Analysis of FcgammaRII gene polymorphisms in Wegener's granulomatosis.

Fcgamma receptors (FcgammaRs) are potent initiators of proinflammatory reactions and tissue injury programs through the oxidative burst, degranulation and the production of a variety of proinflammatory cytokines. Direct experimental evidence indicates that translocation of ANCA target from intracellular granules to the neutrophil membrane and subsequent binding of ANCA enables FcgammaR-mediated neutrophil activation. In the presence of ANCA, these data provide a framework from which to understand the importance of ANCA class, subclass, and titer in Wegener's granulomatosis and other ANCA-positive vasculitides. The well-characterized and functionally important alleles of neutrophil FcgammaR (FcgammaRIIa-H131/R131 and FcgammaRIIIb-NA1/NA2) are possible inheritable genetic elements that may alter disease severity and/or phenotype.