Gene expression profiles of late colonic Crohn's disease

To determine the genetic program mediating and maintaining the change from susceptibility to Crohn's disease (CD) to ongoing tissue destruction and loss of function, we utilized Affymetrix HG U95 AV2 Gene Chips and analyzed unpooled surgical CD colon specimens from adult patients. Using the patient as his own genetic filter we examined involved versus uninvolved adjacent areas, comparing results within one individual and then performing analysis comparing results between four individuals. Our results interrogated twice as many genes than the previous studies that used pooled unmatched specimens. We identified a limited set of nine genes upregulated in all four patients, and one gene (PTN) as downregulated. Several of the genes, including DEFA6, PAP, REG1A, REG1B, and phospholipase A2 had been implicated in previous studies, supporting their key role in CD. In 3 of 4 patients, 24 genes were upregulated in diseased areas, including DEFA5, IL-8, MMP-1, S100 calcium binding protein, and MGSA. Additional new candidate genes were identified, including DMT1, SERPINA1, GW112, and iNOS. The use of the unpooled samples allowed the detection of significant interindividual differences in expression of many other genes, supporting disease heterogeneity in CD. Results with select genes were confirmed with RT-PCR studies, as well as on biopsy samples from pediatric patients. We have determined a common profile of "late" CD, and also demonstrated the potential variability, suggesting possible differences in etiology, triggers, and the need for more individualized management. Additional studies to investigate protein expression of these candidate genes should be undertaken.