Biological and Clinical Response to Omalizumab in a Patient with Bullous Pemphigoid

Menzinger, Sébastien; Kaya, Gürkan; Schmidt, Enno; Fontao, Lionel; Laffitte, Emmanuel

doi:10.2340/00015555-2845

Cited by 19 publications

(10 citation statements)

References 14 publications

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“…Frequent detection of high levels of IgE autoantibodies against BP180 and BP230, increased serum levels of IgE and the reported beneficial effect of anti-IgE therapy in small case series support the idea that IgE autoantibodies are involved in BP pathogenesis (1, 2, 5, 10, 12, 15–18, 22–24). However, the pathogenicity of IgE autoantibody in BP remains unclear (25). It is thought that IgE autoantibodies directed against the extracellular domain of BP180 are first bound to FcεRI on mast cells and eosinophils.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…In a number of case reports and case series, excellent efficacy of treatment with omalizumab has been shown in BP patients ( 133 – 140 ). While these findings are highly suggestive of a pathogenic role for auto-IgE in BP, controlled clinical trials with omalizumab in BP are necessary to prove the efficacy of anti-IgE treatment and thus of the relevance of auto-IgE in BP.…”

Section: What Do We Know About the Relevance Of Ige Autoantibodies Inmentioning

confidence: 99%

Immunoglobulin E-Mediated Autoimmunity

et al. 2018

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The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

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“…Eosinophil-derived IL-31 may possibly participate in the trafficking of basophils to lesional tissues affected by BP and this may further be supported by IL-31-induced CCL26 release from eosinophils (5). Furthermore, there are several case reports of successful therapy of BP using omalizumab, suggesting potential basophil involvement (54–56). However, Freire et al recently showed that the mast cells and eosinophils make up most of the IgE-expressing cells in BP skin (57) and both cell types are widely reported to participate in various autoimmune skin diseases [reviewed in (58, 59)].…”

Section: Il-31 In Autoimmune Skin Diseasesmentioning

confidence: 99%

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

2019

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Many autoimmune skin diseases, such as bullous pemphigoid (BP), psoriasis and certain types of chronic urticaria, are associated with intensive pruritus. While histamine and neuropeptides have previously been ascribed to play a role in itch that accompanies these diseases, recent evidence suggests that the pruritogenic cytokine interleukin (IL)-31 is a major driver of pruritic responses. IL-31 was originally shown to be produced by activated helper T cells, particularly Th2 cells, mast cells, macrophages and dendritic cells. However, more recent evidence demonstrated that eosinophils are a major source of this cytokine too, particularly in bullous pemphigoid. Basophils have also been shown to express the cytokine which, through autocrine action, strongly supports the production of other Th2-type cytokines from these cells. These investigations suggest that the dynamic recruitment of eosinophils and basophils in some autoimmune skin diseases could play an important role in the severity of IL-31-mediated itch. Furthermore, these studies suggest that IL-31, in addition to its pruritic actions, also has potential immunomodulatory roles in terms of supporting Th2-type immunity, which often underpins IgE-associated autoimmune diseases (such as bullous pemphigoid and urticaria) as well as allergies. While the role of IL-31 in psoriasis remains to be clarified, current evidence shows that this cytokine plays a major role in BP, chronic spontaneous urticaria and dermatomyositis. This suggests potential use of IL-31 receptor-blocking therapeutic approaches (e.g., Nemolizumab) for the treatment of IL-31-associated disorders.

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Biological and Clinical Response to Omalizumab in a Patient with Bullous Pemphigoid

Cited by 19 publications

References 14 publications

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

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

Immunoglobulin E-Mediated Autoimmunity

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

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