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)

A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.
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PMID:In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice. 248 Mar 83

B6-lpr/lpr mice develop massive T cell lymphoproliferation, as associated with autoimmune disease. We found a reduced NK activity in the spleen of B6-lpr/lpr mice. Neonatal thymectomy markedly retarded the development of lymphoproliferation and the development of autoantibodies in the B6-lpr/lpr mice. These animals had a higher level of NK activity in the spleen. When the neonatally thymectomized B6-lpr/lpr mice were given anti-asialo GM1 serum (30 microliter) four times at 6-day intervals, initiated at the 8th-10th postnatal week, these mice developed lymphoproliferative disorders and splenomegaly, concomitantly with depression of NK activity. It is therefore tempting to speculate that NK cells are involved in the regulation of the occurrence of lymphoproliferative disorders.
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PMID:Does depression of NK activity cause lymphadenopathy in lpr mice? 326 41

Selective immunoglobulin A (IgA) deficiency (sIgAD) is associated with certain autoimmune states. Increased production of autoantibodies and eventual development of overt autoimmune disease are related in part to genetic and environmental factors as well as to the immune deficiency. We surveyed serum specimens from 60 healthy subjects with sIgAD for the presence of 21 different autoantibodies by enzyme-linked immunosorbent assays. The frequencies of 16 autoantibodies were higher in sIgAD patients than in normal healthy controls. Autoantibodies to Jo-1 (28%), cardiolipin (21%), phosphatidylserine (20%), Sm (15%), asialo-GM1 (21%), sulfatide (32%), sulfoglucuronyl paragloboside (11%), and collagen type I (10%) were detected at high frequencies in comparison to those of normal healthy controls. Many of the serum samples were multireactive (i.e., exhibited binding to more than two autoantigens). Forty percent (24 of 60) of sIgAD serum samples reacted against six or more autoantigens; 10% (6 of 60) of sIgAD serum samples were not reactive with any of the 21 autoantigens. Three percent (7 of 209) of consecutive serum samples submitted for autoimmune antibody analysis that were positive for autoantibodies were from patients with IgA deficiency. Our finding of an increased frequency of autoantibodies in sIgAD patients supports the notion of polyclonal stimulation by repeated environmental stimuli as an etiologic mechanism. Alternatively, the increased frequency may be caused by a dysregulation of the immune response in such individuals. The mere detection of autoantibodies cannot predict whether a subject with sIgAD will develop an autoimmune disease or determine which specific disease will emerge.
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PMID:Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. 758 26

Oligoclonal B-lymphoblastoid cell lines (LCL) were blindly established by nonimmunized protocol from natural populations of two normal persons and 8 autoimmune disease patients using Epstein-Barr virus (EBV)-induced transformation. We systematically screened these LCLs on antibodies against a panel of glycolipids using liposome immune lysis assay (LILA). Eventually we found antibodies to 12 out of 15 compounds containing CTH, globoside, Forssman, paragloboside, CPH, sulfatide, NAGM3, NGGM3, i active glycolipid, GM1, GA1 and GA2 in 81 out of 950 LCLs from normal PBL, and antibodies to 2 out of 15 compounds containing sulfatide and CPH were also detected in 11 out of 430 LCLs from autoimmune disease patients. Unexpectedly, the antibody repertoire of LCLs from autoimmune disease patients was impoverished. The possibility of the EBV technique for production of various kinds of human monoclonal antibodies (MAbs) to glycolipid was shown.
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PMID:Anti-glycolipid antibodies produced by Epstein-Barr virus (EBV)-transformed oligoclonal B cell lines obtained from normal persons and autoimmune disease patients. 775 82

Immune-mediated motor neuropathies are most often disorders manifest clinically by slowly progressive, asymmetrical, distal weakness, starting in the hands more often than the legs. In some cases, electrophysiological findings show multifocal conduction block along the length of motor axons. Other patients have findings consistent with only axonal loss. Laboratory testing is unremarkable except for high-titre serum autoantibodies to GM1 and other neural antigens. Diagnosis of immune-mediated motor neuropathies provides an opportunity for effective immunomodulating therapy that can significantly improve quality of life in affected patients. The identification of antigenic targets of serum autoantibodies in patients with motor neuropathies lends hope that immunotherapies to specifically treat the autoimmune disorder can be developed.
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PMID:Chronic motor neuropathies and lower motor neurone syndromes. 859 19

Insulin dependent (type 1) diabetes mellitus appears to be a genetically determined autoimmune disease. Gangliosides have been implicated in type 1 diabetes as antigenic determinants recognized by islet cell antibodies (ICA) and shown to be able to modulate autoimmune phenomena in experimental diabetes. In order to explore in type 1 diabetes the humoral immune reactivity against gangliosides, taking into account their pancreatic localization and molecular characteristics, antibodies to gangliosides GM3, GM2, GM1, GD3, GD1a, GD1b, and GT1b have been investigated in sera from new onset type 1 diabetics and relatives of type 1 diabetic patients with or without insulin (CIAA) and/or islet cell autoantibodies. Using a purposefully designed sensitive ELISA method we found that presence of antibodies directed against the pacreatic disialo-ganglioside GD3 in a significant percentage of newly diagnosed type 1 diabetics (p < 0.001 vs normal controls) but not in CIAA and/or ICA positive relatives of type 1 diabetics. These findings confirm the involvement of gangliosides in autoimmune phenomena related to type 1 diabetes and suggest disialo-ganglioside GD3 as target of a humoral immune response associated with the onset of insulin-dependent diabetes.
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PMID:Anti-ganglioside antibodies in new onset type 1 diabetic patients and high risk subjects. 888 21

