HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases.
J Intern Med
; 293(5): 648-655, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36843323
ABSTRACT
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*0201-DQA1*0501 or DQB1*0202-DQA1*0201 (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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença Celíaca
/
Formação de Anticorpos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Intern Med
Assunto da revista:
MEDICINA INTERNA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Noruega