Soluble NKG2D Ligands Are Potential Biomarkers and Sentinels of Immune-Mediated Bone Marrow Injury in Bone Marrow Failure Syndromes.
Soluble NKG2D Ligands Are Potential Biomarkers and Sentinels of Immune-Mediated Bone Marrow Injury in Bone Marrow Failure Syndromes.
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可溶性 NKG2D 配体是骨髓衰竭综合征中免疫介导的骨髓损伤的潜在生物标志物和哨兵。
DOI：
10.1159/000500657
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Hanaoka N.
中科院分区：
文献类型：
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作者：
Murata S;Mushino T;Hosoi H;Kuriyama K;Nishikawa A;Nagakura S;Horikawa K;Yonemura Y;Nakakuma H;Sonoki T;Hanaoka N.
免疫介导的过程被认为在骨髓衰竭综合征（BFS）的发病机制中很重要。我们先前报道了自然杀伤组2D（NKG2D）配体在BFS患者的病理血细胞上表达，并且NKG2D免疫可能参与骨髓衰竭。除细胞表面的膜NKG2D配体外，可溶性NKG2D配体可存在于血浆中。因此，我们研究了86例BFS患者可溶性NKG2D配体与血细胞计数之间的关系，包括再生障碍性贫血、骨髓增生异常综合征伴单系发育不良和阵发性睡眠性血红蛋白尿症。通过酶联免疫吸附试验，大约一半的BFS患者血浆中可溶性NKG2D配体呈阳性，可溶性NKG2D配体阳性的BFS患者表现出重度血细胞减少，无论膜NKG2D配体表达如何。体外分析表明，可溶性ULBP1（一种NKG2D配体）下调外周血中CD2阳性细胞上的NKG2D受体。此外，可溶性ULBP1减弱了外周血单核细胞对表达膜ULBP1的K562的细胞毒性作用。我们的研究结果表明，可溶性NKG2D配体可以是易于测量的生物标志物，用于预测BFS中免疫介导的骨髓损伤的活性，并且可溶性NKG2D配体抑制多余的免疫介导的骨髓损伤。
Immune-mediated processes are considered important in the pathogenesis of bone marrow failure syndromes (BFS). We previously reported that natural killer group 2D (NKG2D) ligands were expressed on pathological blood cells of patients with BFS and that NKG2D immunity may be involved in bone marrow failure. In addition to membranous NKG2D ligands on the cell surface, soluble NKG2D ligands can exist in plasma. We therefore examined the relationship between soluble NKG2D ligands and blood cell counts in 86 patients with BFS, including aplastic anemia, myelodysplastic syndrome with single lineage dysplasia, and paroxysmal nocturnal hemoglobinuria. Approximately half of the BFS patients were positive for soluble NKG2D ligands in the plasma by enzyme-linked immunosorbent assay, and soluble NKG2D ligand-positive BFS patients exhibited severe cytopenia regardless of membranous NKG2D ligand expression. In vitroanalyses demonstrated that soluble ULBP1, an NKG2D ligand, down-regulated NKG2D receptors on CD2-positive cells in peripheral blood. Moreover, soluble ULBP1 attenuated the cytotoxic effects of peripheral blood mononuclear cells on K562, which express membranous ULBP1. Our results suggest that soluble NKG2D ligands can be easy-to-measure biomarkers for the prediction of activity of immune-meditated bone marrow injury in BFS and that soluble NKG2D ligands suppress redundant immune-mediated bone marrow injury.