Ethnic divergence in human leukocyte antigen-linked immunogenicity in inflammatory bowel disease

Table 1 Summary of human leukocyte antigen alleles associated with anti-drug antibody formation across ethnic groups in inflammatory bowel disease

HLA allele	Class	Ethnic group	Biologic	Key finding/ADA risk	Ref.
HLA-DQA1*05 (group)	II	European	IFX, ADA	HR = 1.90 (95%CI: 1.60-2.25); 92% ADA rate at 1 year with IFX monotherapy in carriers	Sazonovs et al[10]
HLA-DQA1*05:01	II	European	IFX	Specifically shortens time-to-LoR to infliximab; actionable by switching to adalimumab monotherapy	Hodges et al[13]; Ternette et al[14]
HLA-DQA1*05:05	II	European	IFX, ADA	Shortens time-to-LoR to both IFX and ADA; mitigated by concomitant immunomodulator (number needed to treat approximately 5 to prevent one drug-clearing ADA)	Hodges et al[13], Ternette et al[14]
HLA-DQB1*03:01	II	Japanese	IFX	HR = 2.03 (P = 9.42 × 10-5) for IFX discontinuation; subsumes DQA1*05:05 information in Japanese patients	Osaka et al[15]
HLA-C*03:04:01	I	Taiwanese	IFX	31.6% of ADA-positive vs 0% of ADA-negative patients (P = 0.02); prior autoimmune associations	Weng et al[19]
HLA-B*15:18:01	I	Taiwanese	ADA	66.7% of ADA-positive vs 0% of ADA-negative patients (P = 0.016); linked to Drug-Induced Liver Injury and aplastic anaemia outcomes	Weng et al[19]
HLA-DQA1*05 (group)	II	Taiwanese (25.3% allele frequency)	IFX, ADA	No significant association with ADA formation despite comparable carriage frequency; fails to predict in this cohort	Weng et al[19]; Pascual-Oliver et al[7]

ADA: Anti-drug antibodies; HLA: Human leukocyte antigen; HR: Hazard ratio; IFX: Infliximab; LoR: Loss of response.