摘要
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 Taiwan Region of China 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 Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,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 Taiwan Region of China 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.
基金
Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226
Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017
The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
