HLA-DRB1*09，11，12等位基因与乙肝疫苗免疫应答的相关性研究
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摘要
目的:探讨接种乙肝疫苗后机体免疫应答水平与HLA-DRB1等位基因HLA-DRB1*09,HLA-DRB1*11,HLA-DRB1*12的关系,为阐明乙肝疫苗免疫失败的免疫遗传学机理提供依据。
方法:选取入学时完成重组乙型肝炎疫苗标准全程接种(10μg/次,0、1、6月)的广西籍健康汉族大学生912名于半年内抽取外周血检测乙肝病毒血清学标志物(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc)及肝功能。对其中肝功能正常,其他病毒标志物阴性的无、弱应答(抗-HBs的S/N值<10)者另进行外周血HBV-DNA检测,阴性者再次接种重组乙型肝炎疫苗20μg,4周后检测HBV血清标志物,除抗-HBs外其它四项仍为阴性。根据抗-HBs滴度筛选出99名抗-HBs的S/N值<10的无、弱应答者,从中随机选取65人作为实验组;并从初次检测抗-HBs的S/N值≥10,肝功能正常及其它病毒标志物阴性的中、强应答者中随机选取96名作为对照组。以PCR-SSP法进行HLA-DRB1*09,HLA-DRB1*11,HLA-DRB1 *12等位基因的检测。
结果:无、弱应答组的HLA-DRB1*09基因的表达频率为21.54%,显著高于中、强应答组的9.38%(P=0.03);HLA-DRB1*11和HLA-DRB1*12基因在实验组和对照组中的表达频率分别是:16.92%和14.58%(P=0.688 )、15.38%和28.13%(P=0.059),两组比较接近显著性水平。
结论:1、HLA-DRB1*09基因与广西地区汉族人群乙肝疫苗无、弱应答相关;2、HLA-DRB1*11基因与广西地区汉族人群乙肝疫苗应答水平无明显相关性;3、HLA-DRB1*12基因可能与乙肝疫苗应答水平有一定的相关性。
Objective: To study the associations of HLA-DRB1 alleles HLA-DRB1*09, HLA-DRB1*11,HLA-DRB1*12 and the characteristic of immune response to hepatitis B vaccination, thus providing evidences to elucidate the immunogenetic mechanism of hepatitis B vaccination failure.
Methods: 912 healthy undergraduate students of Han nationality from Guangxi province, who had received a standard course of immunization with recombinant hepatitis B virus vaccine at month 0, 1 and 6 soon after the mission.After the whole course,they were tested HBV markers (HBsAg、anti-HBs、HBeAg、anti-HBe、anti-HBc) and liver function in a half-year. The non- or hypo-responders whose S/N of anti-HBs was less than 10 with normal liver function and with other HBV markers negative had been selected to receive another 20μg doses of recombinant HBsAg vaccination after tested the HBV-DNA in blood serum proved to be negative.Then they had a detection of serum HBV markers again four weeks later. The result showed that their HBV makers were still negative except anti-HBs. There were 99 persons whose S/N of anti-HBs still remained less than 10.In this crowd we chose 65 ones to be the non- or hypo-responders group randomly.For comparison,96 medium or hyper-responders(S/N of anti-HBs was greater than or equal to 10) with normal hepatic function and with other HBV markers negative at the primary test, were drawn randomly from the overage cohort as the controls.Detection of HLA-DRB1*09, HLA-DRB1*11 , HLA-DRB1*12 were performed by polymerase chain reaction using sequence specific primer (PCR-SSP).
Results: The allelic frequency of HLA-DRB1*09 in non- or hypo-responders group is significantly higher than that in medium or hyper-responders group(21.54 % vs 9.38 % ,P=0.03).While the allelic frequencies of HLA-DRB1*11 and HLA-DRB1*12 in the two groups are 16.92% vs 14.58% (P=0.688) and 15.38% vs 28.13%(P=0.059),close to the level of significance.
Conclusions: 1.HLA-DRB1*09 gene is related to Non- or hypo-response to HBV vaccine in population of Han nationality from Guangxi province. 2. No definite relationship has been found in HLA-DRB1*11 gene and the level of immune response to hepatitis B vaccine in population of Han nationality from Guangxi province. 3.HLA-DRB1*12 gene may has a certain correlation with immune response to hepatitis B vaccine.
