Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul Metropolitan Public Cord Blood Bank-ALLCORD, Seoul, Republic of Korea.
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Vaccine. 2014 Sep 29;32(43):5638-44. doi: 10.1016/j.vaccine.2014.08.007. Epub 2014 Aug 19.
Hepatitis B virus (HBV) vaccination is the most effective means of countering HBV-related morbidity and mortality, and individuals who do not respond to vaccination (non-responders) are problematic. The aim of the present study was to investigate associations between HLA and responsiveness to HBV vaccine in Korean infants. A total of 944 healthy Korean infants 9-12 months old were enrolled, and HLA distribution was compared among subgroups in accordance with the response to HBV vaccination. The HLA distribution of the subjects was similar to known Korean population data and did not deviate from the HWE proportions. The alleles that showed positive associations with non-responsiveness (<10mIU/mL) or low antibody titer (<100mIU/mL) were HLA-A33, B62, DRB104, and DRB107, while the alleles A02 and DRB108 showed negative associations. Among these alleles, B62, DRB107 and DRB108(-) showed significant associations with a poor or decreased response to vaccination even after correction (OR=1.83, 1.99, 5.63; pc<0.05) and also showed dose effects. After stratification by other associated alleles at different loci, B62 and DRB107 were independently associated with non-responsiveness, but A02(-) and DRB108(-) lost their individual associations. The combined association of A02(-)-DRB108(-) and B62-DRB108(-) was significant (OR=25.2 and 24.5; pc<0.05). Although the hierarchy is not clear, we can assume the following: (i) B62 and DRB107 have independent effects, (ii) DRB108(-) has a very