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

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)
 ...
PMID:Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. 128 54

Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous matrix protein. We have developed an enzyme-linked immunosorbent assay for the detection of this protein in synovial fluid and serum. The protein has been quantified in these fluids in patients with rheumatoid arthritis (RA), reactive arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control subjects. The protein was detectable in all fluids and the synovial fluid levels were always higher than in serum in paired samples. The highest knee joint synovial fluid levels were found in reactive arthritis patients and the lowest in RA patients with advanced destruction of the knee joint. However, the relative synovial fluid content of COMP was higher in these RA patients than in patients with advanced osteoarthritis. In patients with long-standing reactive synovitis the concentrations decreased. This decrease, however, was less marked than for proteoglycan concentrations. The serum concentrations were low in patients with juvenile chronic arthritis and in patients with RA with advanced cartilage destruction of the studied knee joint. In the other groups serum levels did not differ between groups or from controls.
 ...
PMID:Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. 138 80

Two cartilage specific macromolecules, cartilage oligomeric matrix protein (COMP) and proteoglycan, were quantified by immunoassay in sera of two groups of patients with rheumatoid arthritis (RA) of recent onset to evaluate the prognostic value of such measurements. Patients with rapidly progressive joint destruction had increased COMP concentrations initially, which subsequently decreased. A group with more benign disease, and less extensive joint damage, had normal COMP levels throughout the study period. Serum concentrations of proteoglycan were normal in both groups. Thus measurement of COMP in serum early in the course of RA holds promise as a prognostic marker for development of joint destruction in this disease.
 ...
PMID:Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis. 152 24

Osteocalcin is a non-collagenous bone matrix protein which is released into the circulation and can be measured by radioimmunoassay. Recent studies indicate that serum osteocalcin concentrations are a marker of bone formation. Because bone demineralisation is a common finding in patients with rheumatoid arthritis (RA) the serum osteocalcin concentrations and, in addition, the serum concentrations of 25-hydroxyvitamin D, parathyroid hormone, and calcitonin were measured in 29 patients with RA and in 30 control subjects. Whereas serum osteocalcin concentrations were similar in patients with RA and in control subjects, serum 25-hydroxyvitamin D concentrations were significantly decreased in patients with RA. Serum concentrations of parathyroid hormone and calcitonin in patients with RA and in control subjects were not statistically different. The normal osteocalcin concentrations in patients with RA suggest a normal rate of bone formation in these patients.
 ...
PMID:Serum osteocalcin concentrations in patients with rheumatoid arthritis. 233 13

Proliferative responses of peripheral blood mononuclear cells of rheumatoid or osteoarthritis patients and normal controls stimulated with cartilage components were studied. Two components not studied in previous cellular studies, matrix proteins (fraction A4) and lipoproteins, were used as well as whole extract of cartilage, native and denatured collagen, and proteoglycans. In general, osteoarthritis cells responded less well than the other two groups; this was statistically significant for fraction A4-matrix protein (normal p less than .02, rheumatoid arthritis p less than .025). Fraction A4 sterilized by filtration rather than irradiation gave higher responses in both arthritic groups, but not controls. Antigenic alteration by radiation may explain this difference and, perhaps, the low level of proliferation to all the components seen. The possible role of such cell-mediated responses in chronic arthritis is discussed, and the current and previous reports of cartilage component-induced cellular responses are reviewed.
 ...
PMID:Cellular immune responses to cartilage components in rheumatoid arthritis and osteoarthritis: a review and report of a study. 329 63

Rheumatoid arthritis (RA) sera were compared in a matched, controlled study to non-RA sera for their ability to react in ELISA with antigen preparations extracted from bovine nasal cartilage. Antibodies to matrix proteins, proteoglycans and whole extract were significantly higher in RA sera than in non-RA with the reactivity for matrix proteins giving the largest difference. There was no significant difference between RA and non-RA antibody levels for collagen and collagen alpha chains. By SDS-PAGE, large pore composite gel electrophoresis, and uronic acid analysis, the matrix protein fraction contained 8 major proteins as well as two electrophoretic species of low density proteoglycans distinct from the major high density cartilage proteoglycans. Further fractionation provided a proteoglycan-free preparation containing six major proteins of 66-13 kd with which the RA sera were still highly reactive.
 ...
PMID:Specificity of antibodies in rheumatoid arthritis. I. A controlled study of humoral antibodies to bovine nasal cartilage components. 405 41

Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.
 ...
PMID:Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. 753 84

Familial clustering is a common feature of many different arthritic conditions which can be explained by shared genetic or environmental influences or a combination of these. The aetiology of some of these diseases (e.g. multiple epiphyseal dysplasia, Lesch-Nyan syndrome) is clearly monogenic but the majority of common rheumatic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA) are complex and multi-factorial with a polygenic component. In the last 10 years there has been spectacular progress in unravelling the underlying genetic mechanisms of many monogenic disorders including many that affect the musculoskeletal system. Among these osteogenesis imperfecta (OI) and the Marfan syndrome are striking examples in which molecular defects of matrix protein components of the mesodermal tissues have been revealed. In particular, the power of modern molecular genetics both to test candidate genes (e.g. collagen in OI) and to identify genes where no prior knowledge of the protein defects exists (e.g. fibrillin in the Marfan syndrome) has proved quite remarkable. In the near future many of the techniques that have been applied successfully to these monogenic diseases can be expected to provide insights into the genetic component of common diseases, such as rheumatoid arthritis. However, it is important to realize before embarking on these studies that even monogenic diseases may provide significant problems of analysis and interpretation. Some of these problems are exemplified below (e.g. phenocopies, mosaicism, imprinting).
 ...
PMID:Genes and arthritis. 755 62

Rheumatoid arthritis (RA) is the dominant form of destructive chronic arthritis with the potential to cause substantial disability and permanent functional impairment. The final extent and progression rate with time, however, varies markedly. In order to study effects of intervention and to support early aggressive and atoxic therapy in selected cases, predictive disease markers are needed. Recent advances regarding joint tissue composition and pathophysiology have defined a number of biological marker candidates which need to be explored for possible prognostic information. Some markers are characteristic for RA, such as rheumatoid factors and certain autoantibodies, which although they are more prevalent among patients with aggressive disease are not sensitive as predictors in early disease. Genetic susceptibility markers have been claimed to be good predictors of persisting arthritis in early synovitis clinics, but their role as severity markers in established disease is limited. Unspecific markers of inflammation, notably ESR or CRP when persistently elevated, are useful to monitor disease course and newer markers need to document their superiority over these. Another group of markers are attractive because of enriched or exclusive occurrence in joint tissue, and altered metabolism in joint disease. Thus, collagen type III propeptides, hyaluronates, and neopterin originating in the synovium could be useful, and, in particular, hyaluronate levels indeed do provide some predictive information. Highly tissue-specific cartilage metabolites include aggrecan fragments, collagen II fragments, cartilage oligomeric matrix protein (COMP) and the extraarticular cartilage matrix protein (CMP). When used alone or in combination in early disease some information can be obtained which may in the future facilitate prognostication. Bone metabolism can be monitored and there are different markers for synthesis and resorption. Meanwhile, whilst the new markers are essential research tools, their routine clinical usefulness remains to be proven.
 ...
PMID:Predictors of joint damage in rheumatoid arthritis. 861 19

We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.
 ...
PMID:Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. 890 56


1 2 3 4 5 6 7 8 9 Next >>