학술논문

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.
Document Type
article
Source
The Journal of investigative dermatology. 140(1)
Subject
Th2 Cells
Skin
Humans
Staphylococcus aureus
Staphylococcal Infections
Dermatitis
Atopic
Disease Progression
Receptors
Interleukin-4
RNA
Ribosomal
16S
Cytokines
Placebos
Immunotherapy
Follow-Up Studies
Double-Blind Method
Female
Male
Antibodies
Monoclonal
Humanized
Infectious Diseases
Genetics
Clinical Research
Human Genome
Eczema / Atopic Dermatitis
Clinical Trials and Supportive Activities
Emerging Infectious Diseases
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
Clinical Sciences
Oncology and Carcinogenesis
Dermatology & Venereal Diseases
Language
Abstract
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.