Journal of Pediatric Gastroenterology & Nutrition:
North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Annual Meeting, October 19-22, 2006, Orlando, Florida: Abstracts: POSTER SESSION III, SATURDAY, OCTOBER 21, 2006, 7:45 a.m. - 9:45 a.m.: Intestine/Colon/IBD: 133
GENE EXPRESSION PROFILES DEFINE SUBTYPES OF PEDIATRIC CROHN'S COLITIS AT DIAGNOSIS
Carey, Rebecca; Han, Xiaonan; Bonkowski, Erin; Denson, Lee
Cincinnati Childrens Hospital Medical Center, Cincinnati, OH.
There are currently no validated methods for predicting clinical course in Crohn's disease (CD). We hypothesized that disease course in CD would correlate with differing gene expression profiles from the affected colon at diagnosis.
Colon biopsies and serum were obtained from nine children with CD at diagnosis, five children with a history of active CD despite treatment (refractory) and eight healthy controls. RNA was prepared from colon biopsies and gene expression was determined using the Affymetrix Human Genome U133 array, with analysis performed using GeneSpring™ software. Serum cytokine levels were measured using the Bioplex™ assay. A retrospective chart review was performed to gather demographic and clinical data.
Age, sex, disease distribution, endoscopic severity, and biochemical data did not differ between CD patients at diagnosis and the treatment refractory group. Serum IL-6 and activation of the IL-6 dependent transcription factor, STAT3, were up regulated in both CD groups compared to controls. Moreover, gene array analysis revealed that STAT3 target genes including CXCL chemokines, MMPs, and factors which regulate cell proliferation and survival were up regulated in both groups. The treatment refractory group additionally exhibited up regulation of a broad array of immune and tissue remodeling networks involving CCL chemokines, TLRs, eotaxin, and multiple collagen subtypes. Five patients at diagnosis had gene expression profiles similar to the broad immune activation seen in treatment refractory CD. Patients with the refractory profile at diagnosis were more likely to have higher serum IL-8 and IL-1β levels and to be steroid dependent during the first year after diagnosis.
Distinct serum cytokine and colon gene array profiles at diagnosis may be associated with different clinical courses in children with CD. If confirmed by a larger ongoing study, this may allow for more targeted therapy in patients likely to have a refractory course.
© 2006 Lippincott Williams & Wilkins, Inc.