Physiology and pathology of rheumatoid factors

Carson, Dennis A.; Pasquali, Jean‐Louis; Tsoukas, Constantine D.; Fong, Sherman; Slovin, Susan F.; Lawrance, Simon K.; Slaughter, Laura; Vaughan, John H.

doi:10.1007/bf01857093

Cited by 46 publications

(18 citation statements)

References 38 publications

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“…A limitation of this study was the absence, from the trial data available to us, of information on rheumatoid factor, which may affect response to treatment (22,23). In addition, only 3 trials had HAQ data available as a measure of physical function, with the remainder of trials providing grip strength data.…”

Section: Discussionmentioning

confidence: 99%

Factors predicting response to treatment in rheumatoid arthritis: The importance of disease duration

Anderson

Wells

Verhoeven

et al. 2000

Arthritis & Rheumatism

436

209

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Section: Discussionmentioning

confidence: 99%

Factors predicting response to treatment in rheumatoid arthritis: The importance of disease duration

Anderson

Wells

Verhoeven

et al. 2000

Arthritis & Rheumatism

436

209

View full text Add to dashboard Cite

show abstract

“…It is well established that there is a direct correlation between the severity of the disease and the titer of these antibodies in patients with RA (19,43). Although the precise pathogenic role of RF in RA has not been defined, a great deal of evidence suggests its participation in sustaining inflammatory synovitis (5,38,43).…”

mentioning

confidence: 99%

Rheumatoid Factors Induce Signaling from B Cells, Leading to Epstein-Barr Virus and B-Cell Activation

Yang¹,

Hakoda

Iwabuchi

et al. 2004

J Virol

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“…Hybridization studies indicate that the human germ line contains only 25-50V1 genes (18,26,34,35). Strong selective pressures must have operated to conserve the basic RF V1 sequence during the evolution and dispersion of the human species (36,37). Possibly, the V1(Rf)-encoded light chain, in combination with an appropriate heavy chain, generates an antibody against an important environmental pathogen.…”

Section: Resultsmentioning

confidence: 99%

Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.

Chen¹,

Albrandt²,

Orida³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the K light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated V -(RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human VK germ-line genes that encode K light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a K V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.Immune responses are controlled by genes that encode histocompatibility antigens, T-cell receptors for antigens, and immunoglobulins. The inherited structural genes for immunoglobulin light and heavy chains dictate the potential antibody repertoire of any individual. However, immunoglobulin genes also undergo extensive rearrangements and somatic mutations during life (1, 2). Both polymorphisms in inherited immunoglobulin genes as well as somatic changes may therefore influence the ability to form autoantibodies. To dissect the importance of the two factors, one must first isolate potential autoantibody structural genes in their germline configuration. This goal has proved difficult to accomplish in outbred human populations.Idiotypes are antigens in the variable (V) portion of immunoglobulins (3,4). In many instances, idiotypic antigens have been localized at or near the antigen binding site. Immunoglobulins that share idiotypic determinants often are related structurally and may represent the protein products of identical or similar antibody V-region genes (5-8).Kunkel and co-workers first demonstrated that several human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated subjects shared idiotypic antigens (9). A majority of these monoclonal RFs also had homologous sequences in the K light-chain V regions (10-13). Subsequent experiments with anti-peptide antibodies localized two of the shared idiotypic determinants, also termed cross-reactive idiotypes, to the second and third complementarity-determining regions of the K light chain. After an analysis of multiple RF light chains with a diverse series of anti-idiotypic reagents, we postulated that the cross-reactive idiotypes were markers for a single...

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Physiology and pathology of rheumatoid factors

Cited by 46 publications

References 38 publications

Factors predicting response to treatment in rheumatoid arthritis: The importance of disease duration

Factors predicting response to treatment in rheumatoid arthritis: The importance of disease duration

Rheumatoid Factors Induce Signaling from B Cells, Leading to Epstein-Barr Virus and B-Cell Activation

Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.

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