Towards a novel molecular classification of IBD.

Classifying IBD patients is important for decisions on the intensity of follow-up, therapy and mode of delivery. The most recent classification of Crohn's disease (CD) and ulcerative colitis (UC), the Montreal classification, is based on clinical grounds: for CD, the age at diagnosis and disease location and behavior and for UC, the age at diagnosis and the extent of disease. During the Working Party in 2005 in Montreal, it was judged by the panel of experts that a molecular reclassification using serology and/or genetic markers was too premature and not yet justified. In the meanwhile, the number of genes associated with IBD has increased to >100 and more antimicrobial peptides have also been identified. We recently showed that genetic variants enable the classification of CD patients in distinct clusters, which is different from clusters seen in healthy individuals. Furthermore, there was a poor relationship between the genetic-based subgroups and the clinical subphenotypes being used. The promising role for molecular markers lies most likely in disease stratification, the prediction of prognosis at the time of diagnosis and the prediction of therapy outcome. The behavior of CD and UC varies between patients, and the characteristic transmural inflammation in CD--when untreated--will often progress and lead to stricture or fistula formation over time. Predicting which patients are at risk for progression to complications and how fast this occurs could have therapeutic implications, as more aggressive treatment strategies could become defendable in the appropriate patient. Genetic factors are definitively more appealing for risk stratification on more solid grounds. Molecular markers may also better explain changes in disease behavior from a pathogenic standpoint, and by combining several markers this strategy can approach clinical utility. Before starting to apply molecular markers to predict disease behaviors, tools should be made available to score disease progression. Only then could the value of molecular markers to predict the speed of progression be fully explored in prospective studies.