Benralizumab在特应性皮炎患者皮肤病变中减少il - 5r α-承载细胞

IF 4 2区 医学 Q2 ALLERGY
Christiane E Whetstone, Ruth P Cusack, Emma L Price, Karen J Howie, Caitlin Stevens, Dhuha Al-Sajee, Suzanne Beaudin, Jennifer Wattie, Nadia Alsaji, Abbey Schlatman, Vanessa Luk, Paul M O'Byrne, Mark D Inman, Roma Sehmi, Hermenio Lima, Gail M Gauvreau
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引用次数: 0

摘要

背景:特应性皮炎(AD)是一种以组织嗜酸性粒细胞增多和瘙痒为特征的慢性炎症性皮肤病。我们评估了benralizumab对AD患者皮肤炎症标志物的嗜酸性粒细胞去除的影响。方法:在口服抗炎药物4周的洗脱期后,20名中度至重度AD患者完成了一项随机、双盲、安慰剂对照平行组研究,将3次剂量的benralizumab皮下注射与安慰剂比较。分别于治疗前和治疗后28天和65天收集病变和未受影响的皮肤活检,定量测定乳头状真皮中嗜酸性粒细胞和携带il - 5r α的细胞。在整个研究过程中进行了表皮厚度、海绵状组织、中性粒细胞和淋巴细胞浸润的组织学测量,以及EASI、SCORAD、IGA、DLQI和POEM的临床评分。使用Mann-Whitney u检验比较安慰剂组和贝那利单抗治疗组的结果。结果:与安慰剂相比,Benralizumab可降低病变和未受影响皮肤中的IL-5Rα+细胞和MBP+ EG2+嗜酸性粒细胞(p)结论:Benralizumab治疗可显著抑制中重度AD患者病变皮肤中MBP+嗜酸性粒细胞和嗜碱性粒细胞的积累。然而,组织学和临床结果缺乏改善,表明其他炎症途径是严重特应性皮炎病理生物学的核心。试验注册:(ClincialTrials.gov号码,NCT03563066)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Benralizumab Depletes IL-5Rα-Bearing Cells in Skin Lesions of Patients With Atopic Dermatitis.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by tissue eosinophilia and itch. We evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in the skin of patients with AD.

Methods: After a 4-week washout from oral anti-inflammatory medications 20 patients with moderate to severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses q4wk 30 mg subcutaneous benralizumab to placebo. Lesional and unaffected skin biopsies were collected before and after 28 and 65 days of treatment, respectively, for quantification of eosinophils and IL-5Rα-bearing cells in papillary dermis. Histological measurements of epidermal thickness, spongiosis, neutrophilic and lymphocytic infiltration, as well as clinical scores EASI, SCORAD, IGA, DLQI, and POEM were conducted throughout the study. Outcomes were compared between placebo and benralizumab treatment groups using a Mann-Whitney U-test.

Results: Benralizumab, compared to placebo, reduced IL-5Rα+ cells and MBP+ EG2+ eosinophils in lesions and unaffected skin (p < 0.05). In skin lesions, benralizumab reduced MBP+ eosinophils and basophils but had no effect on eosinophil progenitor (EoP; CD34+ IL-5Rα+) or mast cell numbers. There was no change in other skin histological measurements or IGA scoring of the observational lesion, nor improvement in clinical scores.

Conclusion: Benralizumab treatment significantly inhibited accumulation of MBP+ eosinophils and basophils in lesional skin of patients with moderate to severe AD. However, a lack of improvement in histological and clinical outcomes suggests that other inflammatory pathways are central to the pathobiology of severe atopic dermatitis.

Trial registration: (ClincialTrials.gov number, NCT03563066).

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来源期刊
Clinical and Translational Allergy
Clinical and Translational Allergy Immunology and Microbiology-Immunology
CiteScore
7.50
自引率
4.50%
发文量
117
审稿时长
12 weeks
期刊介绍: Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.
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