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)

Rheumatoid factor (RF) is a polyclonal autoantibody directed against the Fc portion of IgG. Although the role of RF in patients with rheumatoid arthritis (RA) is unclear, immune complexes that form between RF and IgG can activate the classical complement (C) pathway, leading to pathogenic outcomes involving inflammatory events and tissue damage. The specificity of serum RF and RF produced by rheumatoid synovial cells (RSC) is different. Serum RF has specificity for rabbit IgG and human IgG subclasses IgG1, 2, and 4, but binds poorly to IgG3. The affinity of serum RF for IgG Fc is low, having an association constant of 10(4)-10(5) M-1. RSC RF, however, has specificity for human IgG and high avidity for IgG3. Because of this greater specificity and avidity for IgG3, and because RSC RF may be pathogenically more important than serum RF, an important role for IgG3-reactive RF in RA may exist. Binding of RF to IgG may be dependent on the allotype and glycosylation of IgG. Infectious agents present in RA patients may directly or indirectly induce the production of certain RF. In this communication, we review and expand on several observations examining the role of IgG3-reactive RF in RA including: 1) binding differences between RF derived from RSC and serum; 2) glycosylation characteristics of IgG and its interaction with RF; 3) apparent allotype dependent binding of IgG3-reactive RF; and 4) possible relationship between infectious agents and the production of IgG3-reactive RF. Taken together, these observations suggest an important role for IgG3-reactive RF in better understanding the etiology and pathogenesis of RA.
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PMID:IgG3 reactive rheumatoid factor in rheumatoid arthritis: etiologic and pathogenic considerations. 754 51

In order to evaluate the autoantibody pattern of subjects affected by rheumatoid arthritis (RA) with clinical features of keratoconjunctivitis, we studied 32 out- and in-patients (26 women, 6 men, average age 52 years, average disease duration 5.5 years) at the Division of Rheumatology, Catholic University of Rome. We found keratoconjunctivitis sicca and xerostomia in 22 (68.75%) patients with RA. Rheumatoid factor was present in 17 (53.1%) patients, antinuclear antibodies (ANA) were observed in 15 (48.4%) patients, and anti-rheumatoid arthritis nuclear antigens (RANA) in 22 (68.7%) patients; anti-SSA antibodies were confirmed in 3 (9.4%) patients and anti-SSB antibodies in 2 (6.2%) patients. None of the patients evidenced anti-U1RNP. Although keratoconjunctivitis sicca and xerostomia correlated significantly with the presence of rheumatoid factor, we found no relationship between these two conditions and ANA or anti-RANA antibodies. The high frequency of keratoconjunctivitis sicca and xerostomia in our RA patients is the expression of extra-articular involvement in this disease and is correlated with the presence of rheumatoid factor. ANA and anti-RANA antibodies may represent aspecific polyclonal activation in RA.
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PMID:[Keratoconjunctivitis sicca in rheumatoid arthritis: correlation with the autoantibody pattern]. 761 48

Rheumatoid factor (RF), an autoantibody against the Fc portion of denatured IgG, has long been recognized as an important biologic marker not only for rheumatoid arthritis but also for other auto-immune diseases. In this study, we measured the level of serum RF in four patients with RF positive systemic vasculitis using laser nephelometry. Three patients were diagnosed as polyarteritis nodosa and the other patient was diagnosed as systemic vasculitis without the finding of typical necrotizing vasculitis from biopsies. In the result, we found that the level of RF paralleled the disease activity in these cases. When active phase of the disease, the level of RF showed very high, and after the treatment combined with plasmapheresis, corticosteroid and immunosuppressive agent, the level of RF decreased in accordance with CRP, ESR and clinical features. These suggested that RF was the disease specific marker for RF positive vasculitis and beneficial informations for proper diagnosis and better treatment could be provided by measurement of the level of RF in patients with RF positive systemic vasculitis.
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PMID:[The association of the disease activity of rheumatoid factor positive vasculitis and the level of rheumatoid factor]. 767 Nov 28

