Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major histocompatibility complex on the sixth chromosome controls expression of a complex series of cell surface antigens which comprise the human leukocyte antigen (HLA) system. These markers, beyond their importance in human organ transplantation, have been demonstrated to occur with an increased prevalence in certain disease states. The group of conditions showing the closest association with specific HLA antigens are the "spondyloarthropathies." These include ankylosing spondylitis (AS), Reiter's syndrome (RS), psoriatic arthritis (PsA), and the arthritis of inflammatory bowel disease (AIBD). Clinical and radiographic studies were made of 310 unrelated caucasoid patients with seronegative arthritis. HLA-A, B, C, and DR typing were performed using the microdroplet lymphocyte cytotoxicity test. Statistically increased prevalences of A26, B27, and Bw38 were observed, while B27 was associated with spinal involvement regardless of diagnosis (90 percent in AS p less than 0.0001). Experiments found A26 (23 percent p less than 0.001) and Bw38 (38 percent p less than 0.0001) in patients with PsA. Spondyloarthritis patients with spinal involvement who lacked B27 frequently had B7. The HLA DR typing for seven specificities was carried out in 196 patients. It was found that DRw4 (52 percent p less than 0.03) and DRw7 (39 percent p less than 0.04) were increased in the PsA patients. This study further confirms the close association of HLA antigens and the spondylarthropathies.
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PMID:The major histocompatibility complex. 695 Jun 86

A search for anti-Ro or anti-nRNP antibodies by precipitin analysis among a population of 64 patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease was undertaken. The 25% of SLE patients with anti-Ro did not have any distinct clinical features, compared to patients without anti-Ro or to anti-nRNP patients with SLE or mixed connective tissue disease. However, these patients did have a significantly greater frequency of rheumatoid factor (80%). Most importantly however, patients with anti-Ro had a significantly increased frequency of HLA-B8 (81%) and HLA-DRw3 (100%) compared to patients with anti-nRNP (B8--29%; DRw3--33%) or SLE patients without such antibodies (B8--41%; DRw3--25%). These data suggest the existence of a specific immune response gene for Ro close to the D region of the major histocompatibility complex.
Arthritis Rheum 1980 Nov
PMID:Serologic subsets in systemic lupus erythematosus: an examination of autoantibodies in relationship to clinical features of disease and HLA antigens. 696 93

Seven inbred rat strains were tested for susceptibility to experimental type II collagen-induced arthritis and for development of cellular immunity to type II collagen by delayed hypersensitivity skin testing. WF (RT1u), LEW (RT1l), and DA (RT1a) were the most susceptible of the strains tested with respect to incidence (greater than 95%) and severity of disease. LEW and DA were strongly skin test reactive to calf type II collagen. BUF (RT1b) developed moderate skin test responses to calf type II collagen and showed low susceptibility to collagen arthritis (1/8). MAXX (RT1n), LEW.B3 (RT1nvl), and AUG (RT1c) were not susceptible to collagen arthritis and showed negative to very weak skin test responses to type II collagen. Disease susceptibility was inherited as a dominant trait in the F1 progeny of (WF X LEW.B3) matings. These data suggest that clinical expression of experimental collagen-induced arthritis and immune responsiveness to type II collagen are controlled in part by genes within or closely linked to the rat major histocompatibility complex--RT1.
Arthritis Rheum 1981 Jun
PMID:Immunogenetic control of experimental type II collagen-induced arthritis. I. Susceptibility and resistance among inbred strains of rats. 697 65

Denaturated beef collagen was tested for its ability to induce the production of leukocyte inhibition factor among the peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal individuals. Responsiveness, defined as the production of leukocyte inhibition factor sufficient to cause greater than 20% inhibition of leukocyte migration, was significantly (P less than 0.001, X2 = 31.1) associated with HLA-DR4. All HLA-DR4 positive individuals, including subjects without any evidence of synovitis, were collagen responders. There was no significant (P = 0.3) difference in the absolute reactivity of HLA-DR4+ versus HLA-DR4- individuals to respond to another antigen, Candida albicans. Collagen reactivity required interactions between macrophages and T cells and was directed against determinants inherent in the linear polypeptide, (Gly-Pro)n. In 5 normal HLA-DR4- nonresponders tested, absence of discernable reactivity to collagen was associated with the presence of antigen-specific, radiosensitive suppressive T cells. These studies suggest that during the physiologic metabolism of collagen all individuals are exposed to Gly-Pro determinants normally buried in the interstices of the collagen triple helix. In individuals whose major histocompatibility complex contains genes linked to those coding for HLA-DR4, this results in the activation of reactive T cells. Conversely, in individuals lacking these genes, collagen-specific suppressive cells predominate.
Arthritis Rheum 1981 Aug
PMID:Regulation of immune reactivity to collagen in human beings. 702 41

Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.
Semin Arthritis Rheum 1994 Jun
PMID:Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic implications. 752 51

Susceptibility to collagen-induced arthritis (CIA), a murine model of autoimmune arthritis, is strongly linked to only two major histocompatibility complex (MHC) haplotypes, H-2q and H-2r. In order to identify the determinants of type II collagen (CII) required to induce arthritis in H-2r-bearing mice, B10.RIII mice were immunized with bovine, chick or human CII. Only bovine CII induced significant arthritis and autoantibodies. When the major CNBr peptides of bovine collagen were isolated and used for immunization, only mice immunized with CB8, representing CII 403-551, developed arthritis. To identify immunogenic epitope(s) within CB8, a panel of synthetic peptides representing overlapping sequences of the bovine peptide was generated. When each peptide was cultured with T cells from B10.RIII mice immunized with CII, one peptide, representing CII 430-466, contained a major T-cell epitope. By using an in vitro lymphokine production assay, the T-cell epitope was further narrowed to CII 442-456. These findings suggest that a T-cell determinant important for the initiation of arthritis in B10.RIII (H-2r) mice is located within a 15 amino acid sequence, residues 442-456 of bovine CII.
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PMID:Collagen-induced arthritis in B10.RIII mice (H-2r): identification of an arthritogenic T-cell determinant. 754 May 90

