Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

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.

An engineering probiotic producing defensin-5 ameliorating dextran sodium sulfate-induced mice colitis via Inhibiting NF-kB pathway

“…A previous study demonstrated a deficiency of human α-defensin expression in subjects with IBD [29]; and defensins released by Paneth cells appear to be critical in the pathogenesis and progression of IBD [30,31]. Besides, human α-Defensin-5 could be used as a potential candidate biomarker to molecularly differentiate Crohn's colitis (high levels of Human α-Defensin-5) from UC (low levels of Human α-Defensin-5) [32]. In this study, we used the typical DSS mouse model of colitis to test the effects of α-defensin administration in the pathophysiology of colitis.…”

Prognostic effect of inflammatory genes on stage I-III colorectal cancer – integrative analysis of TCGA data

“…DEFA5 encodes a family of antimicrobial and cytotoxic peptides thought to be involved in host defense [29]. It is reported as a candidate biomarker for Crohn's disease [48]. PRG4 encodes a large proteoglycan [29].…”

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

“…Therefore, a total of 30% of colonic IBD patients are not diagnosed accurately [258][259][260]. For these reasons, efforts at identifying accurate, noninvasive biomarkers have been undertaken [263][264][265]. Another really challenge is a significant subgroup of IBD patients, especially UC patients undergoing proctocolectomy that convert to de novo Crohn's, are thought to be "misdiagnosed" [265].…”

“…For these reasons, efforts at identifying accurate, noninvasive biomarkers have been undertaken [263][264][265]. Another really challenge is a significant subgroup of IBD patients, especially UC patients undergoing proctocolectomy that convert to de novo Crohn's, are thought to be "misdiagnosed" [265]. This may not be accurate because there is a possibility that these patients with UC were "transformed" due to an altered microbiome ecology in the pouch and immune environment and that the patient actually "convert".…”

“…A recent breakthrough finding that Paneth cell specific peptide "Human alpha-defensin 5 (DEFA5)" delineate colonic IBD (CC versus UC) may solve diagnostic dilemma in IBD clinical settings [265]. Detection of DEFA5 more accurately circumvented the IC cases into UC or CC phenotype and identified CC cases initially treated as UC cases [265]. Among patients with IC, DEFA5 is a reliable delineator with a positive predictive value of 96 percent [265].…”