乙型肝炎患者NK细胞亚群的变化

Study the change of NK cells phenotype in acute and the various periods of chronic HBV infection

目的 探讨固有免疫反应中自然杀伤（natural killer,NK）细胞在正常人群、急性及慢性HBV感染各个时期的变化.方法 采集17例急性乙型肝炎（acute hepatitis B,AHB）、24例慢性HBV感染免疫耐受期（immune tolerance phase,IT）、15例慢乙肝免疫清除期（immune clearance phase,IC）和12例健康成人（healthy individuals,HI）的静脉全血.检测外周血NK细胞频数、CD56^brightNK亚群、CD56dimNK、NKp46high、NK表面活化性受体NKG2D之一（NKp46）在AHB、IC、IT、HI的表达,并分析其与临床转归的关系.结果 NK细胞频数在AHB（9.84±5.34％）和IC组（10.17±6.23％）较HI（14.32 ±4.82％）和IT组（17.47±8.14％）显著减少（AHB vs ITP=0.001;IC vs IT,P=0.002;ABH vs HIP=0.025;IC vsHIP=0.035;）.CD56^bright NK亚群在HI（5.09±3.03％）和IT组（3.51±2.13％）较AHB（6.99±5.27％）和IC组（8.41±6.15％）降低,且IT组降低更显著（P分别为0.007,0.001）.CD^56dimNK细胞在IT组（96.78±7.24％）较HI（91.71±3.28％）、AHB（92.08±5.65％）和IC组（90.98±6.27％）显著升高（P =0.024,P=0.017,P=0.004）.NKp46^highNK细胞在IT组（7.9±7.26）较AHB（12.79±8.42）和IC组（11.78±4.76）降低（P =0.019,P=0.008）.结论 HBV感染患者NK细胞频数、CD56^brightNK亚群、CD56dimNK亚群及NKp46highNK亚群分布方面,AHB和IC患者均与IT期患者差异有统计学意义,在AHB和IC患者间并无显著差异.HI与IT在NK细胞频数、CD56brightNK亚群及NKp46highNK亚群分布方面差异无统计学意义.这种IC期、AHB与IT期NK细胞频数与亚群的不同变化,支持HBV感染后临床抗病毒时期的选择.

Objective This study aimed atevaluating the difference of natural killer（NK） cells in the normal population,the patients with acute and chronic HBV infection.Methods Venous whole blood samples were obtained from 12 cases of healthy adults （HI） and a cohort of patients：17 cases of acute hepatitis B （AHB）,patients with chronic HBV infection including 24 cases of immune tolerance period （IT）,15 cases of immune clearance phase （IC）.Detect the frequency of peripheral blood NK and its phenotype like CD56brightNK,CD56dim NK,NKp46high NK,the expression of NKp46 （one of the activated receptor NKG2D） in the AHB,IC,IT,HIby flow cytometry.And then analyze its relationship with the clinical outcome.Results The results of variance analysis on the experimental data were as follows：the frequency of NK cells was significantly reduced in the AHB group （9.84 ±5.34%） and IC （10.17 ±6.23%） than the HI （14.32 ±4.82%） and the IT group （17.47 ± 8.14%）,（AHB vs IT,P =0.001;IC vs IT,P =0.002;P =0.025 ABH vs HI;IC vs HI P =0.035）.CD56brightNK phenotype in HI group （5.09 ± 3.03%） and IT （3.51 ±2.13%） decreased than the AHB group （6.99 ±5.27%） and IC （8.41 ±6.15%）,and the IT group was reduced more significantly （P =0.007,P =0.001）.CD56dimNK cells in the IT group （96.78 ± 7.24%）were significantly increased than the HI group（91.71 ± 3.28%）,the AHB group （92.08 ± 5.65%） and the IC group （90.98 ±6.27%） （P =0.024,P =0.024,P =0.004）.NKp46highNK cells in the IT group （7.9±7.26） decreased than the AHB（12.79 ±8.42and the IC group（11.78 ±4.76）（P=0.019,P =0.019）.Conclusions In the respect of the frequency of NK cells and the distribution of CD56brightNK subgroup,CD56dimNK phenotype and NKp46high NK subsets in patients with HBV infection,the difference between AHB,IC patients and IT patients were statistically significant.No significant differences were found between AHB and IC patients.HI and IT in the frequency of NK cells.And the distribution of CD56brightNK subgroup and NKp46high NK subsets had the differences of no statistical significance.Theses changes of the frequency of NK cells and the different phenotype in IC,AHB and IT,support the choice of clinical antiviral period after HBV infection.