Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis
Abstract HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42324-6 |
| _version_ | 1797576696143020032 |
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| author | Mariko Inoue Yasuo Nagafuchi Mineto Ota Haruka Tsuchiya Shoko Tateishi Hiroko Kanda Keishi Fujio |
| author_facet | Mariko Inoue Yasuo Nagafuchi Mineto Ota Haruka Tsuchiya Shoko Tateishi Hiroko Kanda Keishi Fujio |
| author_sort | Mariko Inoue |
| collection | DOAJ |
| description | Abstract HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy. |
| first_indexed | 2024-03-10T21:57:23Z |
| format | Article |
| id | doaj.art-56cbc4b0b6a841e8ad9bc7ba693420e6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:57:23Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-56cbc4b0b6a841e8ad9bc7ba693420e62023-11-19T13:05:03ZengNature PortfolioScientific Reports2045-23222023-09-011311910.1038/s41598-023-42324-6Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritisMariko Inoue0Yasuo Nagafuchi1Mineto Ota2Haruka Tsuchiya3Shoko Tateishi4Hiroko Kanda5Keishi Fujio6Department of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoAbstract HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.https://doi.org/10.1038/s41598-023-42324-6 |
| spellingShingle | Mariko Inoue Yasuo Nagafuchi Mineto Ota Haruka Tsuchiya Shoko Tateishi Hiroko Kanda Keishi Fujio Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis Scientific Reports |
| title | Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis |
| title_full | Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis |
| title_fullStr | Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis |
| title_full_unstemmed | Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis |
| title_short | Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis |
| title_sort | carriers of hla drb1 04 05 have a better clinical response to abatacept in rheumatoid arthritis |
| url | https://doi.org/10.1038/s41598-023-42324-6 |
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