine, and, finally, on day 4, 20% Intralipid was given by intestinal infusion for 2 h while 10% Intralipid was infused intravenously during the second hour. Significant stimulation of enzyme secretion was observed only during the infusion of fat into the intestine, not after intravenous infusion at any concentration. Pancreatic enzyme secretion, stimulated by intraintestinal fat, was not significantly modified by simultaneous intravenous lipid infusion. We conclude that since intravenous fat does not stimulate pancreatic secretion, its use in conditions where pancreatic stimulation is undesirable appears safe.
Creagh, F. M.; Stone, T.; Stephenson, T. P.; Lazarus, J. H.
A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages of the illness. Images Figure 1 Figure 2 PMID:3983053