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Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility
Arie Levine1, Subra Kugathasan, Vito Annese
1Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. alevine@wolfson.health.gov.il
Insights
Pediatric Crohn's disease (CD) location varies by age and NOD2/CARD15 gene mutations. Young children without these mutations show isolated colitis, while those with mutations have more ileocolitis.
Area of Science:
- Gastroenterology
- Genetics
- Pediatric Medicine
Background:
- Pediatric onset Crohn's disease (CD) presents differently than adult CD, with more colitis and less ileitis.
- Age-related differences in disease location may indicate distinct genetic or host response factors.
Purpose of the Study:
- To investigate the relationship between age of onset, NOD2/CARD15 mutations, and disease location in pediatric CD.
- To identify specific phenotypes associated with genetic factors in early-onset CD.
Main Methods:
- Analysis of 721 pediatric CD patients from three cohorts with high NOD2/CARD15 mutation frequency.
- Exclusion of patients with isolated upper intestinal disease, focusing on 678 remaining patients.
- Evaluation of interactions between age, NOD2/CARD15 status, and disease distribution (colitis, ileitis, ileocolitis).
Main Results:
- An age-related tendency for isolated colitis was observed, particularly in younger children without NOD2/CARD15 mutations (P = 4.57 x 10(-5)).
- Among pediatric CD patients with NOD2/CARD15 mutations, ileocolitis was more common under age 10, shifting to isolated ileitis over age 10 (P = 0.016).
- NOD2/CARD15 mutations were not found to be associated with the age of disease onset.
Conclusions:
- In early-onset pediatric CD, NOD2/CARD15 mutations are linked to a higher prevalence of ileocolitis and less isolated ileitis.
- Isolated colonic disease in very young children without NOD2/CARD15 mutations suggests a specific genetic influence on early-onset CD phenotypes.
Background:
Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon.
Methods:
We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location.
Results:
We found an age-related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first-decade onset patients (P = 4.57 x 10(-5), odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72-4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset.
Conclusions:
In early-onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early-onset disease.
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