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Short Ileal Microvillus Length Phenotype Associates with Progression from Inflammatory to Complicated Disease
Yael Haberman1,2, Tzipi Braun2, Rebekah Karns1
1Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Insights
Shorter ileal microvillus length (MVL) in pediatric Crohn's disease (CD) correlates with a higher risk of developing complicated disease behaviors. This finding suggests ileal MVL may serve as a prognostic biomarker for pediatric CD patients.
Area of Science:
- Gastroenterology
- Histopathology
- Pediatric Inflammatory Bowel Disease
Background:
- Previous studies identified ileal microvillus length (MVL) as a prognostic biomarker in adult Crohn's disease (CD).
- The prognostic value of ileal MVL in pediatric CD and its association with disease behavior remain unexplored.
Purpose of the Study:
- To investigate differences in ileal MVL between pediatric CD patients and controls.
- To assess the association between ileal MVL and stricturing or penetrating disease behaviors in pediatric CD.
Main Methods:
- Ileal microvillus length (MVL) was determined from histology samples of 412 pediatric CD patients and 88 controls.
- Associations between MVL, clinical data, RNA-seq profiles, and histopathology were analyzed in the RISK cohort with >60 months follow-up.
Main Results:
- Pediatric CD patients exhibited significantly shorter ileal MVL compared to controls.
- Shorter ileal MVL was associated with an increased risk and earlier onset of complicated disease behaviors.
- Ileal MVL correlated with molecular signatures and histopathological scores, indicating altered brush border function and inflammation.
Conclusions:
- Short ileal MVL is a significant indicator of complicated disease behavior development in pediatric Crohn's disease.
- Ileal MVL shows potential as a histological biomarker for predicting disease prognosis in pediatric CD.
Background And Aims:
Our previous studies of adult Crohn's disease (CD) suggested ileal microvillus length (MVL) as a prognostic biomarker for therapy response. We investigated if ileal MVL also differed in pediatric CD versus controls and tested for associations with stricturing or penetrating disease behavior outcomes.
Methods:
We determined the average ileal MVL of 412 CD and 88 control H&E-stained ileal histology samples from a subset of the RISK cohort and 2 validation cohorts. The RISK sub-cohort had an average follow-up of >60 months and was used to test for associations between ileal MVL and clinical data, RNA-seq molecular profiles, and histopathological scores.
Results:
Ileal MVL was shorter in CD relative to control (median of 1.396 µm vs. 1.598 µm, respectively). Ileal MVL generally did not associate with demographics or clinical disease activity indices. However, there was a significant association between shorter ileal MVL and increased risk of development of complicated disease behavior. Furthermore, CD samples with shorter ileal MVL showed a significantly shorter time to development of complicated disease behavior. Ileal MVL positively associated with a gene signature enriched for brush border membrane and negatively associated with a gene signature enriched for extracellular matrix, inflamed macrophages, and fibroblasts. Accordingly, ileal MVL was negatively correlated with histopathological scores.
Conclusions:
Short ileal MVL is associated with the development of complicated disease behaviors in pediatric CD, supporting the potential use of this histological phenotype as a biomarker for CD prognosis.
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