Soluble syndecan-1 as marker of intestinal inflammation: A preliminary study and evaluation of a new panel of biomarkers for non-invasive prediction of active ulcerative colitis.

Abstract

Syndecan-1 (Sdc1) is a heparin sulfate proteoglycan expressed in intestinal epithelium, which plays a crucial role in inflammation and epithelial repair. Sdc1-knockout mice have a deteriorated course of dextran sulfate sodium-induced colitis as compared to controls. Syndecan-1 is also shed into the serum during inflammation of the epithelium. We hypothesized that an increased serum level of soluble Sdc1 is a biomarker of intestinal inflammation in ulcerative colitis (UC). To evaluate serum soluble Sdc1 as a biomarker of intestinal inflammation in UC. This is a proof-of-concept study. Patients were recruited by the University Hospital Münster and HELIOS Albert Schweitzer Klinik Northeim (Germany). Blood samples were collected from UC patients actively suffering from this condition and those in remission. The levels of Sdc1 were measured with Diaclone CD 138 ELISA kit (Diaclone Research, Besançon, France) and routine clinical data were collected (C-reactive protein (CRP) levels, calprotectin in stool samples). Data were analyzed using SPSS software. Soluble Sdc1 levels were significantly elevated in the active UC group as compared to the inactive UC group (94.5 ±68.1 ng/mL compared to 28.3 ±12.6 ng/mL, p = 0.0020). The levels of Sdc1 also significantly correlated with the severity of UC as measured with the Mayo score (p = 0.0248). Receiver operating characteristic (ROC) analysis showed a good correlation of Sdc1 with an endoscopic Mayo score ≥2, with a value of 0.7747 (95% confidence interval (95% CI) = 0.5775-0.9718). A cutoff value of 37.1 ng/mL of Sdc1 showed a sensitivity of 78% and a specificity of 77%. A panel of biomarkers including CRP, hemoglobin, hematocrit, and Sdc1 was able to precisely predict active UC with an area under the curve (AUC) = 0.9395 (95% CI = 0.8509-1.0000). Serum soluble Sdc1 correlates significantly with mucosa inflammation and Mayo score in UC. Clinical trials No. NCT02333526.