IgM and IgA in addition to IgG autoantibodies against FceRIα are frequent and associated with disease markers of chronic spontaneous urticaria

Background IgG autoantibodies against the high-affinity IgE receptor, FceRI alpha, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known whether such patients also exhibit IgM or IgA autoantibodies against FceRI alpha. To address this question we developed an ELISA to assess serum levels of IgG, IgM, and IgA autoantibodies against FceRI alpha and investigated whether their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST). Methods Serum samples of 35 CSU patients (25 ASST-positive) and 52 healthy control individuals were analyzed using a newly developed competitive ELISA for IgG, IgM, and IgA autoantibodies to FceRI alpha. Results One in four CSU patients (8/35, 24%) had elevated serum levels of IgG-anti-FceRI alpha compared with (3/52, 6%) healthy controls. More than half of patients had IgM (21/35, 60%) and IgA (20/35, 57%) vs (3/52, 5%) each in healthy controls. Elevated IgM, but not IgG or IgA, autoantibodies were significantly more frequent in ASST-positive CSU patients (18/25, 72%) compared with ASSTnegative patients (3/10, 33%,P = .022). Also, elevated levels of IgM-anti-FceRI alpha, but not of IgG or IgA against FceRI alpha, were linked to low blood basophil (r = .414,P = .021) and eosinophil (r = .623,P < .001) counts. Conclusions Increased serum levels of IgM-anti-FceRI alpha are common in patients with CSU and linked to features of autoimmune CSU. The role and relevance of autoantibodies to FceRI alpha in CSU can and should be further characterized in future studies, and our novel assay can help with this.