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

Background IgG autoantibodies against the high-affinity IgE receptor, FcɛRIα, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known whether such patients also exhibit IgM or IgA autoantibodies against FcɛRIα. To address this question we developed an ELISA to assess serum levels of IgG, IgM, and IgA autoantibodies against FcɛRIα 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 FcɛRIα. Results One in four CSU patients (8/35, 24%) had elevated serum levels of IgG-anti-FcɛRIα 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-FcɛRIα, but not of IgG or IgA against FcɛRIα, were linked to low blood basophil (r = .414,P = .021) and eosinophil (r = .623,P < .001) counts. Conclusions Increased serum levels of IgM-anti-FcɛRIα are common in patients with CSU and linked to features of autoimmune CSU. The role and relevance of autoantibodies to FcɛRIα in CSU can and should be further characterized in future studies, and our novel assay can help with this

A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches

Non-steroidal anti-inflammatory drugs (NSAIDs) that act as cyclo-oxygenase (COX) inhibitors are commonly used in the treatment of a range of headache disorders, although their mechanism of action is unclear. Indomethacin is of particular interest given its very special effect in some primary headaches. Here the in vivo technique of intravital microscopy in rats has been utilised as a model of trigeminovascular nociception to study the potential mechanism of action of indomethacin. Dural vascular changes were produced using electrical (neurogenic) dural vasodilation (NDV), calcitonin gene-related peptide (CGRP) induced dural vasodilation and nitric oxide (NO) induced dural vasodilation using NO donors. In each of these settings the effect of intravenously administered indomethacin (5 mg kg−1), naproxen (30 mg kg−1) and ibuprofen (30 mg kg−1) was tested. All of the tested drugs significantly inhibited NDV (between 30 and 52%). Whilst none of them was able to inhibit CGRP-induced dural vasodilation, only indomethacin reduced NO induced dural vasodilation (35 ± 7%, 10 min post administration). We conclude NSAIDs inhibit release of CGRP after NDV without an effect on CGRP directly. Further we describe a differentiating effect of indomethacin inhibiting nitric oxide induced dural vasodilation that is potentially relevant to understanding its unique action in disorders such as paroxysmal hemicrania and hemicrania continua