Department of Hematology and Oncology, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Sci Rep. 2020 Dec 3;10(1):21150. doi: 10.1038/s41598-020-78259-5.
Viral infection is more frequently reported in cord blood transplantation (CBT) than in transplantation of other stem cell sources, but its precise mechanism related to antiviral host defenses has not been elucidated yet. To evaluate the effect of human leukocyte antigen (HLA) class I allele-level incompatibility on viral infection in CBT, we conducted a single-center retrospective study. Total 94 patients were included, and viral infections were detected in 32 patients (34%) within 100 days after CBT. HLA-C mismatches in graft-versus-host direction showed a significantly higher incidence of viral infection (hazard ratio (HR), 3.67; p = 0.01), while mismatches in HLA-A, -B, or -DRB1 were not significant. Overall HLA class I mismatch was also a significant risk factor and the predictor of post-CBT viral infection (≥ 3 mismatches, HR 2.38, p = 0.02), probably due to the insufficient cytotoxic T cell recognition and dendritic cell priming. Patients with viral infection had significantly worse overall survival (52.7% vs. 72.1%; p = 0.02), and higher non-relapse mortality (29.3% vs. 9.8%; p = 0.01) at 5 years. Our findings suggest that appropriate graft selection as well as prophylaxis and early intervention for viral infection in such high-risk patients with ≥ 3 HLA class I allele-level mismatches, including HLA-C, may improve CBT outcomes.
病毒感染在脐带血移植(CBT)中比其他干细胞来源的移植更为常见,但与抗病毒宿主防御相关的确切机制尚未阐明。为了评估人类白细胞抗原(HLA)I 类等位基因水平不相容对 CBT 中病毒感染的影响,我们进行了一项单中心回顾性研究。共纳入 94 例患者,在 CBT 后 100 天内,32 例(34%)患者检测到病毒感染。移植物抗宿主方向的 HLA-C 错配显示出更高的病毒感染发生率(风险比(HR),3.67;p=0.01),而 HLA-A、-B 或-DRB1 的错配则不显著。总体 HLA I 类错配也是 CBT 后病毒感染的显著危险因素和预测因子(≥3 个错配,HR 2.38,p=0.02),可能是由于细胞毒性 T 细胞识别和树突状细胞启动不足。发生病毒感染的患者总体生存率明显较差(52.7% vs. 72.1%;p=0.02),5 年非复发死亡率也更高(29.3% vs. 9.8%;p=0.01)。我们的研究结果表明,对于具有≥3 个 HLA I 类等位基因水平错配(包括 HLA-C)的高危患者,适当的移植物选择以及对病毒感染的预防和早期干预,可能会改善 CBT 结局。