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Autoimmune Reactions (autoimmune + reaction)
Selected AbstractsCpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling miceINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2002T. Hayashi Summary. We reported previously that reovirus type-2 (Reo-2) triggers T-helper (Th) 1-mediated autoimmune insulitis resulting in temporal impaired glucose tolerance (IGT) approximately 10 days post infection (d.p.i) in suckling DBA/1 mice. We hypothesized that CpG motifs in bacteria may enhance virus-induced insulitis through its content of unmethylated CpG motifs. In the infected mice, the intraperitoneal treatment of synthetic 20-base oligodeoxynucleotides with CpG motifs (CpG ODN) caused increase in cumulative incidence of insulitis with IGT, increased serum interferon (IFN)-, concentration, and high frequency of autoantibody against pancreatic islet cells, compared to the infected mice without CpG ODN at 17 d.p.i. Also CD4+ and CD8+ lymphocytes infiltrated in and/or around pancreatic islets in the CpG ODN-treated mice. This evidence suggests that CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokines especially IFN-,. [source] AIDS dementia complex and Hashimoto encephalopathy in a senescent womanINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 12 2007Robert Waltereit Abstract AIDS dementia complex is one of the specific infectious dementias, which is rarely seen in senescent (>75 years of age) subjects. Hashimoto encephalopathy has been described as the cause of several neurological and psychiatric syndromes including dementia. The proposed pathophysiological mechanism is an autoimmune reaction to shared, thyroid gland and CNS epitopes with subsequent cerebral dysfunction. We report here the first case of a patient who fulfils both, the criteria for AIDS dementia complex and Hashimoto encephalopathy, yet being unresponsive to steroid therapy. Diagnostic and therapeutic implications are discussed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Sustained response to combination therapy in a patient with chronic hepatitis C and thrombocytopenia secondary to , -interferonJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2000Manuel Jiménez-Sáenz Abstract Recent data suggest that hepatitis C viral (HCV) infection may induce a significant autoimmune reaction to platelets, but the mechanism is unknown. Many patients with chronic hepatitis C, in fact, have high levels of platelet-associated immunoglobulin G (PAIgG) and HCV-RNA is present in the platelets of 100% of those patients with thrombocytopenia and high PAIgG levels. Hepatitis C virus infection has been associated with the development of thrombocytopenic purpura, sometimes triggered during interferon (IFN) therapy. In such cases, the treatment of the underlying disease is a difficult problem to solve. We report the case of a patient with chronic hepatitis C, who developed life-threatening thrombocytopenic purpura after a prolonged course of IFN-,2b over a 4-year period. Treatment with anti-immunoglobulin gammaglobulin (Polyglobin®; Química Farmaceutica Bayer, Barcelona, Spain) had a transient effect on the platelet count, but prolonged therapy with prednisone was necessary for definitive relief of the haematological complication. Two years later, the patient was treated with combined therapy, including ribavirin (1200 mg/day) and IFN-,2b (5 mU, t.i.w.) for 12 months. This therapy induced a sustained response, both biochemical and virological, without haematological complications. This observation suggests that ribavirin may be of benefit in the treatment of immune-mediated thrombocytopenia in patients with chronic hepatitis C, preventing the harmful effect of IFN-, but also allowing both drugs to be combined so as to increase the probability of sustained remission of the liver disease. [source] Progressive circumscribed sclerosis , a novel side-effect of immunotherapy with aluminium-adsorbed allergen extractsALLERGY, Issue 6 2009El Shabrawi-Caelen In the susceptible patient aluminum may trigger an autoimmune reaction with progressive sclerosis as the key clinical feature. [source] HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccinationARTHRITIS & RHEUMATISM, Issue 4 2009Robert Ball Objective To investigate whether persons with treatment-resistant Lyme arthritis,associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen. Methods Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA,DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed. Results Twenty-seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment-resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3-2.1), 1.6 (95% CI 0.5,4.4), and 1.75 (95% CI 0.6,5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5,5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2,2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1,0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%). Conclusion Treatment-resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases. [source] Behçet's disease and vitiligo in two brothers: coincidence or association?