Altered T cell receptor beta repertoire patterns in pediatric ulcerative colitis

Area of Science:

• Immunology
• Gastroenterology
• Genomics

Background:

• T cell receptor (TCR) diversity dictates immune specificity.
• Inflammatory bowel disease (IBD) involves immune dysregulation, but TCR repertoire alterations in pediatric ulcerative colitis (UC) are understudied.
• High-throughput sequencing (HTS) enables detailed TCR repertoire analysis.

Purpose of the Study:

• To investigate TCR-β repertoire differences between pediatric UC patients and healthy controls.
• To determine if TCR repertoires are altered in the gut of UC patients.
• To correlate TCR repertoire features with UC disease severity.

Main Methods:

• Collected paired blood and rectal samples from nine treatment-naive pediatric UC patients and four healthy controls.
• Utilized HTS to analyze the TCR-β repertoire in DNA from these samples.
• Compared TCR repertoire diversity, clonal expansion, and blood-rectal sample overlap between groups.

Main Results:

• UC patients exhibited significant TCR-β clonal expansion in the gut.
• A negative correlation was found between disease severity and gut TCR repertoire diversity.
• Distinct TCR repertoire patterns segregated severe UC, mild-moderate UC, and healthy controls.
• Higher blood-rectal TCR overlap was observed in UC patients compared to controls.
• Shared clonotypes were identified across multiple UC patients in the colon.

Conclusions:

• Pediatric UC is associated with expanded and altered TCR-β repertoires in the gut.
• TCR clonotypes in the colon are implicated in UC pathogenesis and correlate with disease severity.
• These findings highlight the role of T cells in mediating intestinal inflammation in pediatric UC.