人外周血NK细胞及NKT细胞受体及亚群的差异表达与类风湿关节炎的关系

Changes of expression levels of NK,NKT cells and their receptors in peripheral blood of human and its correlation with rheumatoid arthritis

目的:探讨初诊类风湿关节炎(RA)患者的外周血NK和NKT细胞的活化性、抑制性受体及亚群表达水平的变化,揭示其在RA发病中的可能机制。方法:检测32例初诊RA患者和15例健康人的外周血NK和NKT细胞及其活化性受体和抑制性受体,对自发和刺激后的NK、NKT细胞分泌的IFN-γ、NKT细胞和CD107a+NK细胞进行检测,分析各细胞亚群与临床指标之间的潜在关系。结果:与健康对照组相比,初诊RA患者的NK细胞的比例显著降低(P=0.026);RA患者NK细胞活化性受体NKG2D+,NKP46+和NKT细胞活化性受体NKG2C+,NKG2D+,NKP46+的比例显著增高(P=0.011,P=0.010,P<0.001,P=0.032,P=0.001);NK细胞抑制性受体KIR2DL3+、KIR3DL1+和NKG2A+和NKT细胞抑制性受体KIR2DL3+,NKG2A+的比例显著降低(P=0.002,P=0.002,P=0.014,P=0.027,P=0.002);刺激后的IFN-γ+NK和IFN-γ+NKT细胞的比例,自发和刺激后的CD107a+NK细胞的比例在RA患者中要显著高于对照组(P=0.037,P=0.004,P=0.001,P=0.001)。此外,NK细胞、抑制性NK细胞受体NKG2A+和KIR2DL3+的比例和初诊RA患者的DAS28值显著相关(r=0.357,P=0.045;r=0.399,P=0.024;r=0.468,P=0.021)。结论:人外周血NK细胞及NKT细胞受体及亚群的差异表达、细胞功能的变化可能诱发RA的自身免疫反应。

Objective：To explore the changes of NK and NKT cells and the expression levels of their activated, inhibitory receptors in the peripheral blood of patients with newly diagnosed rheumatoid arthritis （ RA）, and to reveal the potiential role of NK and NKT cells played in the pathogenesis of RA.Methods：32 patients with new onset RA and 15 healthy controls were recruited.Activated and inhibitory NK and NKT cells in peripheral blood were quantified by flow cytometry.The frequency of spontaneous and stimulated IFN-γ＋NK and NKT cells and CD107aγ＋NK cells were examined.Finally,the potential relationship between the frequency of NK and NKT cells subsets and clinical indexes were analyzed.Results：The frequencies of NK cells in peripheral blood in RA patients were sig-nificantly lower than those in the controls （ P=0.026 ）.The frequencies of NKG2D＋, NKP46＋activated NK cells and NKG2C＋, NKG2D＋,NKP46＋activated NKT cells in RA patients were significantly higher than those in the controls （P=0.011,P=0.010,and P＆lt;0.001,P=0.032,P=0.001,respectively）,whereas the frequencies of KIR2DL3＋,KIR3DL1＋and NKG2A＋inhibitory NK cells and KIR2DL3＋,NKG2A＋inhibitory NKT cells in RA patients were significantly lower （P=0.002,P=0.002,P=0.014,and P=0.027,P=0.002,respectively）.Moreover, the frequencies of stimulated IFN-γ＋NK cells and IFN-γ＋NKT cells, spontaneous and stimulated CD107 aγ＋NK cells in RA patients were significantly higher than that in the controls （ P=0.037, P=0.004 and P=0.001, P=0.001, respectively）.Furthermore,the frequencies of NK cells,NKG2Aγ＋and KIR2DL3γ＋inhibitory NK cells were correlated significantly with the values of DAS28 in RA patients （r=0.357,P=0.045;r=0.399,P=0.024;r=0.468,P=0.021,respectively）.Conclusion：Lower frequencies of NK cells, higher frequencies of activated NK cells and activated NKT cells, lower frequencies of inhibitory NK cells and inhibitory NKT cells, and higher NK cell activity may induce the autoimmune reaction involved in the pathogenesis of RA.