Soluble ST2:A new and promising activity marker in ulcerative colitis

AIM:To correlate circulating soluble ST2(sST2) levels with the severity of ulcerative colitis(UC) and serum levels of pro-inflammatory cytokines,and to demonstrate the predictive power of sST2 levels for differentiation between active and inactive UC.METHODS:We recruited 153 patients:82 with UC,26 with Crohn's disease(CD) and 43 disease controls [non-inflammatory bowel disease(IBD)].Subjects were excluded if they had diagnosis of asthma,autoimmune diseases or hypertension.The serum levels of sST2 and pro-inflammatory cytokines [pg/mL;median(25th-75th)] as well as clinical features,endoscopic and histological features,were subjected to analyses.The sST2 performance for discrimination between active and inactive UC,non-IBD and healthy controls(HC) was determined with regard to sensitivity and specificity,and Spearman's rank correlation coefficient(r).To validate the method,the area under the curve(AUC) of receiver-operator characteristic(ROC) was determined(AUC,95% CI) and the total ST2 content of the colonic mucosa in UC patients was correlated with circulating levels of sST2.RESULTS:The serum sST2 value was significantly higher in patients with active [235.80(90.65-367.90) pg/mL] rather than inactive UC [33.19(20.04-65.32) pg/mL],based on clinical,endoscopic and histopathological characteristics,as well as compared with non-IBD and HC(P < 0.001).The median level of sST2 in CD patients was 54.17(35.02-122.0) pg/mL,significantly higher than that of the HC group only(P < 0.01).The cutoff was set at 74.87 pg/mL to compare active with inactive UC in a multicenter cohort of patients.Values of sensitivity,specificity,and ability to correctly classify UC,according to activity,were 83.33%,83.33% and 83.33%,respectively.The AUC of the ROC curve to assess the ability of this molecule to discriminate between active vs inactive UC was 0.92(0.86-0.97,P < 0.0001).The serum levels of sST2 in patients with UC significantly correlated with endoscopic and histo-pathological scores(r = 0.76 and r = 0.67,P < 0.0001,respectively),and with the pro-inflammatory cytokine,tumor necrosis factor-α(r = 0.69 and r = 0.61,respectively,P < 0.0001).Interestingly,we found a direct correlation between total intestinal ST2 content and serum levels of sST2,adjusted to endoscopic activity score in patients with mild(r = 0.44,P = 0.004),moderate(r = 0.59,P = 0.002) and severe disease(r = 0.82,P = 0.002).Only patients with inactive UC showed no significant correlation(r = 0.45,P = 0.267).CONCLUSION:sST2 levels correlated with disease severity and inflammatory cytokines,are able to differentiate active from inactive UC and might have a role as a biomarker.