Association of HLA-class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population
Copyright © 2023 Kawasaki, Sada, Kusumawati, Hirano, Kobayashi, Nagasaka, Sugihara, Ono, Fujimoto, Kusaoi, Tamura, Kusanagi, Itoh, Sumida, Yamagata, Hashimoto, Makino, Arimura, Harigai and Tsuchiya..
Background: Disease relapse remains a major problem in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations, HLA-DPB1*04:01 is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association between HLA-DRB1*09:01 and DQB1*03:03 with susceptibility to, and DRB1*13:02 with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association of DQA1*03:02, which is in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whether HLA-class II is associated with the risk of relapse in MPO-AAV.
Methods: First, the association of HLA-DQA1*03:02 with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reported DRB1*09:01 and DQB1*03:03 were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (Puncorr) were corrected for multiple comparisons in each analysis using the false discovery rate method.
Results: The association of DQA1*03:02 with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: Puncorr=5.8x10-7, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40-2.16, MPA: Puncorr=1.1x10-5, OR 1.71, 95%CI 1.34-2.17). DQA1*03:02 was in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers of DRB1*09:01 (Puncorr=0.049, Q=0.42, hazard ratio [HR]:1.87), DQA1*03:02 (Puncorr=0.020, Q=0.22, HR:2.11) and DQB1*03:03 (Puncorr=0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DRβ1 (HLA-DRβ1_13S), including DRB1*13:02 carriers, showed longer relapse-free survival with nominal significance (Puncorr=0.010, Q=0.42, HR:0.31). By combining DQA1*03:02 and HLA-DRβ1_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (Puncorr=0.0055, Q=0.033, HR:4.02).
Conclusion: HLA-class II is associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 28., Seite 1119064 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kawasaki, Aya [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.03.2023 Date Revised 28.03.2023 published: Electronic-eCollection figshare: 10.6084/m9.figshare.21876159.v3 Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1119064 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354742825 |
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| 100 | 1 | |a Kawasaki, Aya |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association of HLA-class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 28.03.2023 | ||
| 500 | |a Date Revised 28.03.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a figshare: 10.6084/m9.figshare.21876159.v3 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Kawasaki, Sada, Kusumawati, Hirano, Kobayashi, Nagasaka, Sugihara, Ono, Fujimoto, Kusaoi, Tamura, Kusanagi, Itoh, Sumida, Yamagata, Hashimoto, Makino, Arimura, Harigai and Tsuchiya. | ||
| 520 | |a Background: Disease relapse remains a major problem in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations, HLA-DPB1*04:01 is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association between HLA-DRB1*09:01 and DQB1*03:03 with susceptibility to, and DRB1*13:02 with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association of DQA1*03:02, which is in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whether HLA-class II is associated with the risk of relapse in MPO-AAV | ||
| 520 | |a Methods: First, the association of HLA-DQA1*03:02 with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reported DRB1*09:01 and DQB1*03:03 were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (Puncorr) were corrected for multiple comparisons in each analysis using the false discovery rate method | ||
| 520 | |a Results: The association of DQA1*03:02 with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: Puncorr=5.8x10-7, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40-2.16, MPA: Puncorr=1.1x10-5, OR 1.71, 95%CI 1.34-2.17). DQA1*03:02 was in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers of DRB1*09:01 (Puncorr=0.049, Q=0.42, hazard ratio [HR]:1.87), DQA1*03:02 (Puncorr=0.020, Q=0.22, HR:2.11) and DQB1*03:03 (Puncorr=0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DRβ1 (HLA-DRβ1_13S), including DRB1*13:02 carriers, showed longer relapse-free survival with nominal significance (Puncorr=0.010, Q=0.42, HR:0.31). By combining DQA1*03:02 and HLA-DRβ1_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (Puncorr=0.0055, Q=0.033, HR:4.02) | ||
| 520 | |a Conclusion: HLA-class II is associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ANCA-associated vasculitis (AAV) | |
| 650 | 4 | |a HLA-class II | |
| 650 | 4 | |a MPO-ANCA | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a microscopic polyangiitis (MPA) | |
| 650 | 4 | |a polymorphism | |
| 650 | 4 | |a relapse | |
| 650 | 7 | |a Antibodies, Antineutrophil Cytoplasmic |2 NLM | |
| 650 | 7 | |a Peroxidase |2 NLM | |
| 650 | 7 | |a EC 1.11.1.7 |2 NLM | |
| 650 | 7 | |a Myeloblastin |2 NLM | |
| 650 | 7 | |a EC 3.4.21.76 |2 NLM | |
| 700 | 1 | |a Sada, Ken-Ei |e verfasserin |4 aut | |
| 700 | 1 | |a Kusumawati, Premita Ari |e verfasserin |4 aut | |
| 700 | 1 | |a Hirano, Fumio |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Shigeto |e verfasserin |4 aut | |
| 700 | 1 | |a Nagasaka, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Sugihara, Takahiko |e verfasserin |4 aut | |
| 700 | 1 | |a Ono, Nobuyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Fujimoto, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Kusaoi, Makio |e verfasserin |4 aut | |
| 700 | 1 | |a Tamura, Naoto |e verfasserin |4 aut | |
| 700 | 1 | |a Kusanagi, Yasuyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Itoh, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Sumida, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Yamagata, Kunihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Hashimoto, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Makino, Hirofumi |e verfasserin |4 aut | |
| 700 | 1 | |a Arimura, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Harigai, Masayoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuchiya, Naoyuki |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2023.1119064 |3 Volltext |
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