Genetic associations of variants of the high affinity receptor for immunoglobulin E in Wegener’s granulomatosis

Abstract

Immunoglobulin E (IgE) and the high affinity IgE receptor (FcepsilonRI) have been suggested to contribute to the pathogenesis of autoimmune disorders. Their role in Wegener's granulomatosis (WG) are, however, poorly recognized. We sought a genetic association between laboratory markers for the disease, i.e. anti-proteinase 3 antibodies (anti-PR3), anti-myeloperoxidase antibodies, anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), C3c and C4 complement components, and total serum IgE levels in WG subjects with common genetic variants of FcepsilonRI subunits. Anti-PR3 and CRP and serum IgE levels showed significant associations, while complement components tended to be associated, with -18483A > C and/or -344C > T FCER1A (FcepsilonRI alpha-subunit gene) polymorphisms. Moreover, a correlation between -109T > C FCER1B (FcepsilonRI beta-subunit gene) genotypes and serum IgE was observed. Both WG specific auto-antibodies and other blood inflammatory markers displayed correlations with serum total IgE levels and genetic variants of the high affinity receptor for this immunoglobulin. This observation suggests a functional relantionship of FcepsilonRI in the regulation of autoimmune response observed in WG.