HLA-C*03:04:01 and HLA-B*15:18:01 but not HLA-DQA1*05 associated with anti- tumor necrosis factor antibody formation in Taiwanese inflammatory bowel disease patients
Journal
World Journal of Gastroenterology
Journal Volume
31
Journal Issue
41
Pages
111745
ISSN
2219-2840
Date Issued
2025-11-07
Author(s)
Lin, Wei-Chen
Lai, Sheng-Kai
Wang, Chun-Ying
Abstract
Background: Anti-drug antibodies (ADAs) can reduce the effectiveness of biologics. While human leukocyte antigen (HLA)-DQA1*05 allele is linked to ADA formation in European Crohn's disease patients, its relevance in non-European populations remains unclear.
Aim: To investigate HLA genotypes associated with the development of ADAs in Taiwanese inflammatory bowel disease (IBD) patients treated with biologics.
Methods: In this multicenter study, IBD patients treated with anti-tumor necrosis factor (TNF), anti-integrin, or anti-interleukin (IL)-12/23 therapies from April 2022 to June 2024 were enrolled. All participants underwent next-generation sequencing for HLA genotyping. ADA levels were measured via enzyme linked immunosorbent assay. HLA allele frequencies were compared between ADA-positive and ADA-negative groups, and against general Taiwanese population data.
Results: Ninety-five IBD patients were included: 58 received anti-TNF therapy (38 infliximab, 20 adalimumab), 27 anti-integrin, and 10 anti-IL-12/23. ADAs occurred only in the anti-TNF group (n = 22): 19 infliximab (50%) and 3 adalimumab (15%). No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents. HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs (31.6% vs 0%, P = 0.02), and HLA-B*15:18:01 with anti-adalimumab ADAs (66.7% vs 0%, P = 0.016). HLA-DQA1*05 was not associated with ADA formation. Frequencies of HLA-C*03:04:01 (8.4% vs 10.5%) and HLA-B*15:18:01 (1.6% vs 0.6%) in IBD patients were comparable to those in the general population. ADA titers were inversely correlated with serum drug levels.
Conclusion: In Taiwanese IBD patients, HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab, respectively. HLA-DQA1*05 was not predictive, highlighting ethnic differences in genetic predisposition to immunogenicity.
Subjects
Anti-drug antibodies
Anti-tumor necrosis factor therapy
Crohn’s disease
Human leukocyte antigen genotype
Inflammatory bowel disease
Ulcerative colitis
SDGs
Publisher
Baishideng Publishing Group Inc
Type
journal article