Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease.

BACKGROUND: Presenting features of inflammatory bowel disease (IBD) are non-specific. We hypothesized that mRNA profiles could (1) identify genes and pathways involved in disease pathogenesis; (2) identify a molecular signature that differentiates IBD from other conditions; (3) provide insight into systemic and colon-specific dysregulation through study of the concordance of the gene expression. METHODS: Children (8-18 years) were prospectively recruited at the time of diagnostic colonoscopy for possible IBD. We used transcriptome-wide mRNA profiling to study gene expression in colon biopsies and paired whole blood samples. Using blood mRNA measurements, we fit a regression model for disease state prediction that was validated in an independent test set of adult subjects (GSE3365). RESULTS: Ninety-eight children were recruited [39 Crohn's disease, 18 ulcerative colitis, 2 IBDU, 39 non-IBD]. There were 1,118 significantly differentially (IBD vs non-IBD) expressed genes in colon tissue, and 880 in blood. The direction of relative change in expression was concordant for 106/112 genes differentially expressed in both tissue types. The regression model from the blood mRNA measurements distinguished IBD vs non-IBD disease status in the independent test set with 80% accuracy using only 6 genes. The overlap of 5 immune and metabolic pathways in the two tissue types was significant (p<0.001). CONCLUSIONS: Blood and colon tissue from patients with IBD share a common transcriptional profile dominated by immune and metabolic pathways. Our results suggest that peripheral blood expression levels of as few as 6 genes (IL7R, UBB, TXNIP, S100A8, ALAS2, and SLC2A3) may distinguish patients with IBD from non-IBD.

Potential role of IGF-1 z score to predict permanent linear growth impairment in children with IBD.

In this pilot study, we analyzed serum insulin-like growth factor 1 (IGF-1)- and IGF-binding protein-3-for-age z scores from 54 inflammatory bowel disease children with no, temporary, or permanent growth impairment. Although our findings did not reach statistical significance, patients with permanent linear growth impairment had lower IGF-1-for-age z scores (-1.76 [-2.25 to -0.43]) compared with those with no or temporary growth impairment (-0.84 [-1.49 to -0.3]) and -1.16 [-1.59 to -1.51], respectively). IGF-binding protein-3 levels were similar across the 3 groups. In the absence of significant inflammation and malnutrition, lower IGF-1-for-age z scores may help distinguish patients likely to have permanent growth impairment from those whose growth impairment is likely to be temporary.

Late adolescent linear growth pattern in pediatric-onset inflammatory bowel disease.

The late adolescent linear growth pattern of pediatric patients with inflammatory bowel disease (IBD) has rarely been studied. We retrospectively reviewed the height measurements of 475 patients with IBD at 16, 18, and 20 years old for girls, and 18 and 20 years old for boys. We also compared Bayley-Pinneau bone age-predicted and -measured adult heights. Female patients had mean height-for-age z scores of -0.25 ± 1.0 at 16 years and -0.23 ± 1.0 at 18 years (P = 0.189); boys had z scores of -0.30  ± 1.1 at 18 years and -0.26 ± 1.0 at 20 years, respectively (P = 0.105). Bayley-Pinneau height predictions were 1.5 and 2.4 cm greater than measured height for 18-year-old girls (P = 0.060) and 20-year-old boys (P = 0.017), respectively. Our data indicate that most patients with IBD attain adult height within normal timing for the population. Hence, early identification of growth impairment is critical to appropriate management in IBD.