Serum Regenerating Islet-Derived 3-Alpha is a Biomarker of Celiac Disease and other Enteropathies

Background The clinical presentation of organic and functional intestinal disorderscan overlap and clinicians often rely on invasive and time-consuming procedures to make a final diagnosis. Regenerating islet-derived 3-alpha (Reg3a) is detectable in the circulation of patients with intestinal graft-versus host disease and patients with inflammatory bowel disease (IBD). Aim To determine whether serum Reg3a testing is useful for discriminating mucosal enteropathies from functional intestinal disorders. Methods We prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn’s disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and after 6–12 months of a gluten-free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut-off value. Reg3a levels were measured by a commercial ELISA kit. Results Levels of Reg3a exceeded the cut-off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn’s disease patients, 17/22(77%) UC patients and one patient with IBS (4%). Reg3a levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3a levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX. Conclusion Reg3a is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies. Aliment Pharmacol Ther