不同乙型肝炎病毒感染者中人类白细胞抗原DR基因的表达水平

The characteristics of human leukocyte antigen-DR expression in patients with different outcomes of HBV infection

目的研究不同乙型肝炎病毒（hepatitis B virus，HBV）感染转归者外周血单个核细胞（peripheral blood mononuclear cells，PBMCs）中HLA-DR mRNA表达水平的差异。方法收集哈尔滨医科大学附属第二医院和哈尔滨市传染病院2012年5月至2015年11月感染科就诊的急性、慢性和隐性自限性HBV感染者101例和体检中心健康体检者（包括HBV疫苗免疫者和乙肝五项全阴者）53例；采用荧光定量PCR法检测了其外周血血浆中HBV-DNA含量和PBMCs中HLA-DR mRNA表达水平。结果在急性、慢性、隐性自限、疫苗免疫和五项全阴五组外周血PBMCs中HLA-DR mRNA的表达水平在隐性自限组最高，五项全阴组最低，总体比较差异显著（F＝3.901，P＝0.005）。其中，隐性自限组明显高于慢性组[（2.57±1.65）比（1.86±1.58），t＝2.016，P＝0.047]、疫苗免疫组[（2.57±1.65）比（1.69±1.35），t＝2.383，P＝0.020]和五项全阴组[（2.57±1.65）比（0.94±0.61），t＝4.881，P＝0.000]，而临界高于急性组[（2.57±1.65）比（1.39±1.23），t＝1.780，P＝0.084]；慢性组和疫苗免疫组也都有意义地高于五项全阴组[（1.86±1.58）比（0.94±0.61），t＝3.740，P＝0.000和（1.69±1.35）比（0.94±0.61），t＝2.215，P＝0.008]。在慢性HBV感染组，不同HBV-DNA水平组HLA-DR表达量整体无差异（F＝1.204，P＝0.319），但在（1.000-9.999）e＋005组HLA-DR表达量最高，临界意义地高于（5.000-9.999）e＋006组和≥ 1.000e＋007组[（1.000-9.999）e＋005比（5.000-9.999）e＋006，t＝1.769，P＝0.099；（5.000-9.999）e＋005比≥1.000e＋007，t＝2.114，P＝0.053]；在携带、轻度、中度和重度慢性HBV感染分组中，以及HBeAg^＋和HBeAg^－分组中HLA-DR表达量总体和两组间均无统计学差异。结论不同HBV感染和疫苗免疫均诱导了HLA-DR表达量增高，尤其在清除HBV感染状态下；在慢性HBV感染中HLA-DR表达可能与HBV-DNA水平相关。

Objective To investigate the expression of human leukocyte antigen-DR （HLA-DR） in peripheral blood mononuclear cells （PBMCs） of thepatients with different outcomes of hepatitis B virus （HBV infection.Methods 101 patients with different outcomes of HBV infection, including severe hepatitis B （SHB）, chronic hepatitis B （CHB）, and self-limited, were recruited from the Second Affiliated Hospital of Harbin Medical University and Harbin Infectious Disease Hospital.53 healthy individuals （with HBV vaccination and negative in all of the five-indexes for Hepatitis B detection） from healthexamination center wererecruitedas normal control from May 2012 to November 2015.The levelsof HBV-DNA in the plasma and HLA-DR in PBMCs were detected byreal-time quantitative PCR.Results Among the five groups （SHB, CHB, self-limited, hepatitis B vaccination, five-indexes of Hepatitis B negative）, the expression of HLA-DR was the highestin the self limited group, while it was the lowestin the five-indexes of Hepatitis B negative group（F=3.901, P=0.005）. More concretely, the expression of HLA-DR in self limited group was significantly higher than that in CHB group（2.57±1.65 vs 1.86±1.58, t=2.016, P=0.047）, hepatitis B vaccine group（2.57±1.65 vs 1.69±1.35, t=2.383, P=0.020）, five-indexes of Hepatitis B negative group （2.57±1.65 vs 0.94±0.61, t=4.881, P=0.000）, while expression of HLA-DRin SHB group （2.57±1.65 vs 1.39±1.23, t=1.780, P=0.084） was close tocritical value.The expression of HLA-DR in CHB group and hepatitis B vaccinationgroup was significantly higher than that of the five-indexes of Hepatitis B negative group （1.86±1.58 vs 0.94±0.61, t=3.740, P=0 and 1.69±1.35 vs 0.94±0.61, t=2.215, P=0.008）. There was no significant difference in the expression of HLA-DR between the groups with different HBV-DNA levels（F=1.204, P=0.319, but the expression of HLA-DR was the highest in（1.000-9.999）e＋ 005 group, and higher than（5.000-9.999）e＋ 006 and ≥ 1.000e＋ 007 group [（1.000-9.999） e＋ 005 vs （5.000-9.999） e＋ 006, t=1.769, P=0.099; （5.000-9.999）e＋ 005 vs ≥ 1.000e＋ 007, t=2.114, P=0.053] which nearly reached thecritical value.The expression of HLA-DR showed no significant difference between HBV carrier and patients with mild, moderate, and severe chronic HB.No significant differencewas observedfor the expression of HLA-DRbetween HBeAg^＋ and HBeAg^- patients.Conclusion HBV infection and vaccination induced increased expression of HLA-DR, especially in the clearance of HBV infection.In CHB, the expression of HLA-DR may be related to the level of HBV-DNA.