HLA-DRB1＊15及相应位点下Th1／Th2细胞相关因子对乙肝疫苗免疫效果的影响

目的探讨广西人群HLA—DRB1＊15基因及相应位点下Th1／Th2细胞相关因子IFN-γIL-4对乙肝疫苗免疫应答水平的影响。方法选取完成重组乙型肝炎疫苗标准全程接种的广西籍汉族健康大学生中抗-HBsS／N值〈10mIU／ml的无、弱应答者80名（A组）作为研究对象，随机选取抗-HBsS／N值〉10mIU／ml的中、强应答者62名（B组）作为对照。应用PCR—SSP进行HLA-DRB1＊15等位基因的检测，采用酶联免疫吸附试验（ELISA）检测血清中Th1／Th2细胞相关因子干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）。结果①A组HLA—DRB1＊15基因表达频率为11．25％，显著低于B组的36．67％（P=0．001）；②A组中IFN-γ的平均表达水平为（6．28±6．84）pg／ml，显著低于B组（16．28±10．05）pg/ml（P=0．000）；③A组的IL-4平均表达水平为（2．36±1．91）pg／ml。显著低于B组（8．50±6．68）pg／ml（P=0．000）；④HLA—DRB1＊15阳性组IFN-γ平均表达水平为（13．82±9．89）pg／ml，显著高于HLA—DRB1＊15阴性组（9．76±9．54）pg／ml（P=0．029）；⑤HLA-DRB1＊15阳性组IL-4平均表达水平为（5．81±4．27）pg／ml，阴性组IL-4平均表达水平为（4．82±5．84）pg／ml，两组间差异无统计学意义（P=0．207）。结论①HLA—DRB1＊15基因可能是促进广西人群乙肝疫苗免疫应答的相关基因；②Th1／Th2细胞相关因子IFN-1、IL-4的表达水平可能影响机体乙肝疫苗的免疫效果；③HLA—DRBB1＊15基因可能是通过影响Th1细胞相关因子IFN-γ的表达水平，而不是通过影响Th2细胞相关因子IL-4的表达水平来影响乙肝疫苗的免疫应答。

Association of the immune response to hepatitis B vaccination with HLA-DRB1*15 allele as well as the expression of Th1/Th2 cytokines

Objective To elucidate the association of immune response to hepatitis B vaccination with HIA-DRB1 ＊ 15 allele as well as the levd of IFN-γ, IL-4 expressed by Th1/Th2 cells. Methods 80 vaecinees who had received standard courses of immunization with recombinant hepatitis B vaccination with non-or hypo-responders（ anti-HBs S/N 〈 10 mlU/ml） allocated to group A ,and 62 with medium or hyper-responders allocated to group B （anti-HBs S/N 〉 10mIU/ml） were drawn randomly from the subjects. HLA-DRB1 ＊ 15 was detected by PCR-SSP,and the level of IFN-γ IL-4 cytokines correlating to Th1/Th2 cells were examined by ELISA. Results （1）The allelic frequencies of HLA-DRB1 ＊ 15 was much lower in group A than group B （ 11.25 % vs 36.67 %, P = 0.001 ） ;（2）The expression level of IFN-γin group A （ 6.28 ±6.84 ） pg/ml was much less than lhat in group B （ 16.28 ±10.05 ） pg/ml （ P = 0. 000） ;（3）The expression level of IL-4 in group A （ 2.36 ±1.91 ） pg/ml was much less than that in group B （8.50 ±6.68）pg/ml（ P =0.000） ;（4） The expression level of IFN-γ in the HLA-DRB1＊15 negative group （9.76 ±9.54）pg/ml was less than that in the HLA-DRB1＊15 positive group （13.82 ± 9.89）pg/ml （P = 0. 029 ） ;（5） There was significant difference were seen betwecn the expression level of IL-.4 in the HLA-DRB1＊15 negative （4.82 ± 5.84 ） pg/ml and the positive （ 5.81 ± 4.27 ） pg/ml （ P = 0. 207 ）. Conclusions （1） HLA-DRB1＊15 might be the allele which enhanced immune response to hepatitis B vaccination in the population of Guangxi province;（2） The expression levels of IFN-γ and IL-4 correlating to Th1/Th2 cells might affect on the immune response to hepatitis B vaccination;（3） HLA-DRB1＊15 might play an important role in the response to hepatitis B vaccination by the expression of IFN-γ correlating to Th1 cells, while not by the expression of IL-4 correlating to Th2 cells.