The clinical relevance of this proposed screen is that it would lead to the elusive and accurate diagnosis to circumvent the inexact IC patients into authentic CC and UC with a first clinic endoscopy biopsy. The central medical challenge in endoscopic medicine and colorectal surgery is the discrimination of colonic IBD into the subtypes with high accuracy because it greatly affects surgical care of patients. Incorrect diagnosis and surgery carry potential morbidity from inappropriate and unnecessary surgery and cost. Our published data has shown robust evidence supporting presence of human alpha-defensin 5 (DEFA5) in areas of the colon mucosa with aberrant expression of apparent Paneth cell-like cells (PCLCs) / crypt cell-like cells (CCLCs), which identifies an area of colonic ileal metaplasia, consistent with the diagnosis of CC. Investigators propose to demonstrate that UC and CC, the two unsolved medical subtypes of GI pathology with no drugs for a cure, may accurately be distinguished molecularly by examining CCLCs-secreted DEFA5 in colonic endoscopy biopsies instantly. Our proposal is highly innovative, as it highlights the robustness efficacy and safety of DEFA5 and its clinical relevance in IBD diagnostics. The goal of this proposal is to develop a clinical approach to circumvent diagnostic ambiguity and delay, as well as permit timely, and accurate diagnosis of colonic IBD. DEFA5 immunoreactivity in colonic endoscopy biopsies could be a potential diagnostic signature that accurately diagnoses CC and provides the basis to resolve ambiguity in the diagnosis of IBD to not only circumvent diagnostic delay, but also permit timely, accurate diagnosis and timely prescription of appropriate treatment options, an Affordable, Sensitive, Specific, User-friendly, Robust and Rapid, Equipment-free, and Deliverable (ASSURED) bioassay that may delineate subtypes of IBD during the first clinic endoscopy biopsy visit. This bioassay is specific, sensitive, linear, affordable, low risk, and less invasive. Investigators hypothesize that aberrant expression of DEFA5 secreting CCLCs in colonic crypt of IBD patients may be exploited as a reliable diagnostic signature to highly differentiate CC from UC in otherwise IC patients during the first clinic visit endoscopy biopsy without delay. Investigators foresee no issues pertaining to this proposal as an established sampling error by endoscopic biopsy making it does not interfere with results and apropos of this project that each biopsy has complement CCLCs with co-localized DEFA5 clearly restricted in areas of the mucosa with aberrant CCLCs identifies a ubiquitously colonic ileal metaplasia that is consistent with the diagnosis of authentic CC. If successful, widespread use of this approach would not only revolutionize provide accurate diagnoses and the correct treatment regimens for IBD patients, but also it will improve health outcomes and patient quality of life, while reducing medical complications and/or unnecessary drugs, surgeries, \& costs.
