Tape-Strip Proteomic Profiling of Atopic Dermatitis on Dupilumab Identifies Minimally Invasive Biomarkers

Front Immunol. 2020 Aug 6:11:1768. doi: 10.3389/fimmu.2020.01768. eCollection 2020.

Abstract

Tape-stripping is a minimally invasive approach for skin sampling that captures the cutaneous immune/barrier abnormalities in atopic dermatitis (AD). However, tape-strips have not been used to evaluate molecular changes with therapeutic targeting. In this study, we sought to characterize the proteomic signature of tape-strips from AD patients, before and after dupilumab therapy. Twenty-six AD patients were treated with every-other-week dupilumab 300 mg for 16 weeks. Tape-strips from lesional and non-lesional skin were collected before and after treatment, and analyzed with the Olink proteomic assay. Using criteria of fold-change>1.5 and FDR < 0.05, 136 proteins significantly decreased after dupilumab treatment, corresponding to an overall mean improvement of 66.2% in the lesional vs. non-lesional AD proteome. Significant decreases after dupilumab were observed in immune markers related to general inflammation (MMP12), Th2 (CCL13/CCL17), Th17/Th22 (IL-12B, CXCL1, S100A12), and innate immunity (IL-6, IL-8, IL-17C), while the Th1 chemokines CXCL9/CXCL10 remained elevated. Proteins related to atherosclerosis/cardiovascular risk (e.g., SELE/E-selectin, IGFBP7, CHIT1/ chitotriosidase-1, AXL) also significantly decreased after treatment. Dupilumab therapy suppressed AD-related immune biomarkers and atherosclerosis/cardiovascular risk proteins. Tape-strip proteomics may be useful for monitoring therapeutic response in real-life settings, clinical trials, and longitudinal studies for AD and beyond.

Keywords: atherosclerosis; atopic dermatitis; cardiovascular disease; dupilumab; olink; proteomics; tape-strips; targeted therapeutics.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / metabolism
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism
  • Dermatologic Agents / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteins / metabolism*
  • Proteome*
  • Proteomics*
  • Signal Transduction
  • Skin / drug effects*
  • Skin / immunology
  • Skin / metabolism
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Dermatologic Agents
  • Proteins
  • Proteome
  • dupilumab