Fcγ-receptor 3B (FCGR3B) copy number variations in patients with eosinophilic granulomatosis with polyangiitis

To the Editor: Eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome) is a rare anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) characterized by asthma, rhinosinusitis, eosinophilia, and involvement of different organs.1 Two major disease subsets, defined as vasculitic and eosinophilic, have been identified. In the former subset clinical manifestations caused by small-vessel vasculitis (eg, peripheral neuropathy, glomerulonephritis, and purpura) predominate, whereas the latter subset more commonly shows manifestations related to eosinophil infiltration (eg, cardiomyopathy and gastroenteritis). ANCAs, which are detectable in 40% of patients, are associated with the vasculitic subset.2 The genetic basis of EGPA is poorly investigated. Genetic associations include HLA-DRB4 and IL10 single nucleotide polymorphisms.3, 4 In addition to single nucleotide polymorphisms, copy number variations (CNVs) represent a significant source of genetic heterogeneity. In patients with autoimmune diseases, CNVs involving Fcγ receptor (FcγR) genes were extensively investigated. FcγRs bind the IgG constant domain and regulate mobilization of macrophages, natural killer cells, and neutrophils to sites of immune complex deposition. Fcγ-receptor 3B (FCGR3B) deficiency (ie, low copy number [CN]) was shown to predispose to systemic autoimmune diseases.5 We investigated whether FCGR3B CNVs confer susceptibility to EGPA and explored their associations with disease phenotypes. We studied 126 patients with EGPA and 249 healthy white subjects. The diagnosis of EGPA fulfilled the American College of Rheumatology 1990 Criteria and the Chapel Hill Consensus Conference definition of EGPA.6, 7 The Ethics Committee of Parma Hospital approved the study; all participants signed a written informed consent form. FCGR3B CNs were determined from genomic DNA by using a TaqMan CN real-time PCR assay (Life Technologies, Grand Island, NY); RNaseP (Life Technologies) was used as a reference assay, and both target and reference samples were run in a single tube. All samples were tested in triplicate. For further details, see the Methods section and Fig E1, Fig E2 in this article's Online Repository at www.jacionline.org.