肝炎肝硬化患者外周血自然杀伤细胞的变化与HLA-Cw基因型相关性研究

The relationship between the changes of peripheral blood natural killer cells and HLA-Cw alleles in liver cirrhotic patients with chronic HBV infection

目的研究乙型肝炎病毒（HBV）引起的肝炎肝硬化和急性乙型肝炎患者外周血自然杀伤细胞（NK）和活化NK细胞数量的变化及其与HLA-Cw基因型的关系。方法选择肝炎肝硬化和急性乙型肝炎发病期患者各30例及健康对照者41例，采用流式细胞仪检测外周血NK细胞和活化NK细胞的数量，并通过PCR-SSO（polymerase chain reaction-sequence specific oligonucleotide）的方法进行HLA-Cw的基因分型。结果肝炎肝硬化组NK细胞和活化NK细胞的数量分别是13．22％±4．6l％和45．68％±14．64％，均低于健康对照组（P〈0．05），急性乙型肝炎组NK细胞和活化NK细胞的数量分别是22．62％±3．70％和65．28％±14．45％，均较健康对照组增高（P〈0．05），且肝炎肝硬化组与急性乙型肝炎组比较差异有统计学意义（P〈0．01）；HLA-Cw＊15在肝炎肝硬化组中基因频率明显高于健康对照组（P〈0．05），且与活化NK细胞数量呈显著负相关（r=-0．862，P〈0．05），急性乙型肝炎组与健康对照组间HLA-Cw位点各等位基因的基因型差异无统计学意义（P〉0．05）。结论肝炎肝硬化患者NK细胞功能低下，HLA-Cw＊15基因型可能是通过影响NK细胞而导致HBV感染持续存在的原因之一。

Objective To investigate the relationship between the frequency of peripheral blood natural killer cells （NK） and HLA-Cw alleles in liver cirrhotic patients with chronic HBV infection and acute hepatitis B patients. Methods Thirty liver cirrhotic patients and 30 patients with acute hepatitis B were included in our study, and 41 healthy individuals were enrolled as controls. The numbers of circulating NK cells and activated NK cells were analyzed by flow cytometry. HLA-Cw genotyping was conducted with polymerase chain reaction-sequence specific oligonucleotide （PCR-SSO）. Results The numbers of circulating NK cells and activated NK cells in liver cirrhotic patients were 13.22%±4.61% and 45.68%±14.64%, which was lower than that in healthy subjects （P 〈 0.05）. The numbers of circulating NK cells and activated NK cells in acute hepatitis B patients were 22.62%±3.70% and 65.28% ±14.45% , which was higher than that in healthy subjects（P 〈 0.05）. There were statistically significant differences between the two groups（P 〈0.01 ）. The allele frequency of HLA-Cw＊15 in the patients with cirrhosis was significantly higher than that in the healthy（ P 〈 0.05 ）, and there was a significant negative correlation between the frequency of HLA-Cw＊15 and the numbers of activated NK cells in liver cirrhosis （r=-0.862, P〈0.05）. No statistically significance was found between the group of acute hepatitis B and healthy subjects about HLA-Cw（P〉0.05）. Conclusion The function of NK cells in liver cirrhotic patients is low,HLA-Cw＊15 gene may be one of the causes of effecting the antiviral function of NK cells to induce the persistence of hepatitis B virus（HBV） infection.