New rheumatoid arthritis genetic factor and C5 serum level.

摘要

There is a significant body of evidence suggesting that complement activation plays an important role in the maintenance of the polyarticular chronic synovitis characteristic of rheumatoid arthritis (RA).1 Recently, a novel RA genetic risk factor was described, involving allelic polymorphisms on the chromosome 9, in the intergenic region between complement factor 5 (C5) and tumour necrosis factor receptor-associated factor 1 (TRAF'I) genes." The new genetic factor, detected in RA case-control studies for anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor positive (RP+) RA in North American, Swedish and Dutch populations,2 3 was confirmed by linkage in a family based study from a European Caucasian population.4 The RA pathophysiological mechanism implicating these polymorphisms remains unknown, but, as they are in linkage disequilibrium with the 3'end of the C5 gene, they could affect yet unknown regulatory elements of the gene and influence C5 synthesis. Indeed, a significant role of C5 in RA pathogenesis is supported by a variety of human and animal studies.5 6 Moreover, studies in experimental models suggested that C5 plays an important role in the development of murine RA.7"9