PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “AUTOIMMUNE DISEASES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Recent advances in animal models of autoimmune disease].

Various autoimmune diseases can be induced in normal animals by simply manipulating the thymus/T cells. For example, elimination of CD25+CD4+ T cells, which constitute about 10% of peripheral CD4+ T cells of normal mice, leads to the development of various organ-specific autoimmune diseases, such as thyroiditis, gastritis, adrenalitis, insulitis, sialoadenitis, oophoritis, or orchitis. Reconstitution of CD25+CD4+ T cells prevents the autoimmune development. Elimination/reduction of CD25+CD4+ T cells induced by genetical manipulation of T-cell ontogeny or caused by environmental agents, such as virus infection, also causes similar autoimmune diseases in normal mice. These newly developed animal models of autoimmune disease will be useful for elucidating the mechanism of immunologic self-tolerance and pathogenetic mechanism of autoimmune disease.

Animals↗
PubMed1996

A novel anti-microfilament antibody, anti-135 kD, is associated with Raynaud's disease, undifferentiated connective tissue disease and systemic autoimmune diseases.

We report herein the characterization of a human IgG antibody reactive with a nonmuscle 135 kD microfilament-associated protein, anti-135 kD. Using nonmuscle epithelial PtK2 cells as substrate in indirect immunofluorescence, we identified a distinctive pattern of reactivity with microfilaments in sera from 12 of 165 (7.3%) patients investigated for systemic autoimmune diseases and in only 2 of 171 (1.2%) normal and rheumatic disease controls (P < 0.006, 95% Cl 1.46 to 30.1). An association between anti-135 kD and Raynaud's phenomenon (n = 12/14, 85.7%) with or without an associated systemic autoimmune disease was noted. The anti-135 kD specificity was established by several criteria. (1) The fluorescence was periodically distributed along microfilaments and concentrated at focal adhesions for all sera (n = 14). (2) On immunoblots, the 14 sera reacted with a PtK2 polypeptide of 135 kD. (3) IgG purified by blot-affinity from the 135 kD band (alpha-135) reproduced the fluorescent pattern of the original sera while IgG purified from other bands did not. (4) Double immunofluorescence with alpha-135 and anti-alpha-actinin mAb indicated absence of antibody fluorescence at ruffling membranes where a-actinin was distributed. (5) IgG subclass analysis of anti-135 kD revealed that 12 (85.7%) sera are of IgG3 isotype and 2 (14.3%) are of IgG1 isotype while the light chain expression was kappa restricted. This is the first report of an antibody to a 135 kD microfilament protein. Anti-135 kD expand the repertoire of anti-microfilament and anticytoskeletal antibodies in human sera.

Adult↗
PubMed2001

Dendritic cells in autoimmune diseases.

Subclinical autoimmune responses can be frequently detected in healthy individuals. Sustained activation of autoreactive lymphocytes is, however, required for the development of autoimmune diseases associated with ongoing tissue destruction either in single organs or generalized with multiple manifestations. Clinical and experimental evidence suggests that prolonged presentation of self antigens by dendritic cells is crucial for the development of destructive autoimmune disease. We discuss here a simplified threshold model where the key parameters for the magnitude of the autoimmune response are the amount of previously ignored self peptides presented by dendritic cells and the duration of the antigen presentation in secondary lymphoid organs. Multiple factors influence the threshold for the conversion of an autoimmune response to overt autoimmune disease. Frequent or persistent viral infections of the target organ may favor autoimmune disease by increasing the amounts of released self antigens, generating cytokine-mediated bystander activation of self-reactive lymphocytes and/or sustaining a chronic response via neoformation of lymphoid structures in the target organ.

Animals↗
PubMed2000

Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases.

Calreticulin (CRT), a high-affintiy calcium binding protein and chaperone, was recently identified as one of the targets of autoantibodies in coeliac disease. We evaluated the level of IgA and IgG antibodies to CRT in sera from patients with coeliac disease and various autoimmune diseases. The level of antibodies to gliadin (shown previously to cross-react with CTR), isolated enterocytes and tissue transglutaminase were determined for comparison. The mean level of IgA antibodies to CRT was significantly higher (P< 0.001) in sera from coeliac patients with active disease (139.9+/-11.2 AU/+/-SE) than in healthy controls (20.9+/-1.7 AU). In sera of patients with systemic lupus erythematosus (SLE), insulin dependent diabetes mellitus (IDDM), multiple sclerosis (MS) and autoimmune thyroiditis (AT) or inflammatory bowel disease (IBD) the mean level (25.8+/-3.7 to 38.1+/-5.6 AU) did not exceed the cut-off value. A low level of these antibodies, however, was detected in some sera of patients with MS and IBD. The level of IgG anti-CRT antibodies was increased in coeliac patients (mean 125.4+/-8.0 AU, P< 0.001) when compared to that in healthy controls (33.9+/-2.3 AU). The IgG anti-CRT antibodies were also detected in about 30% of SLE patients sera (54.1+/-3.6 AU, P< 0.001), but the mean level reached only half that detected in coeliac patients.

