Conclusions
Substantial evidence indicates that humoral immunity through antigen-antibody complex formation contributes to the pathogenesis of RA. Several studies have examined the composition of immune complexes present in the synovial fluid of patients with RA. The constituents of these immune complexes have been immunoglobulins and complement components. Only a few polypeptides in these immune complexes have not been identified. These unidentified components account for only a few percent of total proteins present. These results suggest that rheumatoid factors and their antigens are quantitatively the important ingredients of immune complexes in synovial fluid of patients with RA. The immune deposits in the superficial layers of articular cartilage from patients with RA contain RFs and antibodies to type II collagen.
IgG RFs are unique autoantibodies in that they can form immune complexes with pathogenic potential by self-association and without the presence of separate antigen molecules. Self-association becomes possible when the antigenic specificity of IgG RFs is directed to antigenic determinants present on the Fc region of the same molecule. Self-association of IgG RFs is enhanced in a milieu of high concentration of these antibodies and in relative paucity of normal IgG — i. e., conditions that exist in the synovial tissue where IgG RFs are synthesized.
Relatively little attention has been devoted to antigenic specificity of RFs in relation to disease. The self-associating IgG RFs illustrate how the antibody specificity and presence of antigenic determinants can contribute to formation of unique immune complexes. One of the major antigenic determinants for IgM RFs is in the Cγ2-Cγ3 domain interface and involves some of the same amino acids that constitute the site for binding SPA. The specificity for self-associating IgG RFs is directed to the same antigenic determinant. Fc binding proteins from Streptococci and the Fc binding proteins induced by herpes type 1 virus bind to the same or overlapping areas of human IgG. The reasons for this similarity of binding to IgG between microbial Fc binding proteins and RFs is not apparent. This relationship, however, may stimulate the synthesis of some RFs by an internal image autoantiidiotype mechanism.
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Mannik, M., Nardella, F.A. & Sasso, E.H. Rheumatoid factors in immune complexes of patients with rheumatoid arthritis. Springer Semin Immunopathol 10, 215–230 (1988). https://doi.org/10.1007/BF01857226
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DOI: https://doi.org/10.1007/BF01857226