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 8 2009M. Borlu Summary Behçet's disease (BD) and vitiligo are disorders with unknown aetiology. We report on two brothers with ocular Behcet's disease who had advanced unilateral ophthalmic symptoms associated with vitiligo. The two brothers had recurrent oral and genital ulceration, uveitis and white patches on their skin. The most probable hypothesis for the aetiology of BD is that of an autoimmune reaction in genetically predisposed individuals, with vasculitis as the main pathological hallmark. Despite many years of research, the specific causes of vitiligo remain obscure, and the most advanced aetiological hypothesis remains that of autoimmunity. To our knowledge, this is the first reported case within the literature of BD associated with vitiligo. The existence of the two different disorders is noteworthy as they were observed in two brothers during the same period in their lives, with very similar clinical observations. [source] ,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] Mucosal Production of Antigastric Autoantibodies in Helicobacter pylori GastritisHELICOBACTER, Issue 3 2000Gerhard Faller Background. Apart form bacterial virulence factors of Helicobacter pylori, certain host factors influence the pathogenesis of H. pylori gastritis. In particular, antigastric autoantibodies that are detectable in the sera of a substantial proportion of H. pylori were shown to correlate with the development of gastric atrophy. The aim of this study was to analyze the possible antigastric autoimmune response in H. pylori gastritis at the site where the action is, i.e., in the gastric mucosa. Material and Methods. Gastric biopsy specimens from antrum and corpus mucosa of 24 H. pylori,infected and of 33 noninfected patients were cultured for 3 days, and tissue culture supernatants were analyzed for the amount of locally produced IgA and IgG. Antigastric autoantibodies were screened in the sera and in the supernatants by means of immunohistochemistry. Results. The infected patients had significantly higher concentrations of locally produced IgA, whereas the IgG concentrations were virtually the same in infected and noninfected patients. IgG or IgA antigastric autoantibodies, or both, were detectable only in the sera (38%) and supernatants (17%) of infected patients. Interestingly, the patient with the strongest local autoimmune response showed body-predominant H. pylori gastritis, with destruction of gastric glands and atrophy of the body mucosa. Conclusions. These results demonstrate that antigastric autoimmune reactions are detectable at the site of the disease and might be relevant for the pathogenesis of gastric mucosa atrophy in H. pylori gastritis. [source] Monocytes in the rat: Phenotype and function during acute allograft rejectionIMMUNOLOGICAL REVIEWS, Issue 1 2001Birte Steiniger Summary: Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through post-capillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-vascularized allografts and chronic allograft rejection. It is very likely that they also contribute to acute allograft destruction. So far it has been impossible to distinguish the function of monocytes from that of macrophages, because cell phenotypes and their alterations upon activation are ill-defined. We have thus begun to characterize the ex vivo phenotype and function of rat monocytes in the normal state and during renal allograft rejection. Monocytes are recovered from both the central and the marginal blood pool by perfusing either the recipient's circulation or the allograft vasculature. Rat monocytes have a unique surface phenotype. During allograft rejection or after infusion of interferon-, they up-regulate class II MHC molecules, CD161 (NKR-P1A), CD62L and CD8, while CD4 and CD43 are down-modulated. Activated perfusate monocytes exert increased in vitro cytotoxicity against tumour targets, which differs from that of NK cells. We speculate that activated monocytes contribute to kidney allograft destruction by directly damaging endothelial cells or by promoting intravascular coagulation. [source] Popliteal lymph node assay: facts and perspectivesJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005Guillaume Ravel Abstract The popliteal lymph node assay (PLNA) derives from the hypothesis that some supposedly immunemediated adverse effects induced by certain pharmaceuticals