In order to investigate the hypothesis that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease related to the acute inflammatory form of Guillain-Barre Syndrome (GBS), we studied 40 patients, 40 age and sex matched controls with other forms of peripheral neuropathy (ONP) and 37 controls from the same family or household (FC). We sought antibodies to gangliosides GM1 and LM1 by enzyme linked immunoassay (ELISA) confirmed by immuno-overlay. Only 6 (15%) CIDP patients had IgM antibodies to ganglioside GM1 (GM1) and none had IgG antibodies. We found IgM antibodies to ganglioside LM1 in 2 (5%) and IgG antibodies in 4 (10%) CIDP patients. Antibodies of IgG or IgM class were detected by ELISA to chondroitin sulphate C or sulfatide in up to 7.5% of CIDP patients. There were IgM antibodies in 3 (7.5%) and IgG in 4 (10%) patients against 25, 28 or 36 kD myelin proteins identified by immunoblot. Antibodies to any of these candidate myelin autoantigens were not significantly more frequent in CIDP than FC or ONP controls. Sera from 5 CIDP patients with active disease which subsequently responded to plasma exchange did not induce more demyelination upon intraneural injection into rat sciatic nerve than ONP sera. Serum tumor necrosis factor alpha (TNFalpha) concentrations were not increased in any of the CIDP patients. Serological evidence of Campylobacter jejuni (Cj) infection was present in 4 (10%) CIDP patients. IgM antibodies to cytomegalovirus (CMV) were not detected in any sera. CIDP is not commonly associated with either of these infections or with an antibody-mediated response to any of these glycolipid or myelin autoantigens.
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PMID:Immunological investigation of chronic inflammatory demyelinating polyradiculoneuropathy. 905 68

We demonstrate that the receptor binding moiety of Escherichia coli heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA/1 mice at the base of the tail with type II collagen in the presence of complete Freund's adjuvant normally leads to arthritis, as evidenced by inflammatory infiltration and swelling of the joints. A separate injection of EtxB at the same time as collagen challenge prevented leukocyte infiltration, synovial hyperplasia, and degeneration of the articular cartilage and reduced clinical symptoms of disease by 82%. The principle biological property of EtxB is its ability to bind to the ubiquitous cell surface receptor GM1 ganglioside, and to other galactose-containing glycolipids and galactoproteins. The importance of receptor interaction in mediating protection from arthritis was demonstrated by the failure of a non-receptor-binding mutant of EtxB to elicit any protective effect. Analysis of T cell responses to collagen, in cultures of draining lymph node cells, revealed that protection was associated with a marked increase in interleukin 4 production concomitant with a reduction in interferon gamma levels. Furthermore, in protected mice there was a significant reduction in anti-collagen antibody levels as well as an increase in the IgG1/IgG2a ratio. These observations show that protection is associated with a shift in the Th1/Th2 balance as well as a general reduction in the extent of the anti-type II collagen immune response. This suggests that EtxB-receptor-mediated modulation of lymphocyte responses provides a means of preventing autoimmune disease.
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PMID:Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of Escherichia coli heat-labile enterotoxin. 914 30

Multifocal motor neuropathy is a peripheral nervous system disease described among chronic inflammatory demyelinating polyneuropathies. It is characterized according to both clinical criteria, including chronic asymmetric and multifocal deficit which starts and remains prominent in the upper limbs, and electrophysiological criteria, including persistent multifocal motor conduction blocks in motor nerves. High titers of serum antiganglioside GM1 antibodies are discovered in nearly 40% of cases. Steroids and plasma exchange are not efficient. High doses of intravenous immunoglobulins (i.v.Ig) improved symptoms in the majority of open and controlled published studies. The quality of the response to i.v.Ig may worsen in some patients after a variable number of infusions, leading to immunosuppressive treatments mainly with oral or intravenous cyclophosphamide. Its etiology is unknown but the frequent presence of anti-GM1 antibody high serum titers, the pathological findings in some rare morphological studies, and the response to i.v.Ig favor the hypothesis of an autoimmune disorder.
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PMID:[Multifocal motor neuropathy: an individualized disease of the peripheral nervous system]. 936 36

Oral administration of disease-specific autoantigens can prevent or delay the onset of autoimmune disease symptoms. We have generated transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, at levels up to 0.05% of total soluble protein. To direct delivery of plant-synthesized insulin to the gut-associated lymphoid tissues, insulin was linked to the C-terminus of the cholera toxin B subunit (CTB). Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin. Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes. Feeding transgenic potato tissues producing insulin or CTB protein alone did not provide a significant reduction in insulitis or diabetic symptoms. The experimental results indicate that food plants are feasible production and delivery systems for immunotolerization against this T cell-mediated autoimmune disease.
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PMID:A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes. 978 49


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