Department of Pediatrics, University of California San Diego, La Jolla, California, USA; Center for Microbial Ecology and Technology, Ghent University, Ghent, Belgium.
Department of Dermatology, University of California San Diego, La Jolla, California, USA.
J Invest Dermatol. 2020 Jan;140(1):191-202.e7. doi: 10.1016/j.jid.2019.05.024. Epub 2019 Jun 25.
Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus.
度普利尤单抗是一种针对白细胞介素-4 受体 α 的全人源单克隆抗体,可改善中重度特应性皮炎(AD)的体征和症状。为了确定度普利尤单抗对金黄色葡萄球菌定植和皮肤微生物多样性的影响,对 54 例中重度 AD 患者进行了一项双盲、安慰剂对照研究,患者随机(1:1)接受度普利尤单抗(每周 200mg)或安慰剂治疗 16 周,采集皮损和非皮损部位的拭子,提取细菌 DNA,通过 16S 核糖体 RNA 的 DNA 测序分析微生物多样性和金黄色葡萄球菌的相对丰度,并通过定量 PCR 测量金黄色葡萄球菌的绝对丰度。治疗前,皮损部位的微生物多样性低于非皮损部位,金黄色葡萄球菌的总体丰度高于非皮损部位。在度普利尤单抗治疗期间,微生物多样性增加,金黄色葡萄球菌的丰度下降。非皮损和皮损部位均可见明显变化。度普利尤单抗治疗期间金黄色葡萄球菌丰度下降与 AD 的临床改善和 2 型免疫标志物相关。我们得出结论,由白细胞介素-4 受体 α 抑制介导的 AD 临床改善,以及随后的 2 型炎症抑制,与微生物多样性增加和金黄色葡萄球菌丰度降低相关。