Adolescent↗
PubMed2003

A new clinicopathological entity of IgG4-related autoimmune disease.

BACKGROUND: Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. METHODS: To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. RESULTS: In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. CONCLUSIONS: These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved. Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.

Aged↗
PubMed2004

Profiles of gene expression in human autoimmune disease.

Human autoimmune diseases arise from complex interactions between genetic and environmental factors, result from immune attack upon target tissues, and affect 3-5% of the population. We compared gene expression profiles (>4000 genes) in the peripheral blood mononuclear cells of normal individuals after immunization to individuals with four different autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and multiple sclerosis). All autoimmune individuals, including unaffected first-degree relatives, share a common gene expression profile that is completely distinct from the immune profile. Therefore, this expression pattern is not simply a recapitulation of the immune response to nonself, is not a result of the disease process, and results, as least in part, from genetic factors. Surprisingly, these genes are clustered in chromosomal domains suggesting there is some genome-wide logic to this unique expression pattern. These data argue that that there is a constant pattern of gene expression in autoimmunity that is independent of the specific autoimmune disease and clinical parameters associated with any individual autoimmune disease.

Autoimmune Diseases↗
PubMedDate not supplied

Oncogenes, growth factors, and autoimmune diseases (review).

Autoimmune diseases are benign proliferative diseases characterized by the expansion and activation of the autoreactive immune cells and the proliferation of connective tissue elements. Because both cytokines and oncogenes products are necessary for expansion of immune cells, it is possible that inappropriate activation of oncogenes might influence cytokine and lymphokine secretion as well as the expression of immune response genes necessary for the development of autoimmunity in a susceptible individual. At least four gene families of the immune system are involved in the induction and perpetuation of autoimmunity: 1) genes associated with the major histocompatibility complex, 2) germline immunoglobulin genes, 3) T cell receptor genes, and 4) complement genes. The hypothetical genetic locus responsible for the induction of autoimmunity is the "rheumogene". Oncogenes are obvious candidates for rheumogenes and activation of such genes may be necessary for the development of autoimmunity. Certain protooncogenes are activated in systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, progressive systemic sclerosis, and dermatomyositis, supporting this hypothesis. However, the activation of oncogenes in autoimmunity is not associated with gene translocation, deletions, point mutations, loss of regulatory sequences, or amplification, indicating that autoimmunity involves different mechanisms of oncogene activation than do many malignancies. Oncogene expression in autoimmune diseases tends to mimic the expression of oncogenes in normal activated lymphocytes, macrophages, and fibroblasts. Rheumogenes, if they exist, may be disordered regulatory genes which suppress or enhance the expression of cellular oncogenes in a non-malignant fashion. The existence of regulator gene demethylation and the presence of DNA-binding proteins specific for oncogene regulator sequences provide support for the concept of that regulator gene dysfunction, rather than oncogene activation per se is the more primary event in autoimmune diseases.

Animals↗
PubMed2003

[Cardiac involvement in systemic autoimmune disease].

Systemic autoimmune diseases form a diverse group which includes: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, dermato-polymyositis, Wegener's granulomatosis, Sjögren syndrome. Although multisystem involvement is the hallmark of these diseases, the heart seems to be less affected than other organ systems. The aim of the study was to study possible cardiac abnormalities in patients with documented systemic autoimmune diseases and to assess whether there was any relation between antiphospholipid, anti-dsDNA antibodies and myocardial dysfunction findings. 76 patients (53 with SLE, 9 with MCTD, 8 with scleroderma, 6 with Wegener's granulomatosis) were subjected to our study, 69% of these patients manifested cardiac involvement, based on two-dimentional echocardiografic examination (36%--post-inflammatory valvular thickening, 20%--pericardial effusions, 15%--valvular regurgitation, 7%--left atrial enlargement, 5%--left ventricular hypertrophy, 4%--left ventricular dysfunction). None of the patients showed characteristic, acute Libman-Sacks endocarditis, which probably can be explained by chronic corticosteroid-treatment. Clinical evidence of cardiac abnormalities has been observed, in as many as 58% of cases with positive echocardiographic findings. The frequency and extend of cardiac pathology positively correlated with the detection of antiphospholipid antibodies. No such relationship was observed in patients with the presence of very high titers of antinuclear antibodies (anti-dsDNA). In conclusion, our results indicate that echocardiography is a useful method for assessment and monitoring cardiac involvement in the systemic autoimmune diseases.

Adolescent↗
PubMed1982

Membrane-binding antibodies in patients with Graves' disease and other autoimmune diseases.

