Genetic Profiling in Inflammatory Bowel Disease: From Association to Bedside

Abstract

The chronic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), encompass a wide spectrum of diseases, characterized by both intestinal and extra-intestinal manifestations. From the early days of IBD genetic studies, the goals have included identification of healthy relatives at high risk of disease development and recognition of patients at risk for a severe disease course. To make progress on the path to personalized medicine, genetic polymorphisms or stable biomarkers are highly sought after in the profiling of IBD patients. A genetic test with high specificity has the potential to alter the treatment course of a subset patients, as shown in the case of thiopurine S-methyl transferase genotyping.1 At present, it is impossible to confidently predict a patient’s future disease burden.2 In referral center studies, certain clinical features are indicative of a more complicated disease (younger age at diagnosis, perianal disease, steroid requirement at diagnosis [CD], endoscopic severity of ulcerations and inability to achieve mucosal healing [CD/UC]), but their therapeutic application in patient stratification for “top‐down” strategies is still debated.3 Considering that mucosal healing is overtaking symptoms as the real therapeutic goal, with a true potential for modification of the disease course, diagnostic tests, able to accurately predict the mucosal response to treatment and the longevity of this response, will be required to successfully personalize treatment. 4 Biomarkers like C-reactive protein are proving useful in monitoring disease activity (including mucosal healing) in patients treated with infliximab and early normalization of C-reactive protein correlates with long-term response. 5 The utility of biomarkers (including fecal calprotectin and serum antiglycan antibodies) was the subject of a recent GASTROENTEROLOGY review. 6 In this article, we outline how some of the recent advances in our understanding of the genetic susceptibility to IBD may start to impact on therapy of our patients.