Recipient PTPN22-1123 C/C Genotype Predicts Acute Graft-versus-Host Disease after HLA Fully Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies
Recipient PTPN22-1123 C/C Genotype Predicts Acute Graft-versus-Host Disease after HLA Fully Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies
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DOI：
10.1016/j.bbmt.2012.09.014
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发表时间：
2013-02-01
影响因子：
4.3
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
--
作者：
Espinoza, J. Luis;Takami, Akiyoshi;Nakao, Shinji
PTPN 22是T细胞应答的关键负调节因子。其启动子基因变异（rs 2488457，-1123 G>C）与自身免疫性疾病相关。本研究分析了PTPN 22变异体对663例患者移植结果的影响，这些患者通过日本骨髓捐献者计划接受了非相关HLA匹配的骨髓移植（BMT）治疗恶性血液病。受体C/C基因型与受体GIG基因型相比，导致II-IV级急性移植物抗宿主病的发生率较低（风险比[HR]，0.50; 95%置信区间[Cl]，0.29-0.85; P = .01），以及较高的复发率（HR，1.78; 95% CI，1.10-2.90; P = 0.02），如多变量分析所示。在高风险疾病患者中，受体C/C基因型与受体GIG基因型相比，总体生存率显著更差（HR，1.60; 95%CI，1.02-2.51; P = 0.04），而在标准风险疾病患者中，这种效应不存在。此外，供体G/C基因型与较低的复发率相关（HR，0.58; 95%CI，0.40-0.85），这并不影响生存率。我们的研究结果表明，PTPN 22基因分型可能有助于预测骨髓移植的预后，并为改善同种异体BMT的最终结局制定治疗策略。(C)2013年美国血液和骨髓移植协会。
PTPN22 is a critical negative regulator of T cell responses. Its promoter gene variant (rs2488457, -1123G>C) has been reported to be associated with autoimmune diseases. This study analyzed the impact of the PTPN22 variant on transplantation outcomes in a cohort of 663 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The recipient C/C genotype versus the recipient GIG genotype resulted in a lower incidence of grade II-IV acute graft-versus-host disease (hazard ratio [HR], 0.50; 95% confidence interval [Cl], 0.29-0.85; P = .01), as well as a higher incidence of relapse (HR, 1.78; 95% CI, 1.10-2.90; P = .02), as demonstrated on multivariate analysis. In patients with high-risk disease, the recipient C/C genotype was associated with significantly worse overall survival rates than the recipient GIG genotype (HR, 1.60; 95% Cl, 1.02-2.51; P = .04), whereas this effect was absent in patients with standard-risk disease. In addition, the donor G/C genotype was associated with a lower incidence of relapse (HR, 0.58; 95% CI, 0.40-0.85), which did not influence survival. Our findings suggest that PTPN22 genotyping could be useful in predicting prognoses and creating therapeutic strategies for improving the final outcomes of allogeneic BMT. (C) 2013 American Society for Blood and Marrow Transplantation.