急性和慢性乙型病毒性肝炎中自然杀伤细胞的功能研究

Natural killer cells function in acute and chronic hepatitis B patients

目的 探讨自然杀伤细胞（natural killer cells,NK）在慢性乙型病毒性肝炎（chronic hepatitis B,CHB）免疫活动期（immune active phase,IA）和急性乙型病毒性肝炎（acute hepatitis B,AHB）频数及功能的差异.方法 入组慢性乙型病毒性肝炎免疫活动期患者和急性乙型病毒性肝炎患者,分别在慢乙肝免疫活动期、急乙肝肝炎期和急乙肝恢复期检测其外周血NK细胞、CD56dim NK细胞、CD56bright NK细胞、IFNAR2＋ NK细胞、NKp46high NK细胞和NKp46dim NK细胞频数以及NK细胞表面功能分子IFNAR2、NKp46的表达情况,并分析它们与ALT、HBV DNA以及HBV markers相关性.结果 在IA和AHB两组间,AHB组NK细胞总频数、NKp46dim NK细胞频数显著低于IA组,但AHB组NKp46high NK细胞频数高于IA组.对于20例急乙肝恢复的患者,恢复期NK细胞和NKp46dim NK细胞频数显著高于急性炎症期,NKp46high NK细胞频数显著低于急性炎症期,而在急乙肝恢复前后CD56bright NK细胞频数和IFNAR2MFI、NKp46MFI水平在急乙肝恢复后有下降趋势,CD56dim NK、IFNAR2＋ NK和NKp46＋ NK细胞频数则呈上升趋势.在AHB组,HBV DNA与ALT呈正相关,而在急乙肝恢复前后：△HBV DNA和△ALT、△NK/LY（％）呈正相关;△ALT与△NKp46high NK频数、△NKp46MFI、△IFNAR2MFI呈正相关.结论 在慢性乙型肝炎免疫活动期,外周血NK细胞活性弱,而急性乙型肝炎中NK细胞在清除病毒,介导肝组织炎症损伤中发挥主导作用.

Objective To investigate the differences in frequency and function of natural killer cells （NK） between chronic hepatitis B （CHB） and acute hepatitis B （AHB）.Methods Patients with AHB and those with CHB in immune active （IA） phase were enrolled.The frequencies of NK,CD56dim NK,CD56bright NK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase,patients with AHB,and those recovered from AHB.At the same time,their correlations with ALT,HBV DNA and HBV markers were analyzed.Results Between IA and AHB,the frequencies of NK cells and NKp46dim NK cells in AHB cases were significantly lower than those in IA cases,but the frequency of NKp46high NK cells in AHB was higher than that in IA.For patients who recovered from AHB,the frequency of NK cells and NKp46dim NK cells increased;the varied ranges of frequencies of CD56dim NK,IFNAR2＋ NK and NKp46 ＋ NK cells were on the rise,while the frequency of NKp46high NK cells decreased after the recovery from AHB,and the varied ranges of CD56bright NK and IFNAR2MFI,NKp46MFI decreased.In AHB,HBVDNA loads were positively correlated with ALT levels.Before and after the recovery of AHB：△HBV DNA and △ALT,△ NK/LY （%） were positively correlated;△ALT and △NKp46high NK/NK（%）,△NKp46MFI,△IFNAR2MFI were positively correlated.Conclusions In CHB immune active phase,the activity of peripheral blood NK cells was too weak to remove the virus,but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.