THE MECHANISM OF AUTOANTIBODY FORMATION TO CARTILAGE IN RHEUMATOID-ARTHRITIS - POSSIBLE CROSS-REACTION OF ANTIBODIES TO DIETARY COLLAGENS WITH AUTOLOGOUS TYPE-II COLLAGEN

In order to study the mechanism of autoantibody formation to type II c ollagen in rheumatoid arthritis (RA), IgG and IgA antibodies in sera f rom 259 RA patients and 285 non-RA controls were evaluated for their s pecificity as to collagen type (I and II) and species (chick, bovine, and porcine) using an improved enzyme-linked immunosorbent assay. IgG and IgA anti-type II collagen antibodies were commonly found in both R A (IgG, 41%; and IgA, 45%) and non-RA (IgG, 36%; and IgA, 31%) sera. B oth IgG and IgA collagen antibodies were highly reactive with one or m ore heterologous type II or type I collagen; however, approximately 35 % of IgG and 50% of IgA antibody-positive sera from both RA patients a nd non-RA controls crossreacted with human type IT collagen (HII) to s ome degree. However, no antibodies specific to HII were observed in ei ther RA or control sera. In individual patient sera, IgG and IgA antib odies had identical collagen-type and species specificities. Important ly, IgG anti-HII antibodies purified from RA sera by affinity chromato graphy reacted equally with human, chick and bovine type II collagens, suggesting reactivity with conserved epitopes shared by all three spe cies. In contrast, purified IgG anti-HII antibodies from non-RA contro l sera commonly lacked reactivity with one or the other of the heterol ogous type II collagens, suggesting reactivity limited to epitopes sha red by HII and only one of the heterologous type II collagens. These d ata suggest that dietary collagens could elicit circulating IgG and Ig A anti-collagen antibodies that cross-react with autologous type II co llagen. Also the epitope specificity of IgG autoantibodies may be rele vant to the pathogenesis of RA. (C) 1996 Academic Press, Inc.