Background Adult-onset Still's disease (AOSD) is a chronic inflammatory disease with unknown etiology, and complex networks incorporating many cytokines and chemokines are involved in its pathogenesis. The IL-33, soluble ST2 (sST2) and its pathway have important functions in immune regulation, host defense, and inflammation. Although serum sST2 level was demonstrated previously to be higher in sJIA, as well as other rheumatic diseases compared with healthy controls, there is a lack of information on its role in patients with AOSD.
Objectives The aims of this study were to evaluate whether serum levels of IL-33, sST2, and IL-33/sST2 ratio correlate with AOSD disease activity.
Methods Fifty-two patients who met Yamaguchi's criteria for AOSD were evaluated. The 52 patients with AOSD were assigned to active (n=23) or inactive (n=29) disease groups and were evaluated longitudinally a second time providing a total of 104 sets of serum samples. Serum samples were compared with 26 age- and sex-matched healthy controls (HC). Serum levels of IL-33 and sST2 were measured by enzyme-linked immunosorbent assay. Activity of AOSD was evaluated with mPouchot's score. Serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin were clinically used as indicators of disease activity.
Results Patients with active AOSD [338.9 (207.5–1107.1) pg/mL] had significantly higher serum sST2 concentrations than those with inactive AOSD [196.6 (58.7–437.8) pg/mL, p=0.01] and than HC [46.6 (10.1–119.2) pg/mL, p=0.002]. Serum sST2 levels changed according to the trend in the mPouchot's disease activity score (p=0.03, r =0.44), and positively correlated with clinical parameters of disease activity. Serum levels of IL-33 were not different between active AOSD, inactive AOSD, and HC. The IL-33/sST2 ratio decreased significantly in patients with AOSD [0.1 (0.04–0.29)] compared to that in HC [1.01 (0.21–3.89), p<0.001]. Even patients with inactive AOSD showed a lower IL-33/sST2 ratio than that of HC. The sST2 levels decreased significantly after treatment in the 23 patients with initially active AOSD [338.9 (207.5–1107.1) to 155.5 (43.7–260.6) pg/mL, p<0.001] and the IL-33/sST2 ratio increased significantly [0.07 (0.02-0.27) to 0.39 (0.06 – 0.93), p=0.005]. The cutoff points to distinguish patients and activity of AOSD from HC were determined by receiver operator characteristic curves. A cutoff value of 0.35 for the IL-33/sST2 ratio showed reliable sensitivity (80.0%) and specificity (72.2%) for differentiating patients with AOSD from HC. Sensitivity and specificity were 70.6% and 72.4%, respectively, when using levels of 232.9 pg/mL for serum sST2 as an active AOSD cutoff point.
Conclusions The IL-33/sST2 ratio decreased significantly in patients with AOSD compared with that in healthy controls. Serum sST2 level increased significantly in patients with AOSD compared to that in controls, and sST2 levels were much higher in patients with active AOSD than in patients with inactive AOSD. Serum sST2 levels correlated positively with the parameters of disease activity. These findings suggest that the IL-33/sST2 ratio is useful for differentiating AOSD and healthy controls and that sST2 level may be a promising surrogate marker of disease activity in patients with AOSD.
Disclosure of Interest : None declared