PMID- 36843323 OWN - NLM STAT- MEDLINE DCOM- 20230414 LR - 20230620 IS - 1365-2796 (Electronic) IS - 0954-6820 (Linking) VI - 293 IP - 5 DP - 2023 May TI - HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases. PG - 648-655 LID - 10.1111/joim.13616 [doi] AB - 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 x 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 x 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. CI - (c) 2023 The Association for the Publication of the Journal of Internal Medicine. FAU - Brun, Marthe Kirkesaether AU - Brun MK AUID- ORCID: 0000-0001-5148-9684 AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Bjorlykke, Kristin Hammersboen AU - Bjorlykke KH AUID- ORCID: 0000-0003-2369-6760 AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. AD - Department of Gastroenterology, Akershus University Hospital, Lorenskog, Norway. FAU - Viken, Marte K AU - Viken MK AUID- ORCID: 0000-0002-3917-9269 AD - Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. AD - Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. FAU - Stenvik, Grethe-Elisabeth AU - Stenvik GE AUID- ORCID: 0000-0002-2919-3999 AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. FAU - Klaasen, Rolf A AU - Klaasen RA AUID- ORCID: 0000-0002-6078-5108 AD - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. FAU - Gehin, Johanna E AU - Gehin JE AUID- ORCID: 0000-0002-9896-0223 AD - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. FAU - Warren, David John AU - Warren DJ AD - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. FAU - Sexton, Joseph AU - Sexton J AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. FAU - Sandanger, Oystein AU - Sandanger O AD - Section of Dermatology, Oslo University Hospital, Oslo, Norway. FAU - Kvien, Tore K AU - Kvien TK AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Mork, Cato AU - Mork C AD - Akershus Dermatology Center, Lorenskog, Norway. FAU - Haavardsholm, Espen A AU - Haavardsholm EA AUID- ORCID: 0000-0002-1427-4745 AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Jahnsen, Jorgen AU - Jahnsen J AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. AD - Department of Gastroenterology, Akershus University Hospital, Lorenskog, Norway. FAU - Goll, Guro Lovik AU - Goll GL AUID- ORCID: 0000-0002-8506-725X AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. FAU - Lie, Benedicte A AU - Lie BA AUID- ORCID: 0000-0002-1159-7004 AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. AD - Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway. AD - Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. FAU - Bolstad, Nils AU - Bolstad N AD - Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. FAU - Jorgensen, Kristin Kaasen AU - Jorgensen KK AUID- ORCID: 0000-0002-3693-7706 AD - Department of Gastroenterology, Akershus University Hospital, Lorenskog, Norway. FAU - Syversen, Silje Watterdal AU - Syversen SW AUID- ORCID: 0000-0003-2159-3696 AD - Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230226 PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - B72HH48FLU (Infliximab) RN - 0 (HLA-DQ alpha-Chains) SB - IM MH - Humans MH - Infliximab/therapeutic use MH - HLA-DQ alpha-Chains/genetics MH - *Antibody Formation MH - Genetic Predisposition to Disease MH - Haplotypes MH - Alleles MH - *Celiac Disease OTO - NOTNLM OT - autoimmune disease OT - gastroenterology OT - genetics OT - immunology OT - immunosuppressive treatment OT - rheumatology EDAT- 2023/02/28 06:00 MHDA- 2023/04/14 06:42 CRDT- 2023/02/27 01:33 PHST- 2023/04/14 06:42 [medline] PHST- 2023/02/28 06:00 [pubmed] PHST- 2023/02/27 01:33 [entrez] AID - 10.1111/joim.13616 [doi] PST - ppublish SO - J Intern Med. 2023 May;293(5):648-655. doi: 10.1111/joim.13616. Epub 2023 Feb 26.