Bronchoalveolar lavage proteomic analysis in pulmonary fibrosis associated with systemic sclerosis: S100A6 and 14-3-3ε as potential biomarkers. (17th September 2018)

• Record Type: Journal Article
• Authors: Landi, Claudia; Bargagli, Elena; Carleo, Alfonso; Refini, Rosa Metella; Bennett, David; Bianchi, Laura; Cillis, Giuseppe; Prasse, Antje; Bini, Luca; Rottoli, Paola
• Is Part Of: Rheumatology. Volume 58(2019)Supplement 1
• Page Start: 165
• Page End: 178
• Publication Date: 2018-09-17
• Subjects: pulmonary fibrosis -- systemic sclerosis -- protein species -- proteomics -- enrichment analysis -- 14-3-3ε -- S100A6 -- C3a -- surfactant-associated protein A2 -- APOAI; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/key223
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: 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, 14-3-3ε, 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.