Studies on autoantigens in rheumatoid arthritis

This thesis describes the use of phage display for the isolation of autoantigens in rheumatoid arthritis. The potential of the technology is demonstrated by the isolation of an autoantigen, eukaryotic translation elongation factor 1a1 (eEF 1 (x 1) from a fibroblast cDNA library using rounds of selective enrichment with IgG from RA patients. Subsequently in order to isolate joint-specific antigens a phage-displayed cDNA library from rheumatoid pannus was generated and screened with analogous procedures. From the clones isolated, putative candidate autoantigens were identified. The presence of anti- eEF 1a1 autoantibodies in approximately 20% of patients with RA was confirmed and extended in larger panels of sera, and the finding of anti-eEF la1 shown to be relatively specific for RA. In contrast autoantibodies to the activation-induced negative regulator of T cells, CTLA-4 were not found in contrast to a previous report. The relevance of these findings for the use of antibodies in the diagnosis and prediction of disease characteristics in RA are discussed.