Kanaya Minoru, Shibuya Kazuko, Hirochika Rei, Kanemoto Miyoko, Ohashi Kazuteru, Okada Masafumi, Wagatsuma Yukiko, Cho Yukiko, Kojima Hiroshi, Teshima Takanori, Imamura Masahiro, Sakamaki Hisashi, Shibuya Akira
Department of Immunology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
PLoS One. 2016 Jun 3;11(6):e0154173. doi: 10.1371/journal.pone.0154173. eCollection 2016.
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD.
急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）的主要并发症。由于aGVHD的诊断完全基于临床症状和病理表现，因此需要可靠且无创的实验室检测来进行准确诊断。一种激活型免疫受体DNAM-1（CD226）在T细胞和自然杀伤细胞上表达，并参与aGVHD的发生发展。在此，我们在人血清中鉴定出了一种可溶性形式的DNAM-1（sDNAM-1）。在对单中心的allo-HSCT患者（n = 71）进行的回顾性单因素和多因素分析中，在allo-HSCT前7天血清sDNAM-1最高水平较高（≥30 pM）的患者中，所有级别（I-IV级）和II-IV级aGVHD的累积发生率显著高于同期血清sDNAM-1最高水平较低（<30 pM）的患者。然而，sDNAM-1与其他已知的allo-HSCT并发症无关。我们的数据表明，sDNAM-1可能是aGVHD发生发展的一种独特的预测生物标志物候选物。
