CAJ | 학술논문

目的探讨多发性骨髓瘤(MM)患者NK细胞杀伤功能下降的机制.方法以13例MM患者为研究对象,以30名健康志愿者为正常对照,采用流式细胞术检测外周血单个核细胞中CD3-CD56+ (NK细胞)表面抑制性受体(CD158a和CD158b)以及活化性受体NKG2D、NCRs (NKp30、NKp44、NKp46)的表达水平;ELISA法检测血清可溶性NKG2D配体水平;流式细胞术检测NK细胞对MM细胞株U266细胞杀伤作用的变化.结果 MM患者外周血中NK细胞比例及绝对数、CD158a和CD 158b表达水平与对照组比较差异无统计学意义(P值均＞0.05),两组NK细胞表面均不表达NKp44;与对照组比较,MM患者NK细胞表面活化性受体(NKG2D、NKp30和NKp46)水平均明显降低,血清中可溶性NKG2D配体水平明显升高,差异均有统计学意义(P值均＜0.05);用MM患者血清培养后的正常对照者NK细胞对U266细胞的杀伤能力较共培养前明显下降[(25.4±5.9)％对(38.5±6.5)％],差异有统计学意义(P=0.044).结论 MM患者血清可溶性NKG2D配体水平可能是导致NK细胞杀伤活性下降的原因.
목적 탐토다발성골수류(MM)환자NK세포살상공능하강적궤제.방법 이13례MM환자위연구대상,이30명건강지원자위정상대조,채용류식세포술검측외주혈단개핵세포중CD3-CD56+ (NK세포)표면억제성수체(CD158a화CD158b)이급활화성수체NKG2D、NCRs (NKp30、NKp44、NKp46)적표체수평;ELISA법검측혈청가용성NKG2D배체수평;류식세포술검측NK세포대MM세포주U266세포살상작용적변화.결과 MM환자외주혈중NK세포비례급절대수、CD158a화CD 158b표체수평여대조조비교차이무통계학의의(P치균＞0.05),량조NK세포표면균불표체NKp44;여대조조비교,MM환자NK세포표면활화성수체(NKG2D、NKp30화NKp46)수평균명현강저,혈청중가용성NKG2D배체수평명현승고,차이균유통계학의의(P치균＜0.05);용MM환자혈청배양후적정상대조자NK세포대U266세포적살상능력교공배양전명현하강[(25.4±5.9)％대(38.5±6.5)％],차이유통계학의의(P=0.044).결론 MM환자혈청가용성NKG2D배체수평가능시도치NK세포살상활성하강적원인.
Objective To explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).Methods The expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30,NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry.The concentration of soluble NKG2D ligands (MICA,MICB,ULBP 1,ULBP2 and ULBP3) in serum was detected by enzyme-linked immunosorbent assay (ELISA),and the cytotoxicity of NK cell against MM cell line by flow cytometry.Results There are no significant differences of percentage and absolute number of NK cells,and the expression level of CD 158a and CD 158b between MM patients and healthy individuals (P＞0.05).No NKp44 expression was detected on fresh isolated NK cells from both groups.There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D,NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals.The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P＜0.05).Cultured healthy individual' s NK cells with MM patient' s serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5±6.5)％ vs (25.4±5.9)％,P=0.044].Conclusion The higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.