Rheumatoid factor (RF) autoantibodies can be produced in healthy individuals after infections or immunizations and thus escape normal tolerization mechanisms. It has not been clear whether such autoantibodies can undergo somatic hypermutation and affinity maturation similar to antibodies to exogenous antigens. We have investigated how these autoantibodies are regulated in normal individuals by analyzing the sequences of monoclonal IgM RFs obtained as hybridomas from donors after immunization. The variable regions undergo extensive hypermutation, but in contrast to antibodies against exogenous antigens, there is a strong selection against mutations that result in replacement of amino acids in the hypervariable, or complementarity-determining, regions. Furthermore, we found no increase in affinity of these RFs with the accumulation of mutations. This suggests that high-affinity variants are tolerized during the hypermutation process and there is a peripheral mechanism operating on certain autoreactive B cells that, while not deleting or anergizing all autoreactive cells, prevents the generation of high-affinity autoantibodies. Comparison of RFs by using the VH1 DP-10 heavy chain variable region segment from both normal individuals and rheumatoid arthritis (RA) patients suggests that RF from RA patients may not be subject to such a controlling mechanism.
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PMID:Control of autoantibody affinity by selection against amino acid replacements in the complementarity-determining regions. 780 46

Rheumatoid factor is of limited value in the diagnosis of rheumatoid arthritis (RA) in West Africa. Consequent upon previous findings, we have studied the role of the absence of antibodies to malaria and human immunodeficiency virus (HIV) as well as the presence of the hepatitis B surface antigen (HBsAg) as diagnostic markers of rheumatoid arthritis in West Africa. We have found a significant association (p < 0.001) between RA and titre of HBsAg, but only between RA and malaria (p < 0.05) when sera with low malaria antibodies were studied. No correlation between either HBsAg or malaria and rheumatoid factor was found and no RA patient was either HIV-1 or HIV-2 positive.
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PMID:The absence of antibodies to malaria and human immunodeficiency virus, and the presence of hepatitis B surface antigen as diagnostic markers of rheumatoid arthritis. 812 6

One of the genetic components of seropositive rheumatoid arthritis has been mapped to a short sequence stretch in the third hypervariable region of the HLA-DRB1 gene. A new concept has emerged, proposing that the shared-sequence motif is functional in determining the clinical patterns of rheumatoid arthritis and the severity of the disease in a codominant mode. Patients with a double dose of the shared sequence tend to have more serious disease manifestations, suggesting a model in which the genetic element is involved in perpetuating the disease. The pathogenetic model in which the shared epitope selectively binds and presents an arthritogenic peptide appears too simplistic to account for these findings. Our understanding of how the shared epitope may contribute to forming the molecular complex of the T-cell receptor, peptide, and HLA-DR molecule is advancing. Molecular analyses of the synovial T-cell infiltrate continue to define the various components involved in recruiting T cells to the site of synovial inflammation. Adhesion molecules, predominantly the endothelial cell ligands vascular adhesion molecule 1 and endothelial leukocyte adhesion molecule 1, attract phenotypically selected T cells with a wide spectrum of specificities. The rheumatoid factor-positive B cells may be important antigen-presenting cells in the joint and may activate T cells with many different specificities. Rheumatoid factor immunoglobulin genes show clear evidence of somatic mutation, indicating a T cell-dependent, antigen-driven process. Thus, multiple factors contribute to the composition of the inflammatory infiltrate and may well modulate the repertoire of T cells recruited to the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interplay of T lymphocytes and HLA-DR molecules in rheumatoid arthritis. 845 67

The past year has witnessed a modest expansion in our understanding of the clinical, diagnostic, and prognostic features of rheumatoid arthritis. Almost every continent has reported prevalence, phenotype, and clinical features of rheumatoid arthritis subpopulations. Reviews of the natural history and therapy of cervical spine disease, Felty's disease, and lung involvement dominate the clinical literature. Rheumatoid arthritis-like syndromes have been reported to occur after immunotherapy with interferon alfa and interleukin-2. There have been case studies on human immunodeficiency virus, cachexia, pregnancy, "pseudosepsis," bone loss, and malignancy in rheumatoid arthritis. Diagnostic criteria and new classifications for functional and global impairment have been published, and new health impairment questionnaires have been evaluated. Novel isotopes and the role of magnetic resonance imaging in damaged joints were discussed. Rheumatoid factor was reaffirmed as a significant prognostic variable, and the roles of immunogenetic loci, sulfur oxidation, and serum matrix proteins were evaluated in early rheumatoid arthritis. Functional status was again verified as a strong prognostic marker.
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PMID:Clinical features, diagnosis, and prognosis in rheumatoid arthritis. 845 69

