New IBD Markers: Definition of Disease Heterogeneity

Abstract

There is emerging evidence that serum and mucosal markers differentiate Crohn's disease from ulcerative colitis; moreover, subgroups can be defined within each disease. Subgroups have been defined on the basis of genetic, serum and mucosal markers, and are associated with different clinical phenotypes. Antineutrophil cytoplasmic antibodies (ANCA) define subgroups of patients with both ulcerative colitis and Crohn's disease. A new serum marker, 20P-1, has been found in 60 to 70% of patients with Crohn's disease, 20% of ulcerative colitis patients and approximately 10% of the normal control population. The 20P-1 marker further stratifies the subgroups of patients defined by ANCA. In addition to serum markers, genes regulating production of the cytokine tumour necrosis factor (TNF)-α have been shown to be different across ulcerative colitis and Crohn's disease, and within the ulcerative colitis group. Serum markers may reflect differential mucosal inflammatory responses as is best shown by ANCA. B cell clones within the mucosa of 60 to 70% of patients with ulcerative colitis produce ANCA spontaneously. Studies currently underway demonstrate different TNF- α production within the mucosa of patients with Crohn's disease compared with ulcerative colitis patients. Correlation studies with TNF-α microsatellites (genes) are being performed. These markers are the focus of a trial using molecularly engineered products that are capable of inhibiting TNF-α to identify patients likely to respond to anti-TNF therapy. In this constantly evolving climate of understanding and treating inflammatory bowel disease, serum, mucosal and genetic markers as well as genetic associations are being formed to determine clinical phenotypes that may be differentially responsive to very selected treatment modalities. These advances highlight the likelihood that the various markers define different types of mucosal inflammation. The different types of mucosal inflammation will determine the response or resistance to certain types of therapeutic options.