Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
School of Medicine, University of Tsukuba, Tsukuba, Japan.
PLoS One. 2020 Feb 10;15(2):e0228508. doi: 10.1371/journal.pone.0228508. eCollection 2020.
DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD.
DNAM-1（CD226）是一种在 T 细胞和 NK 细胞上表达的激活型免疫受体，参与异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）的发病机制。我们之前报道过，DNAM-1 的可溶性形式（sDNAM-1）通过激活的 T 细胞脱落产生。此外，基于 allo-HSCT 患者的回顾性单变量和多变量分析，移植前患者血清中 sDNAM-1 水平较高是发生 aGVHD 的预测生物标志物。然而，sDNAM-1 血清水平在 allo-HSCT 后的调节方式以及它们是否与 aGVHD 的发生有关仍不清楚。在这里，我们构建了一个数学模型，通过假设存在三种类型的 sDNAM-1（第一种和第二种分别来自同种异体反应性和非同种异体反应性供体细胞淋巴细胞，第三种来自受体淋巴细胞），来评估 allo-HSCT 后 sDNAM-1 的动力学。我们的数学模型很好地拟合了接受 allo-HSCT 的患者（n=67）的 sDNAM-1 数据集，并表明第一种 sDNAM-1 与第一和第二种 sDNAM-1 总和的高比例与发生严重 aGVHD 的高风险相关。因此，allo-HSCT 后的 sDNAM-1 可以作为 aGVHD 发生的生物标志物。