This retrospective study describes the characteristics of rheumatoid arthritis patients seen at the King Khalid University Hospital, Riyadh over a period of 5 years. One hundred and ninety-five patients with rheumatoid arthritis seen during this period were reviewed. There were 155 females and 40 males (F:M ratio 4:1). Females had a younger age at onset than males (38.6 +/- 13.4 vs 42.9 +/- 13.3 year for male - p = 0.037). The majority of patients (76.4%) described an insidious onset. 45.1% used one or more forms of local medicine. Constitutional symptoms were reported in 78 (40%). Rheumatoid factor was positive in 79.5%. The most frequently involved joints were the proximal interphalangeal (PIP) joints, knees and metacarpophalangeal (MCP) joints. Rheumatoid nodules were observed in 15.9% and keratoconjunctivitis sicca in 14.4%. Most patients used second line drugs. The majority of patients (57.4%) were in functional class 1 and 2. The disease pattern and joint distribution resemble more the pattern reported in developed countries.
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PMID:The expression of rheumatoid arthritis in Saudi Arabia. 860 81

Rheumatoid arthritis and seronegative spondyloarthropathies are rheumatologic diseases that likely are caused by inflammatory reactions occurring in genetically predisposed individuals mounting an immune response to the antigen. Understanding the immunopathology of these diseases provides insight into their etiology, pathogenesis, and a rationale for therapies targeting immune component interactions. Although the antigen in rheumatoid arthritis is not known, several bacterial antigens have been associated with seronegative spondyloarthropathies. These antigens result in an interaction between the human leukocyte antigen-B27 restricted CD8 positive T lymphocytes and the antigen presenting cell, producing an inflammatory response. Rheumatoid factors are autoantibodies directed against the fragment crystallizable portion of the immunoglobulin G. Rheumatoid factor immunoglobulin G immune complexes contribute to the inflammatory events in the rheumatoid joint, and may play an important role in antigen presentation. A novel antigen capture enzyme linked immunosorbent assay was developed that mimicked B cell surface expressed rheumatoid factor. Conversely, a direct binding enzyme linked immunosorbent assay mimicked secreted rheumatoid factor. Comparison of rheumatoid binding enzyme linked immunosorbent assays showed that the physical state of rheumatoid factor can affect binding characteristics. The state of glycosylation of immunoglobulin G may contribute to its antigenic structure. These physical characteristics may be important in rheumatoid factor's pathogenic role in rheumatoid arthritis.
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PMID:Immunologic mechanisms in common rheumatologic diseases. 862 Jun 57

Rheumatoid factor (RF) B cells proliferate during secondary immune responses to immune complexed antigen and antigen specific T cells, but higher affinity RFs are not detected except in patients with rheumatoid arthritis and other autoimmune diseases. Consequently, there must exist highly efficient mechanisms for inactivation of these higher-affinity RF B cell clones under normal circumstances. Exposure of transgenic mice expressing a human IgM RF to soluble human IgG in the absence of T cell help causes antigen specific B cell deletion in 2-3 days. The deletion is independent of the Fas/Fas ligand (FasL) pathway of apoptosis and is preceded by a phase of partial activation involving increase in cell size and expression of B7 and ICAM-1, and transient release of low levels of immunoglobulin. Complete B cell activation involving the formation of germinal centers and sustained high level RF secretion only occurs if T cell help is provided simultaneously. RF B cells exposed to tolerogen remain competent to secrete RF in vitro if provided with an appropriate antigenic stimulus and T cell help. Consequently, death of these cells is not preceded by anergy. Abortive activation/deletion of B cells by antigen in the absence of T cell-derived survival signals may represent the major mechanism for maintaining peripheral tolerance in B cells expressing higher affinity RF. The lack of anergy, and the potential for reactivation before death, provide a means for maintaining RF production under pathologic circumstances, such as may occur in the inflamed rheumatoid synovium.
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PMID:Peripheral deletion of rheumatoid factor B cells after abortive activation by IgG. 901 38


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