Issa T, Issa I. Ethnic divergence in human leukocyte antigen-linked immunogenicity in inflammatory bowel disease. World J Gastroenterol 2026; 32(25): 115526 [DOI: 10.3748/wjg.115526]
Corresponding Author of This Article
Iyad Issa, MD, Department of Gastroenterology and Hepatology, Harley Street Medical Center, Marina Village, Villa No. A21, Abu Dhabi 41475, United Arab Emirates. iyadissa71@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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Issa T, Issa I. Ethnic divergence in human leukocyte antigen-linked immunogenicity in inflammatory bowel disease. World J Gastroenterol 2026; 32(25): 115526 [DOI: 10.3748/wjg.115526]
World J Gastroenterol. Jul 7, 2026; 32(25): 115526 Published online Jul 7, 2026. doi: 10.3748/wjg.115526
Ethnic divergence in human leukocyte antigen-linked immunogenicity in inflammatory bowel disease
Taly Issa, Iyad Issa
Taly Issa, Medical School, University of Nicosia, Nicosia 24005, Cyprus
Iyad Issa, Department of Gastroenterology and Hepatology, Harley Street Medical Center, Abu Dhabi 41475, United Arab Emirates
Author contributions: Issa T contributed to the discussion and design of the manuscript; Issa I designed the overall concept and outline of the manuscript; Issa I and Issa T contributed to this paper, the writing, and editing the manuscript, illustrations, and review of literature; all authors have read and approved the final manuscript
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Iyad Issa, MD, Department of Gastroenterology and Hepatology, Harley Street Medical Center, Marina Village, Villa No. A21, Abu Dhabi 41475, United Arab Emirates. iyadissa71@gmail.com
Received: October 20, 2025 Revised: January 2, 2026 Accepted: February 5, 2026 Published online: July 7, 2026 Processing time: 254 Days and 24 Hours
Core Tip
Core Tip: This opinion review contextualizes the landmark findings, which identified human leukocyte antigen (HLA)-C*03:04:01 and HLA-B*15:18:01 as ethnic-specific risk alleles for anti-drug antibody formation in Taiwanese inflammatory bowel disease (IBD) patients receiving infliximab and adalimumab, respectively, challenging the universality of HLA-DQA1*05 as a pharmacogenomic predictor of anti-tumor necrosis factor immunogenicity. We integrate these findings within: (1) The shifting global IBD epidemiology; (2) Four-digit allele subtype behavior in European and East Asian populations; (3) Mechanistic pathways including cross-presentation, peptide-groove structural specificity, and killer cell immunoglobulin-like receptor-mediated tolerance regulation; (4) The complementary roles of immunomodulator co-therapy and therapeutic drug monitoring; and (5) The broader precision pharmacogenomics agenda in IBD. Global multi-ethnic collaboration to validate allele-immunogenicity associations is an ethical and clinical imperative.
