ANALYSIS OF FC-GAMMA-RII GENE POLYMORPHISMS IN WEGENERS GRANULOMATOSIS

Fc gamma receptors (Fc gamma Rs) are potent initiators of proinflammat ory reactions and tissue injury programs through the oxidative burst, degranulation and the production of a variety of proinflammatory cytok ines, Direct experimental evidence indicates that translocation of ANC A target from intracellular granules to the neutrophil membrane and su bsequent binding of ANCA enables Fc gamma R-mediated neutrophil activa tion, In the presence of ANCA, these data provide a framework from whi ch to understand the importance of ANCA class, subclass, and titer in Wegener's granulomatosis and other ANCA-positive vasculitides. The wel l-characterized and functionally important alleles of neutrophil Fc ga mma R (Fc gamma RIIa-H131/R131 and Fc gamma RIIIb-NA1/NA2) are possibl e inheritable genetic elements that may alter disease severity and/or phenotype.