Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology

Saakshi Khattri, Avner Shemer, Mariya Rozenblit, Nikhil Dhingra, Tali Czarnowicki, Robert Finney, Patricia Gilleaudeau, Mary Sullivan-Whalen, Xiuzhong Zheng, Hui Xu, Irma Cardinale, Cristina De Guzman Strong, Juana Gonzalez, Mayte Suárez-Fariñas, Jim G. Krueger, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Background Atopic dermatitis (AD) is the most common inflammatory disease. Evolving disease models link changes in epidermal growth and differentiation to TH2/TH22 cytokine activation. However, these models have not been tested by in vivo suppression of T-cell cytokines. Cyclosporine (CsA) is an immunosuppressant that is highly effective for severe disease, but its mechanism in AD skin lesions has not been studied. Objective We sought to establish the ability of a systemic immunosuppressant to modulate immune and epidermal alterations that form the pathogenic disease phenotype and to correlate changes with clinical improvement. Methods CsA's effects on AD skin pathology were evaluated by using gene expression and immunohistochemistry studies in baseline, week 2, and week 12 lesional and nonlesional biopsy specimens from 19 patients treated with 5 mg/kg/d CsA for 12 weeks. Results After 2 and 12 weeks of treatment, we observed significant reductions of 51% and 72%, respectively, in SCORAD scores. Clinical improvements were associated with significant gene expression changes in lesional but also nonlesional skin, particularly reductions in levels of TH2-, TH22-, and some TH17-related molecules (ie, IL-13, IL-22, CCL17, S100As, and elafin/peptidase inhibitor 3), and modulation of epidermal hyperplasia and differentiation measures. Conclusions This is the first study that establishes a relationship between cytokine activation and molecular epidermal alterations, as well as correlations between disease biomarkers in the skin and clinical improvement. The reversal of the molecular phenotype with CsA and the associated biomarkers can serve as a reference for the successful modulation of tissue inflammation with specific immune antagonists in future studies, contributing to the understanding of the specific cytokines involved in epidermal pathology.

Original languageEnglish
Pages (from-to)1626-1634
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Atopic dermatitis
  • S100 proteins
  • T cell
  • cyclosporine
  • epidermal abnormalities
  • immune

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