title: Soluble ST2: a new and promising activity marker in ulcerative colitis.
abstract: OBJECTIVE
  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 histopathological 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, CL 8380453, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Díaz-Jiménez
authors.forename: Lucía E
authors.initials: LE
authors.lastname: Núñez
authors.forename: Caroll J
authors.initials: CJ
authors.lastname: Beltrán
authors.forename: Enzo
authors.initials: E
authors.lastname: Candia
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Suazo
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez-Lobos
authors.forename: María-Julieta
authors.initials: MJ
authors.lastname: González
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Hermoso
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Quera
mesh_terms: D000328:Adult; D015415:Biomarkers; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000097:blood*; D003106:Colon / Q000737:chemistry; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood* / Q000502:physiology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface