HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children

Area of Science:

• Genetics
• Immunology
• Pediatric Gastroenterology

Background:

• The human leukocyte antigen (HLA) allele group HLA-DQA1*05 is a known risk factor for ulcerative colitis (UC) and is associated with anti-infliximab antibodies in inflammatory bowel disease (IBD).
• Understanding the genotype-phenotype correlations of HLA-DQA1*05 in pediatric IBD is crucial for predicting disease course and treatment response.

Purpose of the Study:

• To investigate the association between the HLA-DQA1*05 allele and clinical characteristics at diagnosis and during disease flares in a pediatric IBD cohort.
• To explore potential genotype-phenotype relationships in children with UC and Crohn's disease (CD).

Main Methods:

• A multi-center cohort study in Poland involving 401 children with IBD (188 UC, 213 CD).
• Assessment of HLA-DQA1*05 status and detailed phenotyping at diagnosis and worst flare, including disease extent, severity scores (PUCAI), and treatment history.
• Statistical analysis to determine correlations between HLA-DQA1*05 status and various clinical parameters.

Main Results:

• HLA-DQA1*05 was present in 55.1% of pediatric IBD patients.
• In UC, HLA-DQA1*05 positivity was moderately associated with extensive colonic inflammation (E4) at diagnosis (p=0.012).
• In CD, HLA-DQA1*05 carriers were less likely to present with combined stenosing/penetrating disease (B2B3, p=0.048) or proximal small bowel disease (L4a, p=0.046) at worst flare.

Conclusions:

• The HLA-DQA1*05 allele influences the clinical phenotype of pediatric IBD, particularly affecting disease extent in UC and disease behavior in CD.
• These findings highlight the importance of genetic factors in shaping IBD presentation and may inform strategies for managing anti-TNF immunogenicity.