High circulating elafin levels are associated with Crohn’s disease-associated intestinal strictures

Abstract

ObjectiveNearly 33% of Crohns disease (CD) patients develop intestinal strictures. Antimicrobial peptide or protein expression is associated with disease activity in inflammatory bowel disease (IBD) patients. Circulating blood cells and intestine of IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. However, the association between elafin and CD-associated intestinal stricture is unknown. We hypothesize the elafin expression in stricturing CD patients is abnormal. We determined the expression of elafin in blood, intestine, and mesenteric fat in IBD patients.\n\nMethodsHuman colonic and mesenteric fat tissues and serum samples were collected from the Cedars-Sinai Medical Center and UCLA, respectively.\n\nResultsHigh serum elafin levels were associated with a significantly elevated risk of intestinal stricture in CD patients. Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlation with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels, but the increase was not associated with endoscopic Mayo score. Colonic elafin mRNA and protein expression were not associated with clinical disease activity in IBD patients, while stricturing CD patients had low colonic elafin expression. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA expression, which may contribute to high circulating elafin level.\n\nConclusionHigh serum elafin levels and adipose elafin expression are associated with intestinal strictures, which may help identify intestinal strictures in CD patients.