Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders

Jannie M.B. Sand*, Patricia Lamy, Pernille Juhl, Anne Sofie Siebuhr, Line V. Iversen, Arkadiusz Nawrocki, Martin R. Larsen, Robyn T. Domsic, Nathalie Franchimont, Juan Chavez, Morten A. Karsdal, Diana J. Leeming

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients with systemic sclerosis (SSc), whereas reduced levels in the airways have been related to asthma. This indicates that type VII collagen plays an important part in upholding tissue integrity and that its remodeling may lead to pathological states. The aim of this study was to investigate the role of type VII collagen remodeling in fibroproliferative disorders. We produced monoclonal antibody targeting a specific fragment of type VII collagen (C7M) released to the systemic circulation and developed a neo-epitope specific competitive enzyme-linked immunosorbent assay (ELISA). Biological relevance was evaluated in serum from patients with SSc or chronic obstructive pulmonary disease (COPD). The C7M ELISA was technically robust and specific for the C7M neo-epitope. Serum C7M levels were significantly elevated in two cohorts of patients with SSc and in patients with COPD as compared with healthy individuals (P < 0.0001). The C7M ELISA enabled quantification of type VII collagen turnover in serum. Elevated serum C7M levels indicated that the turnover rate of type VII collagen was significantly increased in patients with SSc or COPD, suggesting a pathological role. Thus, the C7M ELISA may become useful in future investigations of type VII collagen turnover in fibroproliferative disorders, and it may prove a valuable tool for evaluating novel anti-fibrotic drugs.

Original languageEnglish
JournalASSAY and Drug Development Technologies
Volume16
Issue number2
Pages (from-to)123-131
ISSN1540-658X
DOIs
Publication statusPublished - 2018

Keywords

  • biomarkers
  • COPD
  • ELISA
  • extracellular matrix
  • systemic sclerosis
  • type VII collagen

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