involve a mechanism resembling a graft-versus-host reaction. The injection of many but not all of these compounds into the footpad of mice or rats produces an increase in the weight and/or cellularity of the popliteal lymph node in the treated limb (direct PLNA). Some of the compounds known to cause these adverse effects in humans, however, failed to induce a positive PLNA response, leading to refinements of the technique to include pretreatment with enzyme inducers, depletion of CD4+ T cells or additional endpoints such as histological examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative approaches have been used to improve further the predictability of the assay. In the secondary PLNA, the test compound is injected twice in order to illicit a greater secondary response, thus suggesting a memory-specific T cell response. In the adoptive PLNA, popliteal lymph node cells from treated mice are injected into the footpad of naive mice; a marked response to a subsequent footpad challenge demonstrates the involvement of T cells. Finally, the reporter antigens TNP-Ficoll and TNP-ovalbumin are used to differentiate compounds that induce responses involving neo-antigen help or co-stimulatory signals (modified PLNA). The PLNA is increasingly considered as a tool for detection of the potential to induce both sensitization and autoimmune reactions. A major current limitation is validation. A small inter-laboratory validation study of the direct PLNA found consistent results. No such study has been performed using an alternative protocol. Other issues include selection of the optimal protocol for an improved prediction of sensitization vs autoimmunity, and the elimination of false-positive responses due to primary irritation. Finally, a better understanding of underlying mechanisms is essential to determine the most relevant endpoints. The confusion resulting from use of the PLNA to predict autoimmune-like reactions as well as sensitization should be clarified. Interestingly, most drugs that were positive in the direct PLNA are also known to cause drug hypersensitivity syndrome in treated patients. This observation is expected to open new avenues of research. Copyright © 2005 John Wiley & Sons, Ltd. [source] Hepatitis C virus-related extra-hepatic disease , aetiopathogenesis and managementALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2004J. Medina Summary Hepatitis C virus infection is often associated with extra-hepatic manifestations, secondary to the elicitation of autoimmune reactions, generalized deposition of immune complexes and lymphoproliferative disorders. The most clearly established associations are those linking chronic hepatitis C with mixed cryoglobulinaemia (and the related glomerulonephritis and cutaneous vasculitis), as well as with the presence of autoantibodies. Less well-documented disorders include non-Hodgkin's lymphoma, thrombocytopenia, sialadenitis, thyroid disease, lichen planus, porphyria cutanea tarda, rheumatoid disorders and neurological disorders. Extra-hepatic manifestations are most frequent in patients of female sex, advanced age, long-lasting infection and cirrhosis. Optimal treatment strategies should be based on the predominant manifestation of the disease. In the case of autoimmune disorders not clearly attributable to the viral infection, corticosteroids may be the most effective option. Interferon-, alone or in combination with ribavirin may be indicated for those disorders related to immune complex deposition, such as mixed cryoglobulinaemia, although relapses of extra-hepatic signs often occur on discontinuation of treatment. In some cases, interferon-, may induce or exacerbate some extra-hepatic manifestations. [source] Annotation: PANDAS: a model for human autoimmune diseaseTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 3 2005Susan E. Swedo Background:, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated neurologic findings including adventitious movements, hyperactivity and emotional lability. Methods:, Inspired by observations of similar symptoms in children with Sydenham's chorea, a search was undertaken for clinical and laboratory evidence in support of the new syndrome. Results:, Consistent and predictable clinical findings have been described in a large case series. Magnetic resonance imaging has supported the postulated pathobiology of the syndrome with evidence of inflammatory changes in basal ganglia. Antibasal ganglia antibodies have been found in some acute cases, mimicking streptococcal antigen epitopes. Conclusions:, While PANDAS remains a controversial diagnostic concept, it has stimulated new research endeavors into the possible links between bacterial pathogens, autoimmune reactions, and neuropsychiatric