Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disturbances in immune interferon (IFN gamma) activity have been implicated in the development of human systemic lupus erythematosus (SLE) and the spontaneous disease sustained by autoimmune-prone mice. We therefore investigated the cellular basis for IFN gamma production in MRL-Ipr/Ipr mice and examined the relationship between synthesis of interleukin 2 (IL 2) and IFN gamma. In vitro IL 2 and IFN gamma production in 3 to 6-mo-old, autoimmune MRL-Ipr/Ipr and MRL-+/+ mice was compared with that seen in age- and sex-matched, immunologically normal CBA/J mice. 5 X 10(6) spleen cells were pulsed with 5 micrograms of concanavalin A (Con A), and the cellfree supernatant was assayed for IL 2 and IFN gamma activity at various times up to 72 hr. We found that peak levels of IL 2 in MRL mice were less than 10% of those in the CBA/J. Yet, production of IFN gamma by cells from the autoimmune and normal strains was quite comparable. The addition of murine IL 2 to optimally Con A-stimulated cells from the MRL-Ipr/Ipr or normal mice did not affect the subsequent peak production of IFN gamma. Although the primary producers of IFN gamma in cultures of normal mice bear the Lyt-2+ phenotype, the Lyt-1+2- T-cell subset was found to be the principal source of IFN gamma in the aged MRL-Ipr/Ipr. These data suggest that Lyt-1+ cells from MRL-Ipr/Ipr mice may be differentially responsive to the signal delivered by the same mitogenic lectin with respect to lymphokine production and may indicate a distorted commitment of such cells toward production of IFN gamma and repression of IL 2 synthesis. The relationship between hypoproduction of IL 2, this usual source of IFN gamma, and the autoimmune disease sustained by MRL-Ipr/Ipr mice remains unclear.
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PMID:The cellular basis for immune interferon production in autoimmune MRL-Ipr/Ipr mice. 640 74

Acid-stable interferons (IFN-alpha or IFN-beta) are produced by nucleated cells infected by virus, while acid-labile interferon (IFN-gamma) is synthesized by activated T-lymphocytes. IFN-gamma or an atypical form of acid-labile IFN-alpha have been observed in the circulation of some patients with autoimmune disease. It is believed that autoimmunity and/or viral infections are involved in the pathogenesis of insulin dependent diabetes mellitus. We therefore examined the sera of newly diagnosed diabetic children for the presence of virus-induced or acid-labile IFN. Significant IFN levels (greater than or equal to 8 U/ml) were observed in 11 of 29 patients when compared to 31 healthy children in the same age range. The inhibitor is characterized by species specificity, acid-lability and neutralization with anti-serum for IFN-gamma.
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PMID:Evidence of circulating interferon-gamma in newly diagnosed diabetic children. 644 49

DNA profiles (immunoprints) were generated for 120 patients suffering from early onset pauciarticular chronic arthritis (EOPA-JCA) and > 500 healthy controls utilizing highly polymorphic microsatellites in the vicinity of immunorelevant genes. Six T cell receptor (TCR) markers for the CD3D, TCRDVAJ, TEA, TCRBV6S1, BV6S3, BV6S7 and BV13S2 genes were analysed. Furthermore markers for the cell surface molecule CD40L, for cytokine genes (IL-1A, IL-2, IFN-alpha, FGF-alpha, TNF-alpha), the chromosomal region of the IRF2 and the cytokine receptor gene IL5RA were studied as well as two polymorphisms within the promotor region of the TNF-alpha gene. Coding region polymorphisms were evidenced indirectly by repeat length variation or they were predicted from the microsatellite distribution profiles and then confirmed by direct sequence analysis. Statistical evaluations were performed with respect to known predispositions, predominance of females (> 80%) and HLA-DR and -DQ haplotypes. Cell surface molecules (TCR, CD40L, IL5RA) as well as almost all cytokines (IL-1A, IFN alpha, FGFA, IRF2 region) were excluded as predisposing in our JCA panel. The TNF-alpha microsatellite alleles (GT)10-12 contribute considerably to manifestation of the disease, in HLA-DRB1*11(12) individuals (RR = 12.8). The TNF-alpha allele is not found in linkage disequilibrium with HLA-DRB1*11(12) and may be present on either chromosome 6. Thus, a novel susceptibility factor probably within the TNFA/TNFB gene region has been identified via linkage with the TNF-alpha microsatellite allele. Apparently complex compositions of the genetic background rather than single genes provide the precondition for manifestation of the autoimmune disease EOPA-JCA. Immunoprinting unravels the variability of the immunological genome via the semi-directed microsatellite approach efficiently.
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PMID:Immunoprinting excludes many potential susceptibility genes as predisposing to early onset pauciarticular juvenile chronic arthritis except HLA class II and TNF. 749 83

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease if the central nervous system (CNS). Recently, the type I IFN, IFN-beta-1b was demonstrated to be a useful immunotherapy for MS. During treatment with IFN-beta-1b, toxicity at higher doses has been observed. IFN-tau, discovered for its role in the reproductive cycle, possesses all of the functions normally ascribed to the type I IFNs but lacks the toxicity normally associate with IFN treatment in vitro. We have examined the effects of IFN-tau treatment on experimental allergic encephalomyelitis (EAE), an animal model useful for the study of MS. EAE is a model of Ag-induced autoimmunity that can be modulated by bacterial superantigen to resemble the relapsing-remitting pattern of autoimmune disease observed in MS. IFN-tau was able to prevent development of EAE as effectively as IFN-beta but without associated toxicity such as lymphocyte suppression and weight loss. In addition, IFN-tau was able to prevent superantigen reactivation of EAE akin to the reduction in disease exacerbations observed in IFN-beta-1b treated MS patients. Mechanisms by which IFN-tau may prevent EAE include reduced proliferation in response to the autoantigen myelin basic protein and reduced TNF-alpha production. Thus, IFN-tau may prove to be a promising new IFN therapy for MS in light of its ability to prevent EAE and the lack of toxicity exhibited by this novel IFN.
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PMID:The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity. 754 84

In experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, we have previously shown that the disease is mediated by Th1 cells, which recognize tryptophan 144 as the primary TCR contact point. Here we describe an altered peptide ligand (APL), generated by a single amino acid substitution (tryptophan to glutamine) at position 144 (Q144), which inhibits the development of EAE induced with the native PLP 139-151 peptide (W144). We show that the APL induces T cells that are cross-reactive with the native peptide and that these cells produce Th2 (IL-4 and IL-10) and Th0 (IFN gamma and IL-10) cytokines. Adoptive transfer of T cell lines generated with the APL confer protection from EAE. These data show that changing a single amino acid in an antigenic peptide can significantly influence T cell differentiation and suggest that immune deviation may be one of the mechanisms by which APLs can inhibit an autoimmune disease.
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PMID:An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. 758 31

Disturbances of interferon synthesis with the hyperproduction of unusual kinds of interferons may be the initial step which triggers autoimmune disease through a concatenation of pathological reactions including the disturbance of several immunological and interferon cascades. This fundamental disturbance can result either from a genetic predisposition or from the influence of certain viruses (or viral particles) or both factors together. The administration of interferons to individuals with an underlying or latent autoimmune condition can exacerbate or trigger the disease. AIDS has many features similar to autoimmune disease, including the hyperproduction of aberrant interferon, a type with little or no anti-HIV activity, protectively induced by HIV to allow its continued replication and survival. In other words, while most viruses induce normal IFN which protects the cells against viral infection, HIV induces an abnormal, defective kind of IFN which insures viral survival. The neutralization of hyperproduced interferons by polyclonal or monoclonal antibody produced in mouse, or preferably, human hybridoma, removal via extracorporeal means, or the use of antagonists which diminish the production or biological activity of these interferons can be a therapeutic approach to the management of these chronic diseases. In addition, the extracorporeal removal of different kinds of interferons, autoantibodies, autoantigens and other substances from the organism in certain pathological conditions may be an effective and safe method of treatment for autoimmune diseases and AIDS.
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PMID:A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic. 769 57

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a. 774 99

To examine the complex role of cytokines in the pathogenesis of actively induced murine EAE we measured the levels of a number of cytokines (IL-6, IFN gamma and TNF) in the spinal cord and CSF of mice with active experimental autoimmune encephalomyelitis (EAE) and found them all to be elevated. We next treated mice with antibodies to these three cytokines, which were over expressed in the CNS, to determine if they would alter disease and found the following: anti-IL-6 had no significant effect on disease, anti-IFN gamma exacerbated disease, and anti-TNF either enhanced, had no effect or inhibited EAE depending on the antibody used. We then treated mice with exogenous cytokines, delivered using a recombinant vaccinia virus system, and found that the IL-6 and TNF virus constructs inhibited EAE whereas the IFN gamma construct had no effect on disease. Other cytokine recombinant viruses were also tested and it was found that the IL-1 beta, IL-2 and IL-10 viruses inhibited EAE while an IL-4 virus either had no effect or enhanced disease. We do not know the mechanism of action of the various cytokines in this system, but irrespective of the mechanism(s), this work clearly demonstrates that delivery of select cytokines using recombinant virus-cytokine constructs can provide a powerful means of down-regulating experimental organ-specific autoimmune disease.
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PMID:Cytokines and murine autoimmune encephalomyelitis: inhibition or enhancement of disease with antibodies to select cytokines, or by delivery of exogenous cytokines using a recombinant vaccinia virus system. 782 86

Chronic inflammatory demyelinating polyneuropathy (CIDP) is thought to be an inflammatory autoimmune disease against peripheral myelin. Recently several animal models have suggested that preferential activation of Th1 cell response is central to the pathogenesis of this disease. We studied the function of CD4 positive T cell subsets, Th1 cells and Th2 cells by analyzing their representative secreting cytokines. Th1 cells secrete Interferon gamma (IFH gamma) and Th2 cells secrete Interleukin 4 (IL4). Using enzyme linked immunospot (ELISPOT) assay, a very sensitive single cell analysis system, we enumerated IFN gamma and IL4 secreting peripheral blood lymphocytes in patients with CIDP. Also we examined these cytokines in supernatants of cultured peripheral blood lymphocytes by a very sensitive enzyme linked immunosorbent assay (ELISA), Immunodot assay and westernblot assay. In culture supernatants of CIDP patients' peripheral blood lymphocytes, the levels of both IFN gamma and IL4 were higher during the exacerbation stage than the remission stage. In the remission period, though the levels of IFN gamma and IL4 were low in the supernatants, the ELISPOT assay revealed that the number of IL4 secreting cells was elevated compared with that of IFN gamma secreting cells. Our results suggest that the switch from Th1 to Th2 might play an important role in inducing the remission stage in patients with CIDP.
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PMID:[A study on subpopulation of helper T cells in chronic inflammatory demyelinating polyneuropathy]. 782 23

Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-gamma released after immunologic stimulation such as viral infection. This mechanism may account for the loss of apparent tolerance to self antigens in autoimmune diseases such as insulin-dependent diabetes mellitus.
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PMID:Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma. 786 Jul 30


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