HLA-DQB1*03:01 and HLA-DQA1*05:05 as key genetic determinants of infliximab response and immunogenicity in Japanese patients with inflammatory bowel disease.

BACKGROUND

Specific human leukocyte antigen (HLA) genotypes, particularly HLA-DQA1*05, have been proposed as predictors for infliximab (IFX) treatment response and immunogenicity in Western populations. However, the evidence regarding the effect of HLA-DQA1*05 remains limited in East Asian populations, including in Japan. Moreover, HLA-DQA1*05 frequency differs substantially from those in Western populations. Comprehensive analyses of the association between HLA alleles and IFX treatment outcomes may contribute to the identification of novel prognostic markers for IFX therapies.

METHODS

We retrospectively analyzed 301 biologic-naïve Japanese patients with inflammatory bowel disease (IBD). IFX persistence was assessed at both 2-digit and 4-digit HLA allele resolutions, and associations with anti-drug antibody levels at 1 year after the initiation of IFX therapy were evaluated.

RESULTS

At the 2-digit resolution analysis, HLA-DQB1*03 (hazard ratio [HR] = 2.39, p = 1.89E-06) and HLA-DQA1*05 (HR = 1.99, p = 3.91E-04) were significantly associated with early IFX discontinuation. At the 4-digit resolution analysis, HLA-DQB1*03:01 (HR = 2.03, p = 9.42E-05) and HLA-DQA1*05:05 (HR = 2.18, p = 4.42E-05) showed similar associations. All HLA-DQA1*05:05 alleles formed haplotypes with HLA-DQB1*03:01. Importantly, HLA-DQB1*03:01 was also associated with early discontinuation of IFX even when it formed haplotypes with alleles other than HLA-DQA1*05:05. Both HLA-DQB1*03:01 and HLA-DQA1*05:05 were significantly associated with elevated anti-drug antibody levels (p = 3.23E-03 and 3.54E-03, respectively).

CONCLUSIONS

HLA-DQB1*03:01 encompasses the information of HLA-DQA1*05:05 and serves as a strong genetic predictor of IFX treatment persistence and immunogenicity in Japanese patients with IBD, offering a potential biomarker for personalized therapy.