Abnormally high levels of activity (BA) of immunoglobulins (Igs) to membranes containing TSH receptors were observed in patients with Graves' disease. The assay to detect such BA used guinea pig fat as the membrane source. [125I]Protein A was used to develop the binding antibodies (in serum or IgG). The assay was able to detect specific BA in microgram quantities or less of IgG in about 50% of the sera of patients with Graves' disease. The presence or amount of serum BA did not correlate consistently with either the presence in serum of TSH binding inhibitory Ig or the clinical estimate of thyrotoxicity in Graves' disease. High levels of BA were frequently found in sera of patients with other autoimmune diseases, such as Hashimoto's thyroiditis, rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus. However, BA found in the latter disorders frequently was positive not only when using fat cell membranes but also when using liver kidney, or skeletal muscle membranes. The assay may detect a heterogeneous population of Igs binding specifically to membranes and may reflect a general state of autoimmunity.

Adipose Tissue↗
PubMed1992

Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases.

BACKGROUND: Cyclosporine is an immunosuppressive drug that is used to treat patients with autoimmune disease as well as patients who have received allografts. The drug can cause renal damage, but the incidence of and risk factors for nephropathy in patients treated with cyclosporine for autoimmune or inflammatory diseases are not known. METHODS: We analyzed data from renal biopsies performed in 192 patients (129 adults and 63 children) who had been treated with cyclosporine for insulin-dependent diabetes mellitus of recent onset, uveitis, psoriasis, Sjögren's syndrome, or polychondritis. The mean (+/- SD) initial dose of cyclosporine was 8.2 +/- 2.8 mg per kilogram of body weight per day, and the duration of treatment was 4 to 39 months (median, 13). RESULTS: Forty-one patients (37 adults and 4 children) had cyclosporine-induced nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations, or both. As compared with patients in whom nephropathy did not develop, these patients received a larger initial dose of cyclosporine (9.3 +/- 2.8 vs. 8.0 +/- 2.8 mg per kilogram per day), had a larger maximal increase in the serum creatinine concentration above base-line values (101 +/- 77 percent vs. 50 +/- 33 percent), and were older (31 +/- 13 vs. 23 +/- 12 years). These three variables were shown by multivariate logistic-regression analysis to be significant risk factors. The duration of the elevation in the serum creatinine concentration and the occurrence of elevated blood pressure were not additional risk factors. CONCLUSIONS: Nephropathy is an important potential effect of cyclosporine therapy. The risk of its development in patients with autoimmune diseases who are treated with cyclosporine can be minimized by allowing a dose no higher than 5 mg per kilogram per day and avoiding increases in serum creatinine of more than 30 percent above the patient's base-line value.

Adolescent↗
PubMed2005

Accelerated atherosclerosis in patients with systemic autoimmune diseases.

Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis, the major underlying cause of CVD. In patients with systemic autoimmune diseases, it has been shown that traditional risk factors for CVD cannot completely explain the prevalence of atherosclerosis. Therefore, in addition to these traditional factors, nontraditional risk factors are suggested to contribute to atherogenesis. All risk factors, traditional and nontraditional, contribute to endothelial activation that, followed by endothelial dysfunction, is seen as one of the first steps in this process. This review updates information on the factors that contribute to accelerated atherosclerosis in patients with systemic autoimmune diseases, such as disease-related factors, inflammatory mediators, and advanced glycation end products.

Atherosclerosis↗
PubMed1999

CD44 variant isoforms on blood leukocytes in chronic inflammatory bowel disease and other systemic autoimmune diseases.

We have described recently that TNBS-induced colitis, an animal model of chronic inflammatory bowel disease (IBD), can be cured by treatment with anti-CD44v7. This finding led us to evaluate whether CD44v7 may be of functional importance in patients with IBD. Expression of CD44 variant isoforms (CD44v) has been evaluated on PBMC of 46 patients with IBD, 43 patients with autoimmune diseases not affecting the gastrointestinal tract, 26 patients with nonautoimmune disease, and 24 healthy donors. In all groups, expression of CD44v on freshly harvested PBMC was not above or was borderline above background levels. After in vitro stimulation, expression of CD44 standard (CD44s) and CD44v6 was strongly up-regulated. Exclusively on PBMC of patients with autoimmune disease, high expression of CD44v3 and CD44v7 was observed. CD44v3 and CD44v7 were mainly expressed on subsets of CD4+ lymphocytes, B cells, and monocytes; CD44v6 was predominantly detected on CD4+ and CD8+ cells. Considering functional activity, CD44v7 apparently exerted a dual effect. After culturing PBMC in the presence of anti-CD44v7, a higher percentage of cells produced IL-10. This was irrespective of whether the PBMC were derived from healthy donors or from patients with autoimmune disease or IBD. On the other hand, PBMC of all donors proliferated upon cross-linking of CD3 and CD44s or CD3 and CD44v6. Instead, costimulatory activity of CD44v7 was seen only in PBMC of patients with autoimmune disease and IBD. Because expression and function of CD44v7 in patients with systemic autoimmune disease and IBD have been much like the ones in mice suffering of TNBS-induced colitis, it is tempting to speculate that blockade of CD44v7 could also be of therapeutic relevance in the human diseases.

Adult↗