In order to examine the interactions between isolated rheumatoid factors (RFs) and cell nuclear antigens we have prepared 10 RFs by affinity chromatography against IgG coupled to Sepharose. Of these, seven cross reacted with cell nuclei on indirect immunofluorescence. The nuclear antigen appeared to be DNA histones by indirect immunofluorescence on rat liver, though on immunoblotting the rheumatoid factors also reacted with three non-histone polypeptides which were identified in the soluble fraction of nuclear extracts. We were unable to show any relationship between these polypeptides and rheumatoid arthritis nuclear antigen. These reactions represent a hitherto unrecognised phenomenon, which extends the range of antigens recognised by rheumatoid factors. We suggest that the immunopathogenic significance of RFs may not be restricted to their reactivity with IgG, and that non-histone nuclear proteins merit further investigation.
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