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J Invest Dermatol. 2019 Jun 25. pii: S0022-202X(19)31789-0. doi: 10.1016/j.jid.2019.05.024. [Epub ahead of print]

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Author information

1
Department of Pediatrics, University of California San Diego, La Jolla, California, USA; Center for Microbial Ecology and Technology, Ghent University, Ghent, Belgium.
2
Department of Dermatology, University of California San Diego, La Jolla, California, USA.
3
Department of Pediatrics, University of California San Diego, La Jolla, California, USA; Departments of Computer Science & Engineering, University of California San Diego, La Jolla, California, USA; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
4
Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
5
Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
6
Sanofi-Genzyme, Cambridge, Massachusetts, USA.
7
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
8
Innovaderm Research, Inc., Montreal, Quebec, Canada.
9
Departments of Dermatology, Preventive Medicine, and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
10
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.
11
Department of Dermatology, Baylor University Medical Center, Dallas, Texas, USA.
12
Sanofi, Bridgewater, New Jersey, USA.
13
Department of Dermatology, University of California San Diego, La Jolla, California, USA. Electronic address: rgallo@ucsd.edu.

Abstract

Dupilumab is a fully human antibody to interleukin-4 receptor alpha that improves the signs and symptoms of moderate-to-severe atopic dermatitis. 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 atopic dermatitis 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 rRNA, 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 atopic dermatitis and biomarkers of type 2 immunity. We conclude that clinical improvement of atopic dermatitis that is mediated by interleukin-4 receptor alpha inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus. ClinicalTrials.gov identifier: NCT01979016.

PMID:
31252032
DOI:
10.1016/j.jid.2019.05.024
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