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Introduction: Autoimmune-mediated connective tissue diseases (AIMCTD) and systemic vasculitides are heterogeneous inflammatory disorders characterized by immune dysregulation, autoantibody production, and multi-organ involvement. Reliable biomarkers for disease activity, organ involvement, and cardiovascular risk remain limited. Soluble suppression of tumorigenicity-2 (sST-2), a circulating form of the interleukin-33 receptor, has recently emerged as a potential cardiovascular and inflammatory biomarker, while Nostrin, an endothelial nitric oxide synthase regulator, may reflect endothelial dysfunction. This study aimed to evaluate the diagnostic and prognostic potential of sST-2 and Nostrin across multiple autoimmune rheumatic diseases.

Methods: This retrospective observational cohort study included 131 patients with autoimmune inflammatory diseases (ANCA-associated vasculitis, idiopathic inflammatory myopathies, polymyalgia rheumatica, sarcoidosis, systemic sclerosis, systemic lupus erythematosus, and Sjögren’s disease) and 42 healthy controls. Serum concentrations of sST-2 and Nostrin were measured using sandwich ELISA. Clinical data included inflammatory markers, cardiovascular risk factors, renal parameters, lifestyle variables, glucocorticoid exposure, and disease-specific activity indices. Statistical analyses assessed correlations between biomarker levels and clinical variables across disease groups.

Results: In the overall cohort, sST-2 showed significant positive correlations with inflammatory markers (CRP, ESR), age, urinary albumin/creatinine ratio, and glucocorticoid dose. Additional associations were observed with sex, obesity, hypertension, and smoking status. Disease-specific analyses revealed particularly strong correlations in Sjögren’s disease and polymyalgia rheumatica, including relationships with disease activity scores, renal markers, and cardiovascular risk parameters. In idiopathic inflammatory myopathy, sST-2 correlated with the Framingham cardiovascular risk score. Nostrin demonstrated only limited associations, primarily with CRP and glucocorticoid dose in the overall cohort, and showed minimal disease-specific correlations.

Conclusion: sST-2 appears to be a broadly responsive biomarker reflecting systemic inflammation, renal involvement, and cardiovascular risk factors across autoimmune rheumatic diseases, although it lacks disease specificity. Nostrin showed limited diagnostic value in this heterogeneous population. Future studies should focus on longitudinal analyses and disease-specific validation to clarify the clinical utility of sST-2 in autoimmune diseases.