Recognition by anti-Fab antibodies in rheumatoid arthritis of structure(s) widely distributed on human Fab molecules.

Anti-Fab antibodies (aFABA) of restricted clonality and acidic spectrotypes were isolated from the sera of patients with rheumatoid arthritis (RA). These aFABA reacted with multiple populations of pooled human Fab molecules, which had been charge separated by chromatofocusing techniques (CF), indicating that the structures recognized by these aFABA were present on a polyclonal population of Fab molecules. The structures were also widely distributed among the Fab repertoires of normal individuals, as well as individual autologous and heterologous RA patients. Thus, the aFABA did not appear to recognize highly restricted epitope(s), i.e. a private idiotope, limited in its expression to RA individuals. The determinants of the Fab molecules recognized by affinity purified aFABA could be defined by linear and/or conformational structures, depending upon the individual from which the aFABA were isolated. Additionally, some of the affinity purified aFABA also reacted with Fc fragments, suggesting the presence of epibody-like autoantibodies in this population. Lastly, size analysis of the circulating IgG4 aFABA complexes indicated that these autoantibodies were not complexed with intact IgG, but rather with a molecule of 40-60 kDa, further suggesting the potential for these autoantibodies to react with multiple antigens.