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AB0192 Discovery of potential skin biopsy biomarkers for systemic sclerosis by high-throughput proteomic approaches

Background Systemic Sclerosis (SSc) is an autoimmune connective tissue rheumatic disease characterised by three main hallmarks; vasculopathy, immune system abnormalities and fibrosis. It is considered a multisystemic and heterogeneous disease as many organs of the body may be affected and symptoms vary among patients. Up to date, SSc is untreated and its etiology and pathogenesis remain unclear. Early prognosis and diagnosis of the disease are challenging. Objectives The aim of this study was to analyse the proteomic profile of SSc patients in order to gain insights into the mechanisms implicated in disease pathogenesis and also discover new biomarkers that would facilitate early prognosis, more accurate diagnosis and therapeutic targeting of SSc. Methods Human biopsies were obtained from ten affected and three non-affected skin areas of SSc patients and have been classified based on histological criteria. Biopsies were cryo-pulverised and proteins were extracted, purified, reduced, alkylated and digested by trypsin. Purified peptides were analysed on a Waters Synapt G2Si HDMS instrument operated in ion mobility mode using a UDMSE approach. Data were processed by the Progenesis QIp and functional annotation analysis was carried out using multiple bioinformatics resources. Results Proteomic analysis led to the identification and quantification of approximately 1500 non-redundant proteins per sample. About 400 of these proteins, including interferons and interleukins, are differentially expressed between affected and non-affected samples. Functional annotation analysis of these proteins showed that they are involved in multiple pathways including, antigen processing and presentation, complement, ubiquitin mediated proteolysis and Notch signalling, which are known to be associated with autoimmune diseases and fibrosis. Conclusions Using a Mass Spectrometry-based proteomic approach for the analysis of SSc human skin biopsies, we identified a number of proteins that might be involved in the development and pathogenesis of SSc. Interestingly, some of these proteins are differentially expressed in specific histological groups and thus could be considered as potential biomarkers for specific SSc stages. Acknowledgements This work has received support from the EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n° 115565, the Cyprus Institute of Neurology and Genetics and Université catholique de Louvain. Disclosure of Interest None declared