A 23-Plex Cytokine/Chemokine Analysis Identifies TNFRII, MMP-8, and sIL-1RII as Potential Biomarkers for Systemic Sclerosis

<b>Background:</b> Reliable biomarkers are urgently needed to aid in the differential diagnosis, prognosis, disease progression monitoring, and prediction of therapeutic response in patients with systemic sclerosis (SSc). This study aimed to evaluate a panel of potentially pathogenic circulating cytokines and chemokines in a cohort of SSc patients. <b>Methods:</b> Serum samples were obtained from 35 SSc patients and 40 age- and sex-matched healthy controls. Twenty-three cytokines/chemokines were quantified using a Luminex^® multiplex immunoassay (BioRad-BioPlex 200 System-Lumine x-Map technology R&D Systems, USA) following the manufacturer's instructions and customized procedures. Data were acquired using Bioplex manager v 6.1. Data analysis was performed using GraphPad Prism v.8 (GraphPad Software, Inc.), with significance defined as <i>p</i> ≤ 0.05. V.8 <b>Results:</b> Levels of TNFRII and MMP-8 were significantly higher in SSc patients compared to healthy controls, while IL-1RII levels were significantly elevated in healthy individuals (<i>p</i> < 0.001 for all comparisons). Patients with elevated ESR at baseline (>30 mm/h) showed higher IL-15 levels (<i>p</i> = 0.019). A strong positive correlation was found between MCP-1 and the modified Rodnan skin score (mRSS) (<i>p</i> = 0.009, r = 0.740), and a moderate correlation between TNFRII and diffusing capacity for carbon monoxide (<i>p</i> = 0.046, r = 0.339). PLS regression identified MMP-8, MCP-1, TNFRII, IL-15, and IL-1RII as key predictors of SSc, with MMP-8 having the strongest influence. The logistic regression model showed high performance (AUC = 0.93, accuracy = 87.5%). <b>Conclusions:</b> TNFRII, MMP-8, and IL-1RII may play a pathogenic role in SSc. TNFRII, in particular, may serve as a biomarker for pulmonary involvement, aligning with its known role in pro-fibrotic pathways. These findings support their utility in diagnosis and disease profiling.