title: A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.
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.
authors.affiliation: Compound Development, Janssen Research & Development, LLC, USA CCalder2@its.jnj.com.
authors.forename: C
authors.initials: C
authors.lastname: Calderon
authors.affiliation: Formerly of Digilab BioVisioN GmbH, Germany; currently of Protagen AG, Dortmund, Germany.
authors.forename: H D
authors.initials: HD
authors.lastname: Zucht
authors.affiliation: Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center Mainz, Germany (research conducted at Department of Dermatology, University of Duesseldorf, Germany).
authors.forename: A
authors.initials: A
authors.lastname: Kuhn
authors.affiliation: Department of Dermatology and Venereology, Medical University of Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wozniacka
authors.affiliation: Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Poland.
authors.forename: J C
authors.initials: JC
authors.lastname: Szepietowski
authors.affiliation: Institution for Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Sweden; research conducted at Department of Dermatology, Danderyd Hospital, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: Department of Dermatology, Venerology and Allergology, University Hospital of Schleswig-Holstein, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weichenthal
authors.affiliation: Compound Development, Janssen Research & Development, LLC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Piantone
authors.affiliation: Formerly of Digilab BioVisioN GmbH, Germany; currently of Protagen AG, Dortmund, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Budde
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000097:blood*; D010787:Photosensitivity Disorders / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays; D001613:beta 2-Microglobulin / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D015415:Biomarkers; C406407:DEFB1 protein, human; D010455:Peptides; D001613:beta 2-Microglobulin; D023083:beta-Defensins
keywords: Cutaneous lupus erythematosus; lupus erythematosus; peptides; peptidomics; photoprovocation