Effects of Omalizumab on FcεRI and IgE Expression in Lesional Skin of Bullous Pemphigoid

Abstract

Recent studies suggest an important role of immunoglobulin E (IgE) as an alternative pathogenic pathway in the development of bullous pemphigoid (BP), as the most frequent subepidermal blistering disease of the skin Use of IgE targeted therapies, such as omalizumab, has been shown promising in recent studies. The aim of this study was to assess the effect of omalizumab on FcεRI and IgE expression on circulating basophils and on lesional intradermal cells in BP to generate insight into the immunological effects of omalizumab in BP. We report two cases of BP patients treated with omalizumab. Efficacy of treatment was assessed clinically 4 months after initiation of the therapy. Lesional and non-lesional skin biopsies where taken before and 4 weeks after initiation of omalizumab therapy. In addition, FcεRI expression on circulating cells and IgE levels in serum and in the skin samples, as well as anti-BP180 and anti-BP230 in serum and eosinophils and basophils counts in blood were assessed before and during treatment. Both patients showed a marked improvement after 4 months, with no adverse effects. Down-regulation of FcεRI, IgE in lesional skin and on circulating basophils were observed in parallel with clinical improvement. The current case study supports the role of omalizumab in the treatment of a subset of BP patients. Our observations suggest that omalizumab represents a valuable therapeutic option in the management of BP patients. Its efficacy might be related to reduction in FcεRI+ and IgE+ basophils and intradermal cells.

TotalIgE, eosinophils, and interleukins 16,17A, and 23 correlations in severe bullous pemphigoid and treatment implications

“…The results of our study support the recently proposed theory of IgE being a pivotal immunoglobulin in BP, 14,17,18 along with peripheral blood eosinophils 8 and different soluble inflammatory response mediators 19 …”

Case Report: Combination of Omalizumab and Dupilumab for Recalcitrant Bullous Pemphigoid

“…However, in our patient there was no significantly increased serum IgE level. The observed beneficial effect of omalizumab in our patient with an excellent clinical response might be related to the sequestration of the free IgE, down-regulation of FcϵRI expression, dissociation of the IgE-FcϵRI complex and finally decrease in FcϵRI concentration on eosinophils and mast cells in affected tissues (6). Furthermore, the majority of patients with BP have an increased number of cells producing IL-4 and IL-13 in blood and lesional skin.…”

“…Furthermore, distinct immunosuppressive therapies may now pose additional risks in terms of COVID-19. Presence of tissue-bound and circulating anti-BP180 and anti-BP230 IgE autoantibodies in BP patients and findings in mouse models of BP have provided evidence that IgE autoantibodies have a pathogenicity role in BPs (2)(3)(4)(5)(6). Furthermore, type 2 pro inflammatory cytokines, including IL-4 and IL-13 contribute to tissue inflammation and damage in BP (7).…”

BP230 IgE autoantibodies in topical‐steroid‐resistant bullous pemphigoid

“…[22][23] The clinical efficacy of omalizumab has been proved with significant improvement of pruritus, erythematous, and bullous phenotypes in BP patients. 3,24,25 Interestingly, no decrease in BP180 and BP230 IgG autoantibodies was observed after 4 months, despite marked clinical improvement. 25 This could support the role of IgE autoantibodies participating in the pathogenesis of a subset of BP patients.…”

“…3,24,25 Interestingly, no decrease in BP180 and BP230 IgG autoantibodies was observed after 4 months, despite marked clinical improvement. 25 This could support the role of IgE autoantibodies participating in the pathogenesis of a subset of BP patients. However, the function of the anti-BP230 autoantibody in the pathogenesis of BP is largely unknown, although some evidence has suggested that anti-BP230 autoantibodies alone could cause disease.…”