Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen biosynthesis was measured in skin biopsies taken from 13 patients with rheumatoid arthritis before and after at least 6 months' continuous treatment with D-penicillamine, 1.0 g/day. There was a significant 36% reduction in mean collagen biosynthesis (p less than 0.0125) as assayed by 14C-hydroxyproline formation from 14C-proline during 24 h of tissue culture. The changes in 14C-hydroxyproline formation were correlated with the total doses of D-penicillamine taken (r = 0.71, p less than 0.01) and the falls in ESR (r = 0.72, p less than 0.01). No significant change in general protein syntehsis was observed. 500 microgram/mlD-penicillamine added to skil cultures in vitro inhibited both collagen and general protein synthesis (p less than 0.01). It is suggested that the clinical improvement induced by D-penicillamine could reflect an inhibition of collagen proliferation in the synovium.
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PMID:Skin collagen biosynthesis in patients with rheumatoid arthritis treated with D-penicillamine. 45 91

The leucocytes of 22 patients with classic rheumatoid arthritis were investigated with the direct leucocyte migration inhibition technique in agarose as described by Clausen. The leucocytes of 9 patients with degenerative joint diseases and of 9 healthy persons served as controls. Collagen type I and collagen type III were used as antigens. The leucocytes of 22 patients with rheumatoid arthritis showed in 15 cases a migration inhibition with collagen type III and in 10 cases with collagen type I. The inhibition with collagen type III was stronger and more frequent than with collagen type I. The frequent leucocyte migration inhibition with collagen type III in classic rheumatoid arthritis seems to be an expression of possible cell mediated reactivity against that type of collagen which appears especially in rheumatoid synovial tissue.
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PMID:Leucocyte migration inhibition with collagen type I and collagen type III in rheumatoid arthritis and degenerative joint diseases. 63 69

Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non-MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. 128 54

Collagen type II (CII) is a cartilage-specific matrix compound well known as an inducer of an experimental, T cell-dependent autoimmune arthritis, a disease which shows some similarities to human rheumatoid arthritis. Here we report on an HLA-DR7-restricted human CD4 T cell clone (TC9), which was isolated from a healthy donor and recognizes human CII. After screening CNBr fragments of CII and tryptic fragments derived thereof, the T cell epitope could be mapped to amino acid residues 271-285 of the triple helical region of CII that are located within CNBr fragment 11 [alpha 1 (II) CB11]. This epitope was confirmed by a synthetic peptide stimulatory for TC9. The T cell receptor beta chain of TC9 was cloned using the polymerase chain reaction; it comprises V beta 6.7 and contains besides J beta 2.3 and C beta 2 an as yet undescribed sequence for the D segment.
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PMID:Specificity and T cell receptor beta chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual. 137 Apr 17

Collagen-induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F1 is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1a haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II Ba molecule, encoded from the RT1Ba locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the alpha and beta chains of both the RT1a and RT1l haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H-2 Aq). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II, T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.
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PMID:Homologous collagen-induced arthritis in rats and mice are associated with structurally different major histocompatibility complex DQ-like molecules. 153 78

Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA.
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PMID:Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection of the diabetic-resistant subline as a rheumatoid arthritis research tool to characterize the immunopathologic response to human type II collagen. 170 52

Collagen-induced arthritis (CIA) is a chronic polyarthritis induced in mice and rats by immunization with homologous or heterologous type II collagen (CII). In this study, we report on a variety of experiments designed to elucidate the characteristics of CIA and its potential application in the treatment of human disease. The notable results were as follows: Both mouse anti-human-CII monoclonal antibody and a mouse T cell clone reactive to human CII were able to provoke arthritis when i.v. injected into naive mice. When injected together, a synergistic enhancement of the incidence and severity of passive arthritis was seen. However, inoculation with irradiated T cells reactive to human CII could suppress the development of active CIA. Given these results and the fact that CIA closely resembles rheumatoid arthritis both clinically and histologically, we suggest that the CIA animal model provides a good tool for studying the potential of T cell vaccination as a means of treating or preventing human autoimmune diseases.
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PMID:Collagen-induced arthritis--characteristics of the animal model and implications for the treatment of autoimmune disease. 180 81

In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9 +/- 13.8% 1B3.1-positive cells (42.8 +/- 10.4% in patients with rheumatoid arthritis and 28 +/- 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells or in vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.
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PMID:Expression and functions of very late antigen 1 in inflammatory joint diseases. 182 28

Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains.
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PMID:Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies. 183 85

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen-induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.
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PMID:Collagen autoimmunity and arthritis. 305 8


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