The structure and origin of rheumatoid factors

The recently determined X-ray crystal structure of a human rheumatoid facto r Fab bound to IgG Fe provides the basis of a new hypothesis for the origin of these autoantibodies in rheumatoid arthritis. The observation that Fe i s bound outside the conventional antigen combining site suggests it novel f orm of crossreactivity with simultaneous binding of another antigen, potent iated by somatic mutation. This article discusses the implications for the induction of these autoantibodies.