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Antigen binding differences between secreted and cell surface expressed rheumatoid factor derived from inflamed
T P Kenny1, P Leider, P A Duong
1Department of Internal Medicine, School of Medicine, University of California, Davis 95616, USA.
Objective:
Rheumatoid factor (RF) is the predominant autoantibody in rheumatoid arthritis (RA). but its role in the pathogenesis of RA remains 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 antigen 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 monoclonal RF (mRF) were observed between the ACE and the DBE. For example, several mRF that demonstrated the classical Ga binding pattern (binding to IgG1, 2, and 4) in the DBE showed considerable binding to selected IgG3 proteins in the ACE; and several mRF that bound only to rabbit IgG in DBE bound to human IgG in the ACE.
Conclusion:
These RF reactivity differences may be attributed to conformational modifications in the RF and IgG molecules that expose different epitopes or altered binding sites depending on the physical state of the antibody and/or antigen and may be important pathogenically.