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Interferon γ Expressing Mucosal Cells in Pediatric Chronic Inflammatory Bowel Disease
1Department of Pathology, British Columbia Children's and Women's Hospitals, Vancouver, BC, Canada.
Insights
Interferon gamma (IFNγ) levels in the gut lining may help distinguish Crohn's disease (CD) from ulcerative colitis (UC). Increased IFNγ was observed in CD ileum and in the colon for both conditions, but overlap limits its diagnostic use.
Area of Science:
- Gastroenterology
- Immunology
- Pathology
Background:
- Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases with distinct treatments and prognoses.
- Differentiating CD and UC can be challenging due to overlapping clinical and histological features.
- Aberrations in gastrointestinal mucosal inflammatory cells are implicated in CD and UC pathogenesis.
Purpose of the Study:
- To investigate the diagnostic utility of Interferon gamma (IFNγ) immunohistochemical expression in differentiating pediatric CD and UC.
- To assess IFNγ expression in various gastrointestinal mucosal sites (stomach, duodenum, terminal ileum, colon).
Main Methods:
- Automated assessment of IFNγ-positive mucosal cells in archival GI biopsies from a pediatric cohort.
- Comparison of IFNγ expression between CD, UC, and normal controls across different gastrointestinal segments.
Main Results:
- IFNγ-positive cells were elevated in the colon of both CD and UC patients compared to controls.
- IFNγ-positive cells were increased in the ileum of CD patients compared to controls and UC patients.
- IFNγ abundance did not correlate with active inflammation, suggesting it's an independent marker.
Conclusions:
- IFNγ immunohistochemistry shows potential as a biomarker for differentiating CD and UC, particularly in the ileum.
- Significant overlap in IFNγ expression between CD, UC, and normal tissues suggests limited clinical utility in routine diagnosis.
- Further research is warranted to explore IFNγ's role in specific cases, such as indeterminate inflammatory bowel disease.
Abstract:
The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) is multifactorial and includes aberrations in the composition of gastrointestinal mucosal inflammatory cells. Accurate identification of CD and UC is important as treatment and prognosis differs; however, CD and UC may be difficult to differentiate. Interferon γ (IFNγ) expression appears to be increased in ileal mucosa from CD patients, implying that IFNγ could be a diagnostically useful marker to differentiate CD from UC. This study uses automated assessment of IFNγ immunohistochemical expression in archival GI mucosal biopsies from stomach, duodenum, terminal ileum, and colon in a pediatric population to address this possibility. IFNγ positive mucosal cells are increased in the colon in both CD and UC compared to normal colon and in the ileum of CD compared to normal and UC. The abundance of IFNγ positive cells is not correlated with the presence of active inflammation, indicating that active inflammation is not responsible for the variance in abundance of IFNγ positive cells between cohorts and sites. Overlap between CD, UC, and normal suggests that IFNγ immunohistochemistry may only be clinically useful in select situations such as undetermined inflammatory bowel disease and additional study in these areas is warranted.
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