Structural Characterization of Peptides That Bind Synovial Fluid Antibodies from RA Patients: A Novel Strategy for Identification of Disease-Related Epitopes Using a Random Peptide Library

Abstract

Phage epitope library technology has become a powerful tool for identifying determinants recognized by homogenous antibodies. Screening of human sera or fluids with random peptide phage libraries is a novel approach that can dissect common features at the amino acid level in individuals infected by the same etiological agent(s). In this study we have analyzed the specificity of antibodies in synovial fluids (SF) obtained from patients with rheumatoid arthritis (RA). We found that a high proportion of the peptides binding SF antibodies differ from those binding serum antibodies, suggesting that synovial B cells are expanded as a result of local antigen stimulation. When all the selected phages (enriched library) that bind the SF antibodies from a seropositive RA patient were further screened by the use of different SF antibodies with or without rheumatoid factor activity, we identified common SF antibody specificities (IRRSETPRA, RRRVRNSDT, PVSSTRGNM). Antibodies against these common specificities are also found in SF from other RA patients. Taken together, the present results open the possibility of defining the entire set of synovium antibody specificities and also common SF specificities between RA patients.