多种血液肿瘤中NK细胞受体表达差异的临床意义

Clinical significance of differences in NK cell receptor expression in various hematological malignancies

目的:检测几种血液肿瘤患者中自然杀伤(NK)细胞受体变化,以探究NK细胞功能状态。方法:收集多发性骨髓瘤(MM)患者38例,其中IgG-k型18例、IgG-λ型10例、IgA-k型4例、IgA-λ型6例;非霍奇金淋巴瘤(NHL)患者27例,其中弥漫性大B细胞淋巴瘤18例、边缘区淋巴瘤3例、滤泡性淋巴瘤1例、套细胞淋巴瘤2例、免疫母性T细胞淋巴瘤1例、外周T细胞淋巴瘤2例;慢性髓系细胞白血病(CML)患者10例;30例健康志愿者为正常对照组。通过流式细胞术测定外周血中NK细胞占有核细胞比例,用实时荧光定量聚合酶链反应(RT-qPCR)方法检测NK细胞表面抑制性受体(PD-1)及活化性受体(CD69、NKG2D)的基因表达水平。结果:与正常对照组比较,MM、NHL患者外周血NK细胞占有核细胞比例比较,差异无统计学意义(P均>0.05);而CML患者NK细胞占有核细胞数显著减少(P<0.05);MM、NHL及CML患者的NK细胞表面活化性受体(CD69、NKG2D)水平较正常对照组明显降低,NK细胞表面抑制性受体(PD-1)表达显著高于正常对照组(P均<0.05);MM、NHL及CML患者间受体(PD-1、CD69、NKG2D)表达比较,差异无统计学意义(P均>0.05)。结论:MM、NHL及CML患者外周血NK细胞表面活化性受体(CD69、NKG2D)水平明显降低,抑制性受体(如PD-1)表达明显增高,提示NK细胞功能耗竭。

Objective:Natural killer(NK)cell receptor changes in patients with several hematological malignancies were examined to explore the functional status of NK cells.Methods:The peripheral blood samples of 38 patients with multiple myeloma(MM)were collected.There were 18 cases of IgG/(k),10 cases of IgG/(lambda),4 cases of IgA/(k),and 6 cases of IgA/(lambda).There were 27 cases of non-Hodgkin's lymphoma(NHL),including 18 cases of diffuse large B cell lymphoma,3 cases of marginal zone lymphoma,one case of follicular lymphoma,2 cases of mantle cell lymphoma,one case of angi-immmunoblastic T cell lymphoma,2 cases of peripheral T-cell lymphoma and 10 cases of chronic myeloid cell leukemia(CML).A total of 30 healthy volunteers served as the control group.The proportion of NK cells in the peripheral blood was determined using flow cytometry,and the proportion of surface inhibitory receptor(PD-1)and activated receptors(CD69,NKG2D)in NK cells were analyzed by RT-qPCR.Results:There was no significant difference in the proportion of NK cells in peripheral blood to nuclear cells between study group(MM patients and NHL patients)and normal controls(P>0.05),but the proportion of NK cells to nuclear cells decreased in CML patients(P<0.05).The levels of NK cell surface activation receptor(CD69 and NKG2D)were significantly reduced in MM,NHL,and CML patients as compared with normal controls(P<0.05).The NK cell surface inhibitory receptor(PD-1)expression was significantly higher in MM,NHL and CML patients than in normal controls(P<0.05).No significant difference was seen in the expression of receptors(CD69,NKG2D and PD-1)among MM,NHL and CML(P>0.05).Conclusion:The surface activated receptors(CD69 and NKG2D)in peripheral blood NK cells of MM,NHL and CML patients were significantly decreased,and the high expression of inhibitory receptor(PD-1)in MM,NHL and CML patients suggests the functional depletion.