Assessment of the potential pathogenicity of type ii collagen autoantibodies in patients with rheumatoid arthritis. Evidence of restricted IgG3 subclass expression and activation of complement C5 to C5a
✍ Scribed by W. C. Watson; M. A. Cremer; P. H. Wooley; A. S. Townes
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 616 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
IgG subclass analysis by enzyme-linked immunosorbent assay of the autoantibody to native type I1 collagen, detected in 9 patients with classic or definite rheumatoid arthritis, demonstrated a predominance of IgG3 autoantibody. Gm allotyping revealed no obvious association with a particular phenotype. In comparative studies, IgG antibodies to the capsular polysaccharides of pneumococci and tetanus toxoid protein in these same patients consisted predominantly of IgG2 and IgG4. Purified type I1 collagen autoantibody from 3 of these patients activated complement C5 to C5a when bound to human cartilage in vitro, as measured by radioimmunoassay. These results represent direct evidence of a potential pathogenic role for this autoantibody in rheumatoid arthritis.
The pathogenesis of rheumatoid arthritis (RA) involves immune mechanisms directed against either exagenous antigens and/or endogenous connective tis-sue autoantigens (1). In support of the latter possibility, type 11 collagen ((211) antibodies have been detected in the sera, synovial fluids, cartilage, and synovial tissues of some patients with RA (2-6). Recently, purified anti-CII antibody from an RA patient was found to passively transfer arthritis to mice (7), thereby providing evidence for the pathogenicity of this autoantibody in human arthritis.
In the experimental model of CII autoimmune arthritis, susceptibility to the induction of arthritis by murine CII autoantibody is linked to a predominant response of the complement-activating subclass of the IgG autoantibody, e.g., IgG2a in the DBN1 strain (8), and to its capacity to activate complement C5 to C5a when bound to cartilage (9). The studies reported herein were designed to assess directly the potential pathogenicity of human IgG autoantibodies to CII by analyzing their IgG subclass distribution and capacity to activate C5 to C5a when bound to human cartilage.