Reduced serum Irisin levels in systemic sclerosis: a cross-sectional case-control study

Irisin is a muscle-derived myokine implicated in metabolic regulation, endothelial function, inflammation, and fibrotic remodeling. Its relevance in systemic sclerosis (SSc), a disease characterized by autoimmunity, vasculopathy, and fibrosis, remains unknown. To compare serum Irisin levels between patients with SSc and healthy controls and to evaluate their associations with clinical-serological phenotype and organ-domain involvement in SSc.

This single-center cross-sectional case-control study included 52 patients with SSc and 47 healthy controls. Serum Irisin was measured by ELISA. Clinical-serological subsets, nailfold videocapillaroscopy findings, modified Rodnan skin score, pulmonary function, HRCT-derived ILD and Warrick scores, echocardiographic variables, gastrointestinal involvement, comorbidities, treatment exposure, and laboratory parameters were assessed. Adjusted analyses used log-linear models with robust standard errors.

Serum Irisin levels were significantly lower in SSc patients than in controls [696.70 pg/mL, IQR 611.16-1288.50 vs. 755.84 pg/mL, IQR 689.34-1899.75; p = 0.004]. This association remained significant after adjustment for age, sex, BMI, and smoking status, corresponding to 23.8% lower Irisin levels in SSc. Exploratory within-SSc analyses suggested lower Irisin levels in diffuse SSc and Scl-70-positive disease, particularly in adjusted models; however, unadjusted subgroup comparisons were weaker and should be interpreted cautiously. Irisin was not associated with NVC damage burden, mRSS, ILD severity, pulmonary function, or echocardiographic variables.

Serum Irisin levels are reduced in patients with SSc compared with healthy controls. Exploratory phenotype analyses suggest a possible association with diffuse/Scl-70-related disease, but this signal requires confirmation in independent cohorts. Irisin did not reflect established organ-domain damage, suggesting that it may represent a broader myokine-metabolic alteration in SSc rather than a direct organ severity biomarker. Key Points • Serum Irisin levels were lower in patients with systemic sclerosis than in healthy controls. • Exploratory phenotype analyses suggested lower Irisin levels in diffuse and Scl-70-positive SSc, but these subgroup findings require cautious interpretation. • Serum Irisin was not associated with NVC damage, skin score, ILD severity, pulmonary function, or echocardiographic variables.