Fcγ receptor polymorphisms in Wegener's granulomatosis: Risk factors for disease relapse

Abstract

Objective. Several studies have recently identified polymorphisms of receptors for the Fc fragment of IgG (FcγR) as genetic factors influencing susceptibility to multiple autoimmune and infectious diseases. This genetic predisposition could also influence the expression of Wegener's granulomatosis (WG), a systemic autoimmune disease with chronic nasal carriage of Staphylococcus aureus as an important risk factor for disease relapses. Therefore, we analyzed 3 functional FcγR polymorphisms from 91 patients with WG and 154 controls for a possible relationship with disease expression and occurrence of relapses. Methods. FcγR phenotypes were determined using amplification of FcγR-genomic regions in allotype-specific polymerase chain reactions. Of particular interest in the analysis were 2 allotypic forms of FcγRIIa (R131 or H131) and 2 allotypic forms of FcγRIIIa (V158 or F158), all of which are functionally different. Results. Analysis of FcγR phenotypes demonstrated that patients with WG were more prone to disease relapse in the first 5 years after diagnosis if they were homozygous for both the R131 form of FcγRIIa and the F158 form of FcγRIIIa (relative risk 3.3, 95% confidence interval 1.6-6.8). These polymorphisms are both associated with decreased FcR-mediated clearance, which may be relevant to the chronic nasal carriage of S aureus. Conclusion. Both the R/H131 polymorphism of FcγRIIa and the V/F158 polymorphism of FcγRIIIa represent heritable risk factors for the development of disease relapses in WG.