Transcription and DNA Methylation Patterns of Blood-Derived CD8⁺ T Cells Are Associated With Age and Inflammatory...

Area of Science:

• Immunology
• Gastroenterology
• Genomics

Background:

• CD8+ T cell gene expression patterns have been linked to clinical outcomes in adult inflammatory bowel diseases (IBD).
• Validation in independent cohorts is crucial for clinical application of biomarkers.
• Previous findings require independent confirmation to ensure reliability.

Purpose of the Study:

• To validate previously reported CD8+ T-cell gene expression signatures as prognostic biomarkers in pediatric and adult IBD cohorts.
• To investigate the association between CD8+ T-cell gene expression and DNA methylation with IBD diagnosis and outcomes.
• To assess the reproducibility of CD8+ T-cell signatures across different patient cohorts.

Main Methods:

• Analysis of peripheral blood samples from 112 children with new IBD diagnoses and 19 controls.
• Genome-wide transcription and DNA methylation profiling of CD8+ T cells.
• Integration of data from publicly available adult IBD patient cohorts.

Main Results:

• Previously reported CD8+ T-cell prognostic and exhaustion signatures were not detected in pediatric or second adult IBD cohorts.
• CD8+ T-cell gene expression was associated with age and sex across cohorts.
• CD8+ T-cell gene transcription correlated with IBD presence when non-IBD controls were included.
• DNA methylation in CD8+ T cells from pediatric Crohn's disease patients correlated with age, not disease outcome.

Conclusions:

• Previously reported associations between CD8+ T-cell gene transcription and IBD disease outcome could not be validated.
• Findings underscore the difficulties in developing robust prognostic biomarkers for IBD.
• Emphasizes the critical need for validation in large, independent cohorts before clinical implementation.