Adaptive immunity in rheumatoid arthritis: anticitrulline and other antibodies in the pathogenesis of rheumatoid arthritis.

PURPOSE OF REVIEW To describe recent progress concerning rheumatoid arthritis (RA)-associated autoantibodies, in particular antibodies to citrullinated proteins antigens. RECENT FINDINGS An increasingly diverse and RA-associated repertoire of antibodies has been defined over the last few years. These antibodies are preferentially, but not exclusively, reactive with posttranslationally modified antigens. Citrullinated antigens are the most common targets, but also other modifications including homocitrullination (carbamylation) are recognized. These antibodies display varying degrees of cross-reactivity, and both broadly cross-reactive and monoreactive antibodies are present. Progress, described in this review, has been made both concerning mechanisms behind the generation of these antibodies and concerning their effector functions. SUMMARY Several different triggering mechanisms are involved in forming an antibody repertoire that evolves before the onset of clinical disease, and where antibodies with different specificities may interact directly or indirectly with target organs in causing different arthritis-associated symptoms. The increasing understanding of the role of adaptive and specific immunity in RA creates opportunities for a new generation of interventions.