方法:选取入学时完成重组乙型肝炎疫苗标准全程接种(10μg/次,0、1、6月)的广西籍健康汉族大学生912名于半年内抽取外周血检测乙肝病毒血清学标志物(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc)及肝功能。对其中肝功能正常,其他病毒标志物阴性的无、弱应答(抗-HBs的S/N值<10)者另进行外周血HBV-DNA检测,阴性者再次接种重组乙型肝炎疫苗20μg,4周后检测HBV血清标志物,除抗-HBs外其它四项仍为阴性。根据抗-HBs滴度筛选出99名抗-HBs的S/N值<10的无、弱应答者,从中随机选取65人作为实验组;并从初次检测抗-HBs的S/N值≥10,肝功能正常及其它病毒标志物阴性的中、强应答者中随机选取96名作为对照组。以PCR-SSP法进行HLA-DRB1*09,HLA-DRB1*11,HLA-DRB1 *12等位基因的检测。
结果:无、弱应答组的HLA-DRB1*09基因的表达频率为21.54%,显著高于中、强应答组的9.38%(P=0.03);HLA-DRB1*11和HLA-DRB1*12基因在实验组和对照组中的表达频率分别是:16.92%和14.58%(P=0.688 )、15.38%和28.13%(P=0.059),两组比较接近显著性水平。
结论:1、HLA-DRB1*09基因与广西地区汉族人群乙肝疫苗无、弱应答相关;2、HLA-DRB1*11基因与广西地区汉族人群乙肝疫苗应答水平无明显相关性;3、HLA-DRB1*12基因可能与乙肝疫苗应答水平有一定的相关性。
Objective: To study the associations of HLA-DRB1 alleles HLA-DRB1*09, HLA-DRB1*11,HLA-DRB1*12 and the characteristic of immune response to hepatitis B vaccination, thus providing evidences to elucidate the immunogenetic mechanism of hepatitis B vaccination failure.
Methods: 912 healthy undergraduate students of Han nationality from Guangxi province, who had received a standard course of immunization with recombinant hepatitis B virus vaccine at month 0, 1 and 6 soon after the mission.After the whole course,they were tested HBV markers (HBsAg、anti-HBs、HBeAg、anti-HBe、anti-HBc) and liver function in a half-year. The non- or hypo-responders whose S/N of anti-HBs was less than 10 with normal liver function and with other HBV markers negative had been selected to receive another 20μg doses of recombinant HBsAg vaccination after tested the HBV-DNA in blood serum proved to be negative.Then they had a detection of serum HBV markers again four weeks later. The result showed that their HBV makers were still negative except anti-HBs. There were 99 persons whose S/N of anti-HBs still remained less than 10.In this crowd we chose 65 ones to be the non- or hypo-responders group randomly.For comparison,96 medium or hyper-responders(S/N of anti-HBs was greater than or equal to 10) with normal hepatic function and with other HBV markers negative at the primary test, were drawn randomly from the overage cohort as the controls.Detection of HLA-DRB1*09, HLA-DRB1*11 , HLA-DRB1*12 were performed by polymerase chain reaction using sequence specific primer (PCR-SSP).
Results: The allelic frequency of HLA-DRB1*09 in non- or hypo-responders group is significantly higher than that in medium or hyper-responders group(21.54 % vs 9.38 % ,P=0.03).While the allelic frequencies of HLA-DRB1*11 and HLA-DRB1*12 in the two groups are 16.92% vs 14.58% (P=0.688) and 15.38% vs 28.13%(P=0.059),close to the level of significance.
Conclusions: 1.HLA-DRB1*09 gene is related to Non- or hypo-response to HBV vaccine in population of Han nationality from Guangxi province. 2. No definite relationship has been found in HLA-DRB1*11 gene and the level of immune response to hepatitis B vaccine in population of Han nationality from Guangxi province. 3.HLA-DRB1*12 gene may has a certain correlation with immune response to hepatitis B vaccine.
引文
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