• Marthe Kirkesaether Brun, Kristin Hammersbøen Bjørlykke, Marte K Viken, Grethe-Elisabeth Stenvik, Rolf A Klaasen, Johanna E Gehin, David John Warren, Joseph Sexton, Øystein Sandanger, Tore K Kvien, Cato Mørk, Espen A Haavardsholm, Jørgen Jahnsen, Guro Løvik Goll, Benedicte A Lie, Nils Bolstad, Kristin Kaasen Jørgensen, and Silje Watterdal Syversen.
• Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
• J. Intern. Med. 2023 May 1; 293 (5): 648655648-655.

BackgroundImmunogenicity 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.MethodsImmune-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.ResultsOverall, 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.ConclusionA 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.© 2023 The Association for the Publication of the Journal of Internal Medicine.

16 keywords...

hide…