To investigate the regulatory effects of the prototypic Th2 lymphocyte products and potential immunotherapeutic agents interleukin-4 (IL-4) and IL-10 on macrophages differentiated in vitro under different cytokine-defined environments, blood monocytes were incubated for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor or IL-4. The effect of monocyte culture in the presence or absence of serum was also investigated. Functional responses by 7-day-cultured cells to IL-4, quantified as decreased CD14 expression and suppression of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta production, and as a positive response, increased CD23 expression, were compared directly with the responses by monocytes from which they were derived. In response to IL-10, decreases in LPS-induced TNF-alpha and IL-1 beta production and reduction in the expression of major histocompatibility complex (MHC) class II antigens were examined. Seven-day cultured monocytes/macrophages showed (1) diminished TNF-alpha production in response to IL-10 but not IL-4 (2), diminished IL-1 beta production in response to both IL-4 and IL-10, and compared with fresh monocytes (3), diminished CD14 expression in response to IL-4, and (4) a lesser increase in CD23 expression in response to IL-4. This was the case regardless of the cytokine in the presence of which the cells had been cultured for 7 days. Monocytes cultured for 7 days in GM-CSF expressed increased levels of MHC class II and LPS-induced TNF-alpha and responded inefficiently to IL-10 for decreased MHC class II. The responses by monocytes cultured for 7 days with GM-CSF resemble the published properties of synovial fluid macrophages from patients with chronic inflammatory arthritis. The study highlights the complexity of monocyte/macrophage responses to the immunoregulatory cytokines IL-4 and IL-10 and concludes that responses to IL-4 and IL-10 by blood monocytes may not be representative of responses by their differentiated or activated counterparts.
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PMID:Monocytes cultured in cytokine-defined environments differ from freshly isolated monocytes in their responses to IL-4 and IL-10. 754 Jun 42

Antigen-specific T cell activation requires two independent signalling events, one mediated through T cell receptor engagement by the antigen-presenting cell-expressed peptide/class II major histocompatibility complex, and the second through the cognate interactions of costimulatory molecules expressed on the T cell and antigen-presenting cell. There is evidence from in vitro and in vivo experimental systems suggesting that the CD28/B7 costimulatory pathway is crucial for induction of maximal T cell proliferation and T helper-B cell collaboration for IgG production. This pathway can be blocked by CTLA-4-Ig, a soluble form of CTLA-4 which binds with high avidity to the CD28 ligands, B7-1 and B7-2. Here, we show that CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC). Anti-BIIC antibody titers are reduced in CTLA-4-Ig-treated rats compared to diseased control animals. Histologically, joints from CTLA-4-Ig-treated animals show no histological abnormalities, in contrast to control antibody-treated animals, which show complete erosion of the articular cartilage and bone. Despite the efficacy of CTLA-4-Ig in preventing clinical and histological signs of arthritis and reducing antibody responses to BIIC, delayed type hypersensitivity responses to collagen 18 d or more after CTLA-4-Ig treatment ends are similar in CTLA-4-Ig-treated and untreated rats, suggesting that the prolonged disease suppression observed does not result from induction of T cell anergy.
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PMID:Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig. 754 97

Extensive studies in different ethnic groups have associated the susceptibility to development of rheumatoid arthritis (RA) with the third hypervariable region of the major histocompatibility complex (MHC) HLA-DR beta 1 molecule. On the basis of recent findings in the experimental mouse model of collagen-induced arthritis, Eric Zanelli, Miguel Gonzalez-Gay and Chella David propose that the HLA-DRB1 locus is associated with protection to RA and that the actual arthritogenic peptide-presenting molecule is HLA-DQ. Thus, the development of RA would depend upon the expression of the susceptible DQ allele and the nonprotective DRB1 alleles, along with environmental factors that trigger the autoimmune process.
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PMID:Could HLA-DRB1 be the protective locus in rheumatoid arthritis? 754 77

The evolution of Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi outer surface proteins (Osps) A or B was assessed to investigate the role of immunity to OspA or B in infection and pathogenesis of Lyme disease. Antibodies to OspA or B protect immunocompetent C3H/HeJ or C.B.17 severe combined immunodeficient (scid) mice from challenge with B. burgdorferi. Moreover, arthritis in infected C3H mice resolves with the rise of high titers of B. burgdorferi specific antibodies, including OspA and B, whereas disease persists in scid mice--suggesting that the regression of arthritis may be due to the development of borreliacidal OspA or B antibodies. To evaluate the course of Lyme borreliosis in OspA or B tolerant mice we developed transgenic mice that expressed OspA or B under control of the major histocompatibility complex (MHC) class I promoter. Mice carrying OspA or B transgenes on a C3H/HeJ (C3H, disease-susceptible) or C57BL/6 (B6, disease-resistant) background, immunized with OspA or B, did not mount a humoral or cellular immune response to OspA or B, respectively, but responded normally to other B. burgdorferi antigens. The evolution of Lyme borreliosis, including infection and the development of arthritis and carditis, was similar in transgenic and nontransgenic littermates suggesting that an OspA or B immune response is not singularly involved in either the genesis or regression of Lyme disease in C3H or B6 mice.
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PMID:Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B. 756 61


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