Serum Dipeptidyl Peptidase 4: A Predictor of Disease Activity and Prognosis in Inflammatory Bowel Disease

Abstract

Abstract Background Serum dipeptidyl peptidase 4 (DPP-4) has drawn particular interest as a biomarker in inflammatory bowel disease (IBD), as this protease inactivates several peptides that participate in the inflammatory cascade. Methods Two prospectively recruited cohorts consisting of 195 patients (101 had Crohn’s disease [CD] and 94 had ulcerative colitis [UC]) were evaluated using clinical indexes and followed up to assess for treatment escalation. Sixty-eight patients underwent endoscopic evaluation at baseline. In the second cohort of 46 biologically treated patients, treatment response was assessed. Serum DPP-4, C-reactive protein (CRP), and fecal calprotectin levels were quantified at baseline and during follow-up. Results Median DPP-4 levels were significantly lower in active IBD patients when compared with remitters (CD: 1043 [831–1412] vs 1589 [1255–1956] ng/mL; P < 0.001; UC: 1317 [1058–1718] vs 1798 [1329–2305] ng/mL; P = 0.001) and healthy controls (2175 [1875–3371] ng/mL). In fact, DPP-4 was able to distinguish clinical and endoscopic activity from remission, with areas under the curve (AUC) of 0.81/0.93 (CD) and 0.71/0.79 (UC), along with the need for treatment escalation, with comparable AUCs of 0.79 (CD) and 0.77 (UC). Furthermore, DPP-4 levels were higher in responders to treatment and more pronounced among UC (1467 [1301–1641] vs 1211 [1011–1448] ng/mL; P < 0.001) than CD patients (1385 [1185–1592] vs 1134 [975–1469] ng/mL; P = 0.015). Conclusions Our results suggest that serum DPP-4 can be used as a noninvasive biomarker of IBD activity and biological treatment response and a predictor of treatment escalation, particularly when combined with other biomarkers.