4.7 Article

Bronchoalveolar lavage proteomic analysis in pulmonary fibrosis associated with systemic sclerosis: S100A6 and 14-3-3ε as potential biomarkers

Journal

RHEUMATOLOGY
Volume 58, Issue 1, Pages 165-178

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/key223

Keywords

pulmonary fibrosis; systemic sclerosis; protein species; proteomics; enrichment analysis; 14-3-3 epsilon; S100A6; C3a; surfactant-associated protein A2; APOAI

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Objective. SSc is a rare severe connective tissue disorder. Its prognosis is mainly related to the development of pulmonary fibrosis (PF)-SSc and pulmonary arterial hypertension. No known therapy for PF-SSc modifies progressive lung fibrotic involvement. Research is therefore aimed at a deeper understanding of complex pathogenetic mechanisms and the possibility of new prognostic biomarkers and therapeutic targets. Methods. Towards the first of these aims, we conducted functional proteomic analysis of bronchoalveolar lavage samples from PF-SSc patients and smoker and non-smoker controls. Results. The differential expression pattern revealed by principal component analysis highlighted a specific protein profile of PF-SSc with respect to control samples, and enrichment analysis shed light on process networks involved in pathogenesis. The proteins identified are known to be involved in lung inflammation of PF-SSc-induced IL6 signalling, the complement system, innate immunity, Jak-STAT, the kallikrein-kinin system, blood coagulation, the immune response mediated by phagocytosis and phagosomes in antigen presentation. In particular, our MetaCore network suggested C3a, APOAI, 14-3-3 epsilon, SPFA2 and S100A6 as potential biomarkers; these are upstream molecules involved in lung fibrosis, innate immunity and vascular damage occurring in PF-SSc. Conclusion. This report provides a molecular overview of pathological processes in PF-SSc, pinpointing possible new disease biomarkers and therapeutic targets.

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