Rheumatoid arthritis sera react with a phage-displayed peptide selected bya monoclonal antibody to type II collagen that has homology to EBNA-1

Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies i nvolving probing of phage-displayed random peptide libraries with an antibo dy to type II collagen, CII-C1, me observed that among 17 phagotopes select ed 5 expressed peptides with homology with the sequence of EBNA-1. The resi dues in common were RLPFG. Hence we tested sera from 50 patients with RA, o f whom 26 had antibodies to native type II collagen, and 43 healthy control s, for reactivity by ELISA with a phagotope selected 4 times, which express ed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted wi th the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with w hich reactivity occurred in 78% of RA patients and 81% of controls. Evidenc e for molecular mimicry was not found insofar as the phagotope did not inhi bit reactivity of RA sera with EBNA-1 and CII-CI was not reactive with EBNA -1. We conclude that the reactivity of the RA sera with the phagotope is mo st likely due to the phagotope being a mimic of an epitope of type II colla gen for a proportion of RA sera.