Abstract
<title>Abstract</title> <p>Background Systemic sclerosis is a heterogeneous autoimmune disease associated with decreased life quality and expectancy. As fully curative treatment is not available, early and accurate risk stratification remains an unmet need. Lipids are involved in vascular and immune regulation – two key processes of systemic sclerosis pathogenesis. Therefore, this study aimed to characterise fatty acid profiles in systemic sclerosis and to assess their potential diagnostic and clinical relevance. Methods The study included 54 systemic sclerosis patients, 36 rheumatoid arthritis patients, and 43 healthy adults. Rheumatoid arthritis was included as an additional control group with autoimmune disease to help distinguish systemic sclerosis-specific fatty acid alterations from changes related more broadly to autoimmunity, inflammation, comorbidities, and long-term pharmacotherapy. Their clinical data and serum samples were collected. Fatty acid measurement was performed using gas chromatography-mass spectrometry. Differences between studied groups and subgroups of systemic sclerosis were assessed using appropriate univariate tests. Multivariate analyses included principal component analysis and partial least squares discriminant analysis. Diagnostic performance was evaluated using receiver operating characteristics. Results Patients with systemic sclerosis showed a global decrease in serum fatty acid concentrations compared with both rheumatoid arthritis patients and healthy controls. Several fatty acids and fatty acid classes demonstrated discriminatory potential, particularly in systemic sclerosis versus rheumatoid arthritis comparisons. The multivariate model discriminating systemic sclerosis from rheumatoid arthritis showed good classification performance, with an area under the curve of 0.87. Weaker discrimination was found for systemic sclerosis versus healthy control (area under the curve 0.68). Candidate biomarkers mainly included polyunsaturated and branched-chain fatty acids. Fatty acid alterations were more pronounced in active systemic sclerosis. Several potential biomarkers for disease activity were indicated, whereas no biomarkers of specific organ involvement were identified after correction for multiple testing. Conclusions Systemic sclerosis is characterised by a distinct fatty acid profile, different from healthy controls and rheumatoid arthritis. Our findings suggest that fatty acid profiling may provide candidate biomarkers for systemic sclerosis, particularly in relation to disease activity. Further studies on larger independent groups are needed to validate the presented observations and clarify the mechanisms underlying fatty acid disturbances in systemic sclerosis.</p>