HLA-DP 表达在异基因供体移植后移植物抗宿主病中的作用。
Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation.
机构信息
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA.
出版信息
J Clin Oncol. 2020 Aug 20;38(24):2712-2718. doi: 10.1200/JCO.20.00265. Epub 2020 Jun 1.
PURPOSE
The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors.
PATIENTS AND METHODS
Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients.
RESULTS
In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; = .001) and severe acute GVHD (OR, 1.32; = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype.
CONCLUSION
The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.
目的
本研究的主要目的是评估 HLA-A、-B、-C、-DRB1、-DQB1 匹配和不匹配的无关供者造血细胞移植（HCT）后 HLA-DPB1 表达在急性移植物抗宿主病（GVHD）中的意义。
患者和方法
在 1988 年至 2016 年间，澳大利亚、欧盟、日本、北美和英国进行了 HLA-A、-B、-C、-DRB1、-DQB1 匹配或不匹配的无关供者 HCT，我们评估了 19136 例接受 HCT 的患者。在 HLA-DPB1 单一位点错配的移植受者中，患者错配的 HLA-DPB1 同种异型被定义为低表达或高表达。多变量回归模型用于评估与 HLA-DPB1 错配相关的高表达与低表达相比，GVHD 的风险。在 HLA 错配移植受者中，评估了 HLA-DPB1 错配数量增加对临床结果的影响。
结果
在 HLA-A、-B、-C、-DRB1、-DQB1 匹配的移植受者中，与患者 HLA-DPB1 高表达错配相比，供体对一个高表达患者 HLA-DPB1 的错配增加了中度（比值比 [OR]，1.36；.001）和严重急性 GVHD（OR，1.32；.0016），而与低表达患者错配无关，无论供体 HLA-DPB1 错配的表达水平如何。在 HLA-A、-B、-C、-DRB1 或-DQB1 错配的移植受者中，随着 HLA-DPB1 错配数量的增加，急性 GVHD 的几率增加（中度 GVHD 的 OR 为 1.23，OR 为 1.40；对于零错配；严重 GVHD 的 OR 为 1.19，OR 为 1.40；对于零错配），但与患者错配 HLA-DPB1 同种异型的表达水平无关。
结论
患者 HLA-DPB1 错配的表达水平提示 HLA-A、-B、-C、-DRB1、-DQB1 匹配无关 HCT 后发生 GVHD 的风险，HLA-DPB1 错配的总数提示 HLA 错配无关 HCT 后发生 GVHD 的风险。前瞻性考虑 HLA-DPB1 可能有助于降低移植后的 GVHD 风险。
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