Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2011; 17(17): 2181-2190
Published online May 7, 2011. doi: 10.3748/wjg.v17.i17.2181
Soluble ST2: A new and promising activity marker in ulcerative colitis
David Díaz-Jiménez, Lucía E Núñez, Caroll J Beltrán, Enzo Candia, Cristóbal Suazo, Manuel Álvarez-Lobos, María-Julieta González, Marcela A Hermoso, Rodrigo Quera
David Díaz-Jiménez, Lucía E Núñez, Caroll J Beltrán, Enzo Candia, Marcela A Hermoso, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, CL 8380453, Chile
Caroll J Beltrán, Department of Clinical Investigation, Hospital Clínico de la Universidad de Chile, Santiago, CL 8380456, Chile
Cristóbal Suazo, Laboratory of Oncology and Molecular Genetics, Colorectal Surgery Unit, Clínica Las Condes, Lo Fontecilla 441, Santiago, CL 7591046, Chile
Manuel Álvarez-Lobos, Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, CL 8380074, Chile
María-Julieta González, Cell and Molecular Biology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, CL 8380453, Chile
Rodrigo Quera, Gastroenterology Unit, Department of Internal Medicine, Hospital Clínico de la Universidad de Chile, Santiago, CL 8380456, Chile
Rodrigo Quera, Gastroenterology Unit, Clínica Las Condes, Lo Fontecilla 441, Santiago, CL 7591046, Chile
Author contributions: Díaz-Jiménez D and Núñez LE performed the majority of experiments; Beltrán CJ and Candia E were also involved in performing some experiments and collected patient information; Hermoso MA and González MJ provided vital reagents and analytical tools and edited the manuscript; Quera R co-ordinated and provided the collection of all the human material in addition to providing financial support for this work; Suazo C and Álvarez-Lobos M also provided human samples; Hermoso MA designed the study; Hermoso MA and Díaz-Jiménez D wrote the manuscript; Hermoso MA and Quera R share senior authorship.
Supported by FONDECYT grant 1070954 and DA-CLC 2803
Correspondence to: Rodrigo Quera, MD, Gastroenterology Unit, Clínica Las Condes, Lo Fontecilla 441, Santiago, CL 7591046, Chile. rquera@clinicalascondes.cl
Telephone: +56-2-6108755 Fax: +56-2-6108719
Received: July 22, 2010
Revised: October 15, 2010
Accepted: October 22, 2010
Published online: May 7, 2011
Abstract

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 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).

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.

Keywords: Inflammatory bowel disease; Ulcerative colitis; Soluble ST2; Biomarkers