A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus

Lupus. 2015 Nov;24(13):1406-20. doi: 10.1177/0961203315596077. Epub 2015 Jul 22.

Abstract

Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

Keywords: Cutaneous lupus erythematosus; lupus erythematosus; peptides; peptidomics; photoprovocation.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Biopsy
  • Dose-Response Relationship, Radiation
  • Humans
  • Lupus Erythematosus, Cutaneous / blood
  • Lupus Erythematosus, Cutaneous / metabolism*
  • Lupus Erythematosus, Cutaneous / pathology
  • Peptides / blood*
  • Photosensitivity Disorders / blood
  • Photosensitivity Disorders / diagnosis
  • Photosensitivity Disorders / metabolism*
  • Skin / metabolism*
  • Skin / pathology
  • Skin / radiation effects
  • Ultraviolet Rays
  • beta 2-Microglobulin / metabolism
  • beta-Defensins / metabolism

Substances

  • Biomarkers
  • DEFB1 protein, human
  • Peptides
  • beta 2-Microglobulin
  • beta-Defensins