Serum Proteomic Markers in Patients with Systemic Sclerosis in Relation to Silica Exposure

<b>Background:</b> Systemic sclerosis (SSc) is a multisystem autoimmune disease characterised by fibrosis, vasculopathy, and immune dysfunction. Silica exposure has been associated with a more aggressive phenotype of the disease, including diffuse cutaneous involvement and interstitial lung disease. This study aims to identify proteomic differences between SSc patients exposed to silica and those not exposed to silica. <b>Methods:</b> An observational study of 32 SSc patients (11 silica-exposed and 21 non-exposed) was performed, with occupational history and quantitative proteomic analysis using SWATH-MS mass spectrometry. Differentially expressed proteins were analysed, and functional pathway enrichment was performed. <b>Results:</b> Eight proteins showed significant differences between groups, all with reduced levels in silica-exposed patients: adiponectin, immunoglobulins (IGLV3-19, IGLV2-18), complement C2, alpha-2-macroglobulin, vitronectin, cytoplasmic actin 2, and pigment epithelium-derived factor. Alterations in pathways related to fibrinolysis, complement activation, and inflammation were highlighted, suggesting that silica exposure may influence the pathogenesis of SSc and worsen its clinical course. <b>Conclusions:</b> This study supports the hypothesis that silica exposure is not only a triggering factor for SSc, but is also modulating its progression through inflammatory, procoagulant, and fibrotic pathways. The identification of proteomic biomarkers could contribute to the phenotypic classification of patients and the development of personalised therapies. Future studies should expand the cohort and further investigate the functional mechanisms of these proteins in SSc.