Serum Isthmin-1 and Irisin profiles and their association with clinical parameters in fibromyalgia: a cross-sectional...

Fibromyalgia Syndrome (FM) is a chronic pain disorder characterized by a complex pathophysiology that lacks definitive biochemical markers. This study aims to evaluate the serum levels of Isthmin-1 (ISM1) and Irisin in patients with FM and to investigate their relationship with clinical parameters such as pain severity and depressive symptoms. This cross-sectional study included 21 female patients diagnosed with FM according to the ACR 2016 criteria and 21 age- and BMI-matched healthy female controls. Pain intensity was assessed using the Visual Analog Scale (VAS), and psychological status was evaluated with the Beck Depression Inventory (BDI). Serum ISM1 and Irisin levels were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Statistical analyses were performed using non-parametric tests, and correlations were evaluated via Spearman's rank correlation coefficient. The FM and control groups were well-matched regarding age [46 (33-59) vs. 47 (35-59) years; p = 0.489] and BMI [27.0 (20.8-34.7) vs. 26.4 (21.3-33.8) kg/m²; p = 0.670]. As expected, VAS [7 (6-8) vs. 1 (0-3); p < 0.001] and BDI [34 (26-40) vs. 5 (0-9); p < 0.001] scores were significantly higher in the FM group. Serum ISM1 levels were significantly lower in the FM group compared to the control group [3152.40 (2693.54-3511.76) pg/mL vs. 4083.29 (2659.13-5962.67) pg/mL, respectively; p < 0.001], whereas no significant difference was observed in serum Irisin levels between the groups [423.34 (285.73-554.24) ng/mL vs. 396.95 (274.53-612.71) ng/mL, respectively; p = 0.580]. Correlation analysis within the FM group showed strong negative correlations between serum ISM1 levels and BDI scores (rho = -0.721, p = 0.001), as well as between ISM1 and VAS scores (rho = -0.710, p = 0.001). Additionally, a significant negative correlation was found between serum ISM1 and Irisin levels strictly within the patient cohort (rho = -0.458, p = 0.037). Our findings demonstrate for the first time that serum ISM1 levels are markedly reduced in patients with FM and are strongly associated with both pain and depression. While Irisin levels remained stable, the significant decrease in ISM1 suggests that it may serve as a potential objective biomarker for the diagnosis and clinical monitoring of FM.