The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation
The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation
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DOI：
10.1007/s12032-015-0664-1
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发表时间：
2015-08-01
期刊：
影响因子：
3.4
通讯作者：
Kuliczkowski, Kazimierz
中科院分区：
文献类型：
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作者：
Biedron, Monika;Rybka, Justyna;Kuliczkowski, Kazimierz
HLA-G是一种非经典的MHC I类分子，其对免疫效应细胞的抑制活性是由于与受体ILT 2、ILT 4和KIR 2DL 4的相互作用而发挥的。这些受体主要在NK细胞和单核细胞上表达，并且其表达强度根据HLA-G水平而变化。HLA-G在器官移植和骨髓干细胞移植后耐受的发展中起重要作用。HLA-G还参与癌发生期间免疫应答的调节。本研究旨在探讨异基因造血干细胞移植患者血清HLA-G水平、NK细胞和单核细胞表达HLA-G受体（ILT 2、ILT 4、KIR 2DL 4和NKG 2D）的百分比及其对移植物抗宿主反应发生的影响。该研究包括32例接受异基因干细胞移植的骨髓疾病患者（急性白血病，骨髓增生异常综合征，慢性髓细胞白血病，阵发性睡眠性血红蛋白尿症）。我们评估了患者预处理前、异基因骨髓干细胞移植后移植造血重建期单核细胞和NK细胞上ILT 2、ILT 4、KIR 2DL 4和NKG 2D受体的表达以及血清中HLA-G水平。0 ~ I级GVHD患者NK细胞表达KIR 2DL 4、ILT 2和ILT 4受体的百分比高于II ~ IV级GVHD患者。0-I级GVHD患者ILT 4和ILT 2受体表达的单核细胞百分比高于II-IV级GVHD患者。造血干细胞移植后患者血清HLA-G水平较移植前升高。HLA-G水平和HLA-G受体与GVHD的严重程度有关，并可能在GVHD的发生和临床进程中发挥预后因素的作用。
HLA-G is a non-classical MHC class I molecule whose suppressive activity on immune effector cells is exerted due to interactions with receptors ILT2, ILT4 and KIR2DL4. These receptors are expressed mainly on NK cells and monocytes, and their intensity of expression changes depending on HLA-G level. HLA-G plays an important role in the development of tolerance following organ transplantations and bone marrow stem cell transplantations. HLA-G also participates in the modulation of the immune response during cancerogenesis. The aim of this study was to assess HLA-G level in blood serum, the percentage of NK cells and monocytes with expression of receptors for HLA-G (ILT2, ILT4, KIR2DL4 and NKG2D) in patients who received allogeneic stem cell transplantations, and their influence on the occurrence of graft-versus-host reaction. The study included 32 patients with bone marrow diseases (acute leukemias, myelodysplastic syndrome, chronic myeloid leukemia, paroxysmal nocturnal hemoglobinuria) who received allogeneic stem cell transplantations. We assessed the expression of receptors ILT2, ILT4, KIR2DL4 and NKG2D on monocytes and NK cells, as well as the level of HLA-G in blood serum in patients before conditioning, in the transplant hematopoietic reconstitution period following allogeneic bone marrow stem cell transplantation. The percentage of NK cells with expression of KIR2DL4, ILT2 and ILT4 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The percentage of monocytes with expression of ILT4 and ILT2 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The level of HLA-G in patients' blood serum was higher after the stem cell transplantation compared with the period before transplantation. HLA-G level and HLA-G receptors are related to intensity of GVHD and may play the role of a prognostic factor for the development of GVHD and the clinical course of this reaction.