symptoms. [source] Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis CAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009C. Rigamonti We previously reported that autoantibodies against cytochrome P4502E1 (CYP2E1) are frequent in patients with chronic hepatitis C. As autoimmune reactions are increasingly detected after orthotopic liver transplantation (OLT), this study investigates prevalence and significance of anti-CYP2E1 autoantibodies in 46 patients with post-OLT recurrent hepatitis C. IgG against recombinant human CYP2E1 above the control threshold was detected in 19 out 46 (41%) sera collected immediately before OLT and in 15 out 46 (33%) sera collected at the time of the 12 months follow-up liver biopsy. Although anti-CYP2E1 reactivity was not modified by OLT, the patients with persistently elevated anti-CYP2E1 IgG (n = 12; 26%) showed significantly higher prevalence of recurrent hepatitis with severe necroinflammation and fibrosis than those persistently negative or positive only either before or after OLT. Moreover, the probability of developing severe necroinflammation was significantly higher in persistently anti-CYP2E1-positive subjects. Multivariate regression and Cox analysis confirmed that the persistence of anti-CYP2E1 IgG, together with a history of acute cellular rejection and donor age >50 years, was an independent risk factor for developing recurrent hepatitis C with severe necroinflammation. We propose that autoimmune reactions involving CYP2E1 might contribute to hepatic damage in a subgroup of transplanted patients with recurrent hepatitis C. [source] The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation,BIOESSAYS, Issue 2 2006Michal Pearl-Yafe The exact process that leads to the eruption of autoimmune reactions against , cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of , cell injury is controversial and points to possibly important roles for the perforin,granzyme, Fas,Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of , cells to FasL-mediated apoptosis, the conditions that underlie this , cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of ,-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211,222, 2006. © 2006 Wiley periodicals, Inc. [source] Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its ,-receptorACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 10 2007Joseph Wickham Jr The interleukin-7 (IL-7) signaling pathway plays an essential role in the development, proliferation and homeostasis of T and B cells in cell-mediated immunity. Understimulation and overstimulation of the IL-7 signaling pathway leads to severe combined immunodeficiency, autoimmune reactions, heart disease and cancers. Stimulation of the IL-7 pathway begins with IL-7 binding to its ,-receptor, IL-7R,. Protein crystals of unglycosylated and glycosylated complexes of human IL-7,IL-7R, extracellular domain (ECD) obtained using a surface entropy-reduction approach diffract to 2.7 and 3.0,Å, respectively. Anomalous dispersion methods will be used to solve the unglycosylated IL-7,IL-7R, ECD complex structure and this unglycosylated structure will then serve as a model in molecular-replacement attempts to solve the structure of the glycosylated IL-7,,-receptor complex. [source] Is AZOOR an autoimmune disease?ACTA OPHTHALMOLOGICA, Issue 2007SF SEIDOVA Purpose: Acute zonal occult outer retinopathy (AZOOR) is one of the "white dot syndromes" a clinically heterogeneous group of inflammatory chorioretinopathies. The etiology is not yet clear. Methods: We present a 50 years female patient with a prior history of migraine. She experienced progressive visual loss and visual field defects in the last 3 years. Preceding each episode she experienced blue flickering photopsias. Results: Visual acuity was 0,3 in the right eye and 0,6 in the left eye. Biomicroscopy showed a normal anterior segment, fundus exam revealed pigment epithelial atrophy more pronounced in the worse eye. Electrophysiology showed a marked reduction in the photopic ERG in the more affected eye. MRI demonstrated multiple white matter lesions including a corpus callosum location. Lumbar puncture showed oligoclonal bands. Further tests demonstrated hearing impairment. Therapy was instituted during the three years course of the disease with steroids, immune suppressants and plasmapheresis with visual loss being progressive. New photopsia is currently present. Conclusions: The etiology of AZOOR remains unclear. With our patient being one of the few described in the literature with concomitant multiple sclerosis, the question remains on whether there is an underlying common process of inflammatory autoimmune reactions. Whether treatment is possible, remains to be evaluated. [source] | |||||||||||||||||||||||||