Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders
| Autor: | Juan C. Chavez, Jannie M.B. Sand, Patricia Lamy, Martin R. Larsen, Diana Julie Leeming, Pernille Juhl, Anne Sofie Siebuhr, Line V. Iversen, Arkadiusz Nawrocki, Robyn T. Domsic, Nathalie Franchimont, Morten A. Karsdal |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Collagen Type VII medicine.drug_class systemic sclerosis extracellular matrix Enzyme-Linked Immunosorbent Assay Monoclonal antibody Serology Extracellular matrix Cohort Studies 03 medical and health sciences Epitopes Pulmonary Disease Chronic Obstructive 0302 clinical medicine type VII collagen Interstitial matrix Drug Discovery Anchoring fibrils Medicine Humans COPD Pathological Aged Basement membrane Scleroderma Systemic business.industry biomarkers Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Molecular Medicine Female ELISA business |
| Zdroj: | Sand, J M B, Lamy, P, Juhl, P, Siebuhr, A S, Iversen, L V, Nawrocki, A, Larsen, M R, Domsic, R T, Franchimont, N, Chavez, J, Karsdal, M A & Leeming, D J 2018, ' Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders ', ASSAY and Drug Development Technologies, vol. 16, no. 2, pp. 123-131 . https://doi.org/10.1089/adt.2017.820 |
| DOI: | 10.1089/adt.2017.820 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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