HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases

J Intern Med. 2023 May;293(5):648-655. doi: 10.1111/joim.13616. Epub 2023 Feb 26.


Background: Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti-drug antibody (ADAb) formation to infliximab.

Methods: Immune-mediated inflammatory disease patients on infliximab therapy (n = 612) were included. Neutralising ADAb were assessed with a drug-sensitive assay. Next generation sequencing-based HLA typing was performed.

Results: Overall, 147 (24%) patients developed ADAb. Conditional analyses indicated HLA-DQB1 (p = 1.4 × 10-6 ) as a primary risk locus. Highest risk of ADAb was seen when carrying at least one of the HLA-DQ2 haplotypes; DQB1*02:01-DQA1*05:01 or DQB1*02:02-DQA1*02:01 (OR 3.18, 95% CI 2.15-4.69 and p = 5.9 × 10-9 ). Results were consistent across diseases and when adjusting for concomitant immunomodulator. Computational predictions indicated that these HLA-DQ2 haplotypes bind to peptide motifs from infliximab light chain.

Conclusion: A genome-wide significant association between two HLA-DQ2 haplotypes and the risk of ADAb formation to infliximab was identified, suggesting that HLA-DQ2 testing may facilitate personalised treatment decisions.

Keywords: autoimmune disease; gastroenterology; genetics; immunology; immunosuppressive treatment; rheumatology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antibody Formation*
  • Celiac Disease*
  • Genetic Predisposition to Disease
  • HLA-DQ alpha-Chains / genetics
  • Haplotypes
  • Humans
  • Infliximab / therapeutic use


  • Infliximab
  • HLA-DQ alpha-Chains