Interleukin-2 (IL-2) is one of the most important cytokines that regulate the activation and proliferation of T cells and natural killer cells. The production of IL-2 may be affected by polymorphisms in the promoter region of the gene (rs2069762). In allogeneic hematopoietic cell transplantation (HCT) from adult donors, rs2069762 has been associated with the incidence of acute and chronic graft-versus-host disease (GVHD). However, the impacts of IL-2 polymorphism on cord blood transplantation (CBT) outcomes remain unclear. The objective of this study was to assess the impact of IL-2 polymorphism rs2069762 on transplant outcomes, such as hematopoietic recovery, GVHD, overall survival, relapse, and non-relapse mortality (NRM) after CBT. We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from November 2005 to March 2023 for whom DNA samples from recipients and donors were available. IL-2 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2069762. A total of 143 recipient and donor pairs were included in this study. The proportion of recipient IL-2 polymorphism rs2069762 was 48 % (n = 69) for AA, 42 % (n = 60) for CA, and 10 % (n = 14) for CC. The proportion of donor IL-2 polymorphism rs2069762 was 43 % (n = 61) for AA, 48 % (n = 69) for CA, and 9 % (n = 13) for CC. In the multivariate analysis, the use of an rs2069762 CA + CC donor was associated with lower neutrophil recovery compared to an rs2069762 AA donor (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.50–0.88; P = 0.004). Furthermore, recipients of rs2069762 CA + CC were associated with higher NRM compared to recipients of rs2069762 AA (HR, 2.32; 95 % CI, 1.01–5.34; P = 0.047). Serum IL-2 levels at 8 weeks were significantly higher in rs2069762 CA + CC recipients compared to those with rs2069762 AA recipients (P = 0.014). Our data showed that donor IL-2 polymorphism affects neutrophil recovery and recipient IL-2 polymorphism affects NRM in adults undergoing single-unit CBT. The polymorphism of IL-2 rs2069762 in recipients and donors might be associated with the clinical outcomes of single-unit CBT.

中文翻译：

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IL-2多态性rs2069762对单单位脐带血移植结局的影响


白细胞介素-2 (IL-2) 是调节 T 细胞和自然杀伤细胞活化和增殖的最重要的细胞因子之一。 IL-2 的产生可能受到该基因启动子区 (rs2069762) 多态性的影响。在成人捐献者的同种异体造血细胞移植 (HCT) 中，rs2069762 与急性和慢性移植物抗宿主病 (GVHD) 的发生率相关。然而，IL-2 多态性对脐带血移植（CBT）结果的影响仍不清楚。本研究的目的是评估 IL-2 多态性 rs2069762 对移植结果的影响，例如 CBT 后的造血恢复、GVHD、总生存率、复发和非复发死亡率 (NRM)。我们对 2005 年 11 月至 2023 年 3 月在我们机构接受单单位 CBT 的成年患者的数据进行了回顾性分析，这些患者的 DNA 样本来自接受者和捐赠者。使用实时聚合酶链反应和 TaqMan® SNP 基因分型测定对 rs2069762 进行 IL-2 基因分型。本研究共纳入 143 对受者和捐赠者。 AA 的受体 IL-2 多态性 rs2069762 的比例为 48% (n = 69)，CA 为 42% (n = 60)，CC 为 10% (n = 14)。供体 IL-2 多态性 rs2069762 的比例对于 AA 为 43% (n = 61)，对于 CA 为 48% (n = 69)，对于 CC 为 9% (n = 13)。在多变量分析中，与 rs2069762 AA 供体相比，使用 rs2069762 CA + CC 供体与中性粒细胞恢复较低相关（风险比 [HR]，0.66；95% 置信区间 [CI]，0.50–0.88；P = 0.004 ）。此外，与 rs2069762 AA 的接受者相比，rs2069762 CA + CC 的接受者与更高的 NRM 相关（HR，2.32；95% CI，1.01–5.34；P = 0.047）。 与 rs2069762 AA 受体相比，rs2069762 CA + CC 受体在第 8 周时的血清 IL-2 水平显着较高（P = 0.014）。我们的数据显示，供体 IL-2 多态性影响中性粒细胞恢复，受体 IL-2 多态性影响接受单单位 CBT 的成人的 NRM。受者和供者 IL-2 rs2069762 多态性可能与单单位 CBT 的临床结果相关。