ANTIGEN-BINDING DIFFERENCES BETWEEN SECRETED AND CELL-SURFACE EXPRESSED RHEUMATOID-FACTOR DERIVED FROM INFLAMED SYNOVIUM

Objective. Rheumatoid factor (RF) is the predominant autoantibody in r heumatoid arthritis (RA), but its role in the pathogenesis of RA remai ns unclear. We hypothesized that surface RF (sRF) expressed on antigen presenting B cells (B-APC) might have different binding specificities than secreted RF. Methods. We examined RF binding in a novel RF antig en capture enzyme linked immunoassay (ACE) that mimicked sRF binding, and compared it with a direct binding enzyme linked immunoassay (DBE) that mimicked secreted RF. Results. Significant differences in binding characteristics by the same rheumatoid synovial cell (RSC) derived mo noclonal RF (mRF) were observed between the ACE and the DBE. For examp le, several mRF that demonstrated the classical Ga binding pattern (bi nding to IgG1, 2, and 4) in the DBE showed considerable binding to sel ected IgG3 proteins in the ACE; and several mRF that bound only to rab bit IgG in the DBE bound to human IgG in the ACE. Conclusion. These RF reactivity differences may be attributed to conformational modificati ons in the RF and IgG molecules that expose different epitopes or alte red binding sites depending on the physical state of the antibody and/ or ant; en and may be important pathogenically.