IgG3 reactive rheumatoid factor in rheumatoid arthritis: etiologic and pathogenic considerations.
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.
Wong
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A
Department of Internal Medicine, School of Medicine, University of California, Davis 95616, USA.
Kenny
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TP
Ermel
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R
Robbins
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DL
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001483:Base Sequence; D003171:Complement Pathway, Classical; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits; D012217:Rheumatoid Factor / Q000097:blood / Q000276:immunology*; D016415:Sequence Alignment; D013045:Species Specificity; D013583:Synovial Membrane / Q000276:immunology
D000956:Antigens, Viral; D001324:Autoantigens; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007126:Immunoglobulin Allotypes; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D012217:Rheumatoid Factor