Sequence Variations Within HLA-G and HLA-F Genomic Segments at the Human Leukocyte Antigen Telomeric End Associated With Acute Graft-Versus-Host Disease in Unrelated Bone Marrow Transplantation.
Sequence Variations Within HLA-G and HLA-F Genomic Segments at the Human Leukocyte Antigen Telomeric End Associated With Acute Graft-Versus-Host Disease in Unrelated Bone Marrow Transplantation.
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DOI：
10.3389/fimmu.2022.938206
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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急性移植物抗宿主病（Acute graft-versus-host disease，aGVHD）是指异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，HCT）后早期发生的移植物对宿主的免疫反应综合征。即使在与多个基因位点的人类白细胞抗原（HLA）等位基因匹配的HCT中也经常观察到这种疾病。虽然HLA区域代表复杂多样的基因组特征，但需要详细的关联分析来鉴定与aGVHD强烈相关的未表征变体。我们对位于460 kb HLA端粒区的三个位点（OR 2 H2、HLA-F-AS 1和HLA-G）进行基因分型，并对包括HLA-DPB 1在内的基因型与临床和移植结果进行统计学分析，使用338对HLA-A、HLA-B、HLA-C、HLA-DRB 1和HLA-DQB 1（HLA-10/10）匹配的无关骨髓移植（UR-BMT）患者-供体对。多变量分析表明，HLA-F-AS 1和HLA-DPB 1错配与II-IV级aGVHD相关（风险比（HR），1.76; 95% CI，1.07-2.88; p = 0.026; HR，1.59; CI，1.02-2.49; p = 0.042）。在HLA-F-AS 1和HLA-DPB 1之间没有混杂（p = 0.512），表明HLA-F-AS 1错配对aGVHD具有独立于HLA-DPB 1的强烈影响。此外，分层分析表明HLA-F-AS 1、HLA-DPB 1和/或HLA-G错配与II-IV级aGVHD和更严重的III-IV级aGVHD可能相关。这些发现为理解HLA匹配的UR-BMT引起aGVHD的分子机制提供了新的见解。
Acute graft-versus-host disease (aGVHD) is defined as a syndrome of an immunological response of graft to the host that occurs early after allogeneic hematopoietic stem cell transplantation (HCT). This disease is frequently observed even in HCT matched for human leukocyte antigen (HLA) alleles at multiple gene loci. Although the HLA region represents complex and diverse genomic characteristics, detailed association analysis is required for the identification of uncharacterized variants that are strongly associated with aGVHD. We genotyped three loci, OR2H2, HLA-F-AS1, and HLA-G, that are located in the 460 kb of HLA telomeric region and statistically analyzed the genotypes including HLA-DPB1 with clinical and transplantation outcomes using 338 unrelated bone marrow transplantation (UR-BMT) patient–donor pairs who were matched for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 (HLA-10/10). Multivariate analyses demonstrated that HLA-F-AS1 and HLA-DPB1 mismatches were associated with grade II–IV aGVHD (hazard ratio (HR), 1.76; 95% CI, 1.07–2.88; p = 0.026; and HR, 1.59; CI, 1.02–2.49; p = 0.042, respectively). There was no confounding between HLA-F-AS1 and HLA-DPB1 (p = 0.512), suggesting that the HLA-F-AS1 mismatch has a strong effect on aGVHD independently of HLA-DPB1. Moreover, a stratified analysis suggested possible associations of HLA-F-AS1, HLA-DPB1, and/or HLA-G mismatches with grade II–IV aGVHD and the more severe grade III–IV aGVHD. These findings provide new insights into understanding the molecular mechanism of aGVHD caused by HLA-matched UR-BMT.
影响因子：
7.3
作者：
Suzuki S;Ranade S;Osaki K;Ito S;Shigenari A;Ohnuki Y;Oka A;Masuya A;Harting J;Baybayan P;Kitazume M;Sunaga J;Morishima S;Morishima Y;Inoko H;Kulski JK;Shiina T
通讯作者：
Shiina T