Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally invasive tests for IBD diagnosis and/or prognosis as well as assessment of disease activity and response to therapy. Here, we update the current status of IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA [miRNA]) biomarkers. As an update, the classical serological biomarkers, including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan antibodies, are discussed only briefly. Emphasis in this article is given to those that have been recently identified or extensively characterized, as well as to the clinical utilities of biomarkers, with special attention to prediction of disease complication and activity assessment, mucosal healing, and response to therapies. In particular, we discuss the utilities of blood-based biomarkers predicting therapeutic response to anti-tumor necrosis factor (TNF)-alpha, such as anti-anti-TNF alpha antibodies or anti-drug antibodies (ADA) and trough level of anti-TNF alpha. Fecal biomarkers, which have recently attracted substantial attention, are also discussed extensively, including the well-characterized calprotectin and lactoferrin, as well as the recently characterized M2-PK, CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the discovery of a number of rare yet disease-defining IBD-susceptible genes, particularly those involved in very early onset IBD, providing rare yet extremely useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we briefly summarize the discovery, characterization, and potential implications of miRNA as potential IBD biomarkers.