Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

J Am Acad Dermatol. 2017 May;76(5):847-855.e5. doi: 10.1016/j.jaad.2016.12.021. Epub 2017 Mar 1.

Abstract

Background: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

Objective: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

Methods: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups.

Results: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3.

Limitations: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response.

Conclusion: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

Keywords: CD8; CXCL10; CXCL9; autoimmunity; biomarkers; biopsy; blisters; inflammatory skin disease; suction blister; vitiligo.

Publication types

  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • Blister / metabolism*
  • CD8-Positive T-Lymphocytes
  • Case-Control Studies
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / metabolism
  • Chemokine CXCL9 / metabolism*
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • ROC Curve
  • Receptors, CXCR3 / metabolism*
  • Suction
  • Vitiligo / immunology*
  • Vitiligo / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • CXCL10 protein, human
  • CXCL11 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Receptors, CXCR3
  • Interferon-gamma