Mucos.Gene Express. Distinguishes UC From Colon-Only CD in Treatm.-Naïve Ped.pat

[dr.j.cardey@wanadoo.fr]

Mucosal Gene Expression Distinguishes Ulcerative Colitis From Colon-Only Crohn’s Disease in Treatment-Naïve Pediatric Patients

TAKE-HOME MESSAGE
•Rectal mucosal samples from 138 treatment-naïve children with inflammatory bowel disease affecting the rectum and 49 healthy controls were analyzed to determine mRNA expression patterns. Increased expression of mRNAs associated with a type 2 immune response and a type 17 immune response was seen in patients with ulcerative colitis (UC) compared with patients with colon-only Crohn’s disease (CD). Increased expression of IL-5 and IL-17A mRNAs could be used to differentiate UC from colon-only CD. In addition, gene expression patterns could be used to predict clinical response and remission in patients with UC.

•In children with untreated IBD, gene expression patterns in rectal mucosal tissue can be used to differentiate UC from colon-only CD and predict treatment response in patients with UC.

abstract

BACKGROUND & AIMS
There is controversy over the role of the type 2 immune response in pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naïve patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are upregulated in treatment-naïve pediatric patients with UC, compared to patients with Crohn’s disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels associate with clinical outcomes.

METHODS
We used a real-time reverse transcription quantitative PCR array to analyze mRNA expression patterns in rectal mucosal samples from 138 treatment-naïve pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 and 2012. Results were validated in real-time reverse transcription quantitative PCR analyses of rectal RNA from and independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children’s Hospital Medical Center.

RESULTS
We measured significant increases in mRNAs associated with a type 2 immune response (interleukin 5 gene [IL5], IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared to patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P=.001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (OR, 6.469; 95% CI, 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132-25.12).

CONCLUSION
In an analysis of rectal tissues from treatment-naïve pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC.

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