Abstract
Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.
Highlights
Managing phenotypic outcomes of indeterminate colitis (IC), given its unpredictable clinical presentation and disease course, is challenging in endoscopic medicine [1,2]
Change of diagnosis of IC to ulcerative colitis (UC) or Crohn’s colitis (CC) is sometimes observed in patients with inflammatory bowel disease (IBD) before colectomy, as is the development of de novo Crohn’s disease after surgery, restorative proctocolectomy (RPC) and ileal pouch-anal anastomosis (IPAA) [1,10,12,13,14]
Nearly 30% of indeterminate colitis patients cannot be delineated into UC or CC
Summary
Managing phenotypic outcomes of indeterminate colitis (IC), given its unpredictable clinical presentation and disease course, is challenging in endoscopic medicine [1,2]. Change of diagnosis of IC to UC or CC is sometimes observed in patients with IBD before colectomy, as is the development of de novo Crohn’s disease after surgery, restorative proctocolectomy (RPC) and ileal pouch-anal anastomosis (IPAA) [1,10,12,13,14]. This paper describes a potential diagnostic molecular biomarker for reclassifying IC into an accurate clinical diagnosis of UC or CC prior to appropriate care intervention. These successful studies are the first of their kind to use tissue molecular biometrics in the colon microenvironment to delineate the colitides [6,7]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have