Sensitive Clinical Marker Defined for Ulcerative Colitis Evolution

The two main subtypes of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by episodes of inflammatory activity and remission and determination of disease activity remains challenging, with most clinical scores correlating poorly with the inflammatory state.

Treatment of IBD patients has recently shifted from controlling symptoms to promoting endoscopic mucosal healing or deep remission and treatment promoting mucosal healing can slow the progression of the disease. In this context, laboratory biomarkers have gained importance in evaluating and predicting the response to therapy.

Scientists at the University of Chile (Santiago, Chile) prospectively recruited 26 patients grouped according to an endoscopic score and therapy response. Colonoscopic biopsies were collected at baseline and six months or when patients showed clinical activity. The protocol was reinitiated in patients requiring rescue therapy. Blood and stool were collected at baseline, one, three, six and 12 months.

Serum and intestinal ST2 (Interleukin 1 receptor-like 1) concentrations, as well as serum interleukin -33 (IL-33) levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit for human ST2 or IL-33 (DuoSet, R&D Systems, Minneapolis, MN, USA). The ST2 detection assay is stable over time, with a detection limit of 20 pg/mL, while the IL-33 detection assay is less stable over time, with a detection limit of 23.4 pg/mL. The supernatant from the fecal samples were processed for the rapid semi-quantitative test Calprotectin 50+200 (CerTest Biotec S.L., Zaragoza, Spain). Mucosal ST2 detection was performed by immunofluorescence and the images captured using an Olympus confocal laser scanning biological microscope FV10i (Olympus America Inc., Melville, NY, USA).

The team reported that follow-up was completed in 24 patients. The statistically significant median and range of soluble sST2 levels varied from 173.5 pg/mL (136.6–274.0) to 86.5 pg/mL (54.6–133.2) in responders and 336.3 pg/mL (211.0–403.2) to 385.3 pg/mL (283.4–517.3) in non-responders at baseline and six months respectively. Soluble sST2 levels correlated with Mayo clinical and endoscopic subscore, mucosal ST2 and fecal calprotectin (FC) and showed a trend similar to that of FC in responders. Non-responders revealed an increased ST2 content, restricted to the lamina propria’s cellular infiltrate.

The authors concluded that during the follow-up, serial ST2 measurements decreased in those patients with a reduced endoscopic index at six months, indicating a positive response to therapy. In those patients, FC levels were also significantly decreased in direct correlation to sST2 levels. The accuracy of sST2 in endoscopic detection of UC strongly suggests its usefulness in monitoring relapse and outcome, as well as in identifying patients likely to benefit from a particular treatment. The study was published on August 28, 2016, in the journal BMC Gastroenterology.

Related Links:
University of Chile
R&D Systems
CerTest Biotec
Olympus America