Inflammatory Bowel Disease
Clinical Laboratory Tools to Aid Differentiation of Crohn’s Disease from Ulcerative Colitis
Lisa M Davis, PhD,1 Cole Harris, MS,2 Allison Treloar, MS3 and John Alsobrook II, PhD4
1. Senior Vice President, Product Development; 2. Senior Vice President, Discovery; 3. Director, Laboratory Operations; 4. Chief Scientific Officer, Exagen Diagnositcs
Abstract
Few laboratory tests are available for the differential diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD), the two major forms of inflammatory bowel disease (IBD). Tests measuring serum antibodies, acute phase proteins, and fecal proteins are useful in IBD diagnosis, but have limited utility as differential diagnostics, leaving endoscopy and histopathology as the gold standards. The next generation laboratory blood test for differentiating UC and CD is reviewed here. This test was developed from computational analysis of genome-wide gene expression data obtained from the peripheral white cells of UC and CD patients and evaluated clinically on an independent patient cohort. The test measures the expression levels of a discrete set of genes with biologic roles consistent with the pathophysiologic differentiation of UC and CD, and has an overall accuracy of 90%.
Keywords Inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), gene expression biomarkers, UC/CD differential diagnosis
Disclosure: The authors are employees of Exagen Diagnostics. The authors each have less than a 5% interest in the company. Acknowledgments: The authors gratefully acknowledge the contributions of the patients who consented to participate in this study. Received: September 20, 2010 Accepted: October 19, 2010 Citation: US Gastroenterology & Hepatology Review, 2010;6:65–8 Correspondence: Lisa M Davis, PhD, Exagen Diagnostics, Inc., 801 University Blvd SE, Albuquerque, NM 87106; E:
ldavis@exagen.com
Support: The publication of this article was funded by Exagen Diagnostics, Inc.
Inflammatory bowel disease (IBD) consists of a group of gastrointestinal tract disorders characterized by a chronic relapsing and remitting pattern of inflammation. IBD symptoms typically begin between the ages of 15 and 40 and affect more than one million people in the US.1,2 Multiple factors have been implicated in the pathophysiology of IBD, including processes in the immune system, environmental influences, and genetic predisposition. The two major types of IBD—ulcerative colitis (UC) and Crohn’s disease (CD)—differ in the extent and location of inflammation within the intestinal tract and, to varying degrees, in their symptoms, treatments, and long-term outcomes.
The differential diagnosis of UC and CD is based on a combination of the history and physical exam, laboratory tests, endoscopy, radiology, and pathology findings; there is currently no gold standard laboratory test. There is clearly a need for better and less invasive diagnostic tests. Currently available laboratory tests are summarized, including a recently developed gene expression-based test.
Diagnostic Pathology
Direct visualization by endoscopy is the gold standard diagnostic method for IBD. Combined with histopathologic evaluation of biopsies, it is the basis for differentiation between CD and UC. While the site of disease in UC is restricted to the colon, Crohn’s frequently presents
© TOUCH BRIEFINGS 2010
with ileal involvement. The extent and depth of ulcerations are also important components of the diagnostic evaluation. Taken together, these data are not always sufficient for distinguishing between CD and UC. Laboratory testing can provide additional supporting data to confirm diagnosis.
Conventional Clinical Laboratory Tests There are only a few minimally invasive laboratory tests used and studied for the diagnosis of IBD, including differentiation of CD from UC. Examples include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, serologic testing and lactoferrin. Molecular testing approaches represent an important step forward.3
Serology
Serum antibodies directed against mannan, a yeast cell-wall component (anti-Saccharomyces cerevisiae antibody)4,5
with neutrophil granules (anti-neutrophil cytoplasmic antibody)6 useful for diagnosing IBD and differentiating UC and CD.7,8
and autoantibodies reactive are
Their main
benefit appears to lie in the evaluation of patients with a moderate pre-test probability for IBD, in conjunction with endoscopic and/or radiologic studies.9,10
membrane protein (anti-OmpC),11
Serum antibodies directed against a bacterial outer a bacterial DNA fragment (I2),12,13
and 65
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