Immunogenetic phenotypes in inflammatory bowel disease

or pathologic immune response to resident luminal bacterial constituents. Predisposing factors are genetic dysregulation of mucosal immune responses and/or barrier function, with onset triggered by environmental stimuli. These factors and their interactions may also be important determinants of disease phenotype and disease progression. The interaction between genetic susceptibility and luminal bacteria deserves particular attention. The results from animal studies indicate that not all commensal bacterial species are identical in their abilities to induce disease in the face of a common genetic defect. For instance, HLA B27/2 microglobulin transgenic rats raised under sterile conditions do not develop colitis. However, when colonized with normal specific pathogen-free commensal cecal bacteria, they develop aggressive disease involving the colon and gastroduodenal area within one month [1] . On the one hand, when colonized with a single bacterial strain, Bacteroides vulgatus, these same genetically susceptible rats develop moderate colitis but no gastro-duodenal disease. When selectively colonized with Eschericia.coli, they exhibit neither disease nor T cell activation [2] . This data suggests that not all commensal bacterial strains trigger an abnormal immune response for a given genetic susceptibility. The same non-pathogenic bacteria, however, may induce inflammation in a different genetically susceptible host. More specifically, further research from the same group demonstrated that Escherichia coli induced only mild cecal inflammation after 3 wk of monoassociation in interleukin 10-/-mice. In contrast, Enterococcus faecalismonoassociated interleukin 10-/-mice developed distal colitis at 10-12 wk that was progressively more severe and associated with duodenal inflammation and obstruction by 30 wk. Their results suggest that different commensal bacterial species selectively initiate immune-mediated intestinal inflammation with distinctly different kinetics and anatomic distribution in the same host [3] . These findings highlight the fact that both genetic susceptibility and luminal antigenic drive are important determinants of disease susceptibility and modification. Immune reactivity as measured by the serological expression of immune responses to specific bacteria may indeed be representative of this host gene luminal bacterial interaction. If indeed these immune responses represent the sum of a genetic and environmental predisposition to IBD, quantitative and qualitative expression of these immune responses may serve as an immunologic risk marker for IBD phenotypes.