Objectives: With galectin-3 playing an important role in inflammatory responses, elevated galectin-3 levels have been shown in patients with autoimmune diseases. However, there are limited data regarding galectin-3 expression in patients with autoinflammatory diseases such as adult-onset Still's disease (AOSD). This study aimed to investigate the extracellular galectin-3 expression and examine its association with activity parameters and disease outcome in AOSD patients.
Method: Plasma levels of galectin-3 and inflammasome downstream cytokines including interleukin (IL)-1β and IL-18 were determined by ELISA in 42 active AOSD patients and 20 healthy controls (HC). The protein levels of galectin-3 and cytokines were determined using immunoblotting.
Results: Plasma levels of galectin-3 and inflammasome downstream cytokines including IL-1β and IL-18 were significantly higher in AOSD patients (median 5.02 ng/ml, interquartile range [IQR] 3.12-7.88 ng/ml; 3.42 pg/ml, IQR 1.48-6.70 pg/ml; and 5758 pg/ml, IQR 859-11,895 pg/ml, respectively) compared with HC (1.86 ng/ml, IQR 1.09-2.89 ng/ml; 0.99 pg/ml, IQR 0.62-1.35 pg/ml; and 129 pg/ml, IQR 71-155 pg/ml, respectively, all p < 0.001). Plasma galectin-3 levels were positively correlated with clinical activity scores, inflammatory parameters values, and the levels of IL-1β and IL-18 in AOSD patients. AOSD patients with systemic pattern had significantly higher galectin-3 levels (median 6.08 ng/ml, IQR 4.01-9.54 ng/ml) compared with those with chronic articular pattern (3.56 ng/ml, IQR 3.04-4.98 ng/ml, p < 0.05). After 6-month therapy, galectin-3 levels significantly declined, paralleling the decreases in clinical activity scores and plasma levels of IL-1β and IL-18.
Conclusions: Elevated galectin-3 levels and their positive correlation with disease activity scores, inflammatory parameter, and inflammasome downstream cytokines suggest the involvement of galectin-3 in AOSD pathogenesis.Key Points• We revealed for the first time the association of plasma galectin-3 levels with AOSD activity parameters.• We explored the link between galectin-3 levels and NLRP3-inflammasome downstream cytokines in AOSD disease.
Keywords: Adult-onset Still’s disease (AOSD); Disease outcome; Galectin-3; Inflammasome; Inflammatory parameters.