Eosinophils as putative therapeutic targets in bullous pemphigoid

Simon, Dagmar; Borradori, Luca; Simon, Hans‐Uwe

doi:10.1111/exd.13416

Cited by 28 publications

(23 citation statements)

References 97 publications

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“…Eosinophils are present in skin lesions and are often increased in peripheral blood, and recent studies indicate that they contribute to pathogenesis ( 86 ). Targeting eosinophils may therefore represent a future therapeutic alternative for this disease ( 87 ). A 3-month phase 2 placebo-controlled trial evaluating the efficacy of monthly infusions of mepolizumab (750 mg) in adult patients with active bullous pemphigoid has recently been completed and results should be available shortly.…”

Section: Anti-il-5 Treatment In Other Inflammatory Disorders Associatmentioning

confidence: 99%

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

2018

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Improved understanding of the contribution of eosinophils to various chronic inflammatory conditions, most notably allergic asthma, has encouraged development of monoclonal antibodies specifically targeting mediators and surface receptors involved in eosinophil expansion and activation. The pivotal role of interleukin-5 (IL-5) in eosinophil biology, its high specificity for this leukocyte subset, and its involvement in the majority of eosinophilic conditions make it a very enticing target for treatment of eosinophil-mediated disorders. Two types of antibodies have been developed to target eosinophils: antibodies against IL-5 (mepolizumab and reslizumab), and an antibody against the IL-5-receptor-alpha-chain (IL-5Rα) (benralizumab). Both types of antibodies prevent IL-5 from engaging its receptor and in addition, anti-IL-5Rα antibodies induce target-cell lysis. They have been shown to reduce circulating eosinophil counts rapidly in humans with various disorders. Herein, a brief overview of the role of IL-5 in eosinophil biology will be presented, followed by a description of the development and characteristics of antibodies targeting IL-5 or its receptor. Results of clinical trials evaluating the efficacy and safety of these new antibodies in diseases (other than eosinophilic asthma) with prominent tissue eosinophilia are reviewed, followed by safety considerations and potential future applications.

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Section: Anti-il-5 Treatment In Other Inflammatory Disorders Associatmentioning

confidence: 99%

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

2018

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“…Third, eosinophils are capable to induce dermal‐epidermal separation in an ex vivo model of BP. These aspects, as well as their potential therapeutic implications, are carefully reviewed and discussed here by Simon et al …”

Section: Pd Model Systems and Their Use In Basic And Translational Rementioning

confidence: 99%

New insights into pemphigoid diseases

Antonicelli

Ludwig

2017

Experimental Dermatology

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“…Their impact on biological processes is likely mediated primarily by their cytoplasmic granules. These granules are classified as primary, secondary, small granules, and lipid bodies ( 54 ). Secondary granules contain four toxic basic proteins: the major basic protein (MBP), eosinophil peroxidase (EPX), eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP).…”

Section: Introduction To Eosinophilsmentioning

confidence: 99%

“…ECP can also lead to epithelial and neuronal apoptosis ( 59 – 61 ). MBP toxicity is mediated by affecting the charge of cellular surface membranes resulting in disruption and altered permeability leading to cellular injury ( 54 , 62 ). Eosinophils are also implicated in the production of various cytokines, chemokines, lipid mediators, and superoxide.…”

Section: Introduction To Eosinophilsmentioning

confidence: 99%

The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease

et al. 2018

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Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease.

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Eosinophils as putative therapeutic targets in bullous pemphigoid

Cited by 28 publications

References 97 publications

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

New insights into pemphigoid diseases

The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease

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