Dupilumab Therapy Improves Stratum Corneum Hydration and Skin Dysbiosis in Patients With Atopic Dermatitis
이승주, 김송이, 신경오, 박경호, 이상은,
소속 상세정보
이승주 ( Lee Seung-Ju )
Yonsei University College of Medicine Gangnam Severance Hospital Department of Dermatology
김송이 ( Kim Song-Ee )
Yonsei University College of Medicine Gangnam Severance Hospital Department of Dermatology
신경오 ( Shin Kyong-Oh )
Hallym University Department of Food Science and Nutrition
박경호 ( Park Kyung-Ho )
Hallym University Department of Food Science and Nutrition
이상은 ( Lee Sang-Eun )
Yonsei University College of Medicine Gangnam Severance Hospital Department of Dermatology
Abstract
Purpose: We aimed to investigate the effects of dupilumab on 1) the permeability and antimicrobial barrier, 2) the composition of the skin microbiome, and 3) the correlation between changes in skin barrier properties and microbiota in atopic dermatitis (AD) patients.
Methods: Ten patients with severe AD were treated with dupilumab for 12 weeks. Disease severity was assessed using the Eczema Area and Severity Index (EASI). Skin barrier function was evaluated by measuring transepidermal water loss, stratum corneum (SC) hydration, and pH. The following parameters were analyzed in the pre- and post-treatment SC samples; 1) skin microbiota using 16S rRNA gene sequencing, 2) lipid composition using mass spectrometry, and 3) human β-defensin 2 (hBD-2) expression using quantitative reverse transcription polymerase chain reaction.
Results: SC hydration levels in the lesional and non-lesional skin increased after 12-week dupilumab therapy (24.2%, P < 0.001 and 59.9%, P < 0.001, respectively, vs. baseline) and correlated with EASI improvement (r = 0.90, P < 0.001 and r = 0.85, P = 0.003, respectively). Dupilumab increased the long-chain ceramide levels in atopic skin (118.4%, P = 0.028 vs. baseline) that correlated with changes in SC hydration (r = 0.81, P = 0.007) and reduced the elevated hBD-2 messenger RNA levels (?15.4%, P = 0.005 vs. baseline) in the lesional skin. Dupilumab decreased the abundance of Staphylococcus aureus. In contrast, the microbial diversity and the abundance of Cutibacterium and Corynebacterium species increased, which were correlated with an increase in SC hydration levels (Shannon diversity, r = 0.71, P = 0.027; Cutibacterium, r = 0.73, P = 0.017; Corynebacterium, r = 0.75, P = 0.012). Increased abundance of Cutibacterium species was also correlated with EASI improvement (r = 0.68, P = 0.032).
Conclusions: Th2 blockade-induced normalization of skin microbiome in AD patients is associated with increased SC hydration.
키워드
Atopic dermatitis; dupilumab; stratum corneum hydration; microbiota; ceramides; Staphylococcus aureus; Cutibacterium
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