Whetstone Christiane E, Cusack Ruth P, Price Emma, Howie Karen, Stevens Catie, Al-Sajee Dhuha, Beaudin Sue, Wattie Jennifer, Alsaji Nadia, Schlatman Abbey, Luk Vanessa, Ju Xiaotian, O'Byrne Paul, Inman Mark, Sehmi Roma, Lima Hermenio, Gauvreau Gail M
Department of Medicine, Division of Respirology, McMaster University, Hamilton, Ontario, Canada.
Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada.
J Allergy Clin Immunol Glob. 2024 Jul 22;3(4):100310. doi: 10.1016/j.jacig.2024.100310. eCollection 2024 Nov.
Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia.
In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge.
A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11). Allergen and saline control intradermal challenges were conducted before and after treatment, with skin biopsy samples collected 24 hours after challenge. Early and late cutaneous responses were measured by skin wheal size. Levels of eosinophils and IL-5 receptor-α-bearing cells, including eosinophil progenitor (EoP) cells, basophils, and mast cells, in papillary dermis were measured by immunofluorescence microscopy, and levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood were measured by flow cytometry. Outcomes were compared between the placebo and benralizumab treatment groups by using the Mann-Whitney test.
Benralizumab reduced eosinophil counts in the blood ( < .0001) and allergen-challenged skin, as measured by hematoxylin and eosin staining and eosinophil cationic protein antibody concentration ( < .05). Benralizumab lowered the levels of EoP cells, mast cells, and basophils in the skin, as well as the levels of EoP cells, hematopoietic progenitor cells, and type 2 innate lymphoid cells in the blood (all < .05). There was a trend toward improvement in the early cutaneous response ( = .095) but no effect on the late cutaneous response.
In patients with moderate-to-severe AD, benralizumab treatment significantly inhibited accumulation of eosinophils and other IL-5 receptor-α-expressing cells in the papillary dermis after intradermal allergen challenge. Targeting IL-5 receptor-α-positive cells did not modulate the size of the allergen-induced skin wheal (ClincialTrials.gov identifier NCT03563066).
特应性皮炎（AD）是一种以组织嗜酸性粒细胞增多为特征的皮肤屏障功能障碍。
在AD患者中，我们评估了使用贝那利珠单抗清除嗜酸性粒细胞对皮内过敏原激发后皮肤炎症标志物的影响。
共有20例中度至重度AD患者完成了一项随机、双盲、安慰剂对照平行组研究，比较每4周皮下注射3剂贝那利珠单抗（各30 mg，n = 9）与安慰剂（n = 11）的效果。在治疗前后进行过敏原和生理盐水对照皮内激发试验，并在激发后24小时采集皮肤活检样本。通过皮肤风团大小测量早期和晚期皮肤反应。通过免疫荧光显微镜测量乳头真皮中嗜酸性粒细胞和表达IL-5受体-α的细胞（包括嗜酸性粒细胞祖细胞（EoP）、嗜碱性粒细胞和肥大细胞）的水平，并通过流式细胞术测量血液中EoP细胞、造血祖细胞和2型天然淋巴细胞的水平。使用Mann-Whitney检验比较安慰剂组和贝那利珠单抗治疗组的结果。
通过苏木精和伊红染色以及嗜酸性粒细胞阳离子蛋白抗体浓度测量，贝那利珠单抗降低了血液（P <.0001）和过敏原激发皮肤中的嗜酸性粒细胞计数（P <.05）。贝那利珠单抗降低了皮肤中EoP细胞、肥大细胞和嗜碱性粒细胞的水平，以及血液中EoP细胞、造血祖细胞和2型天然淋巴细胞的水平（均P <.05）。早期皮肤反应有改善趋势（P =.095），但对晚期皮肤反应无影响。
在中度至重度AD患者中，贝那利珠单抗治疗显著抑制皮内过敏原激发后乳头真皮中嗜酸性粒细胞和其他表达IL-5受体-α的细胞的积聚。靶向IL-5受体-α阳性细胞并未调节过敏原诱导的皮肤风团大小（ClinicalTrials.gov标识符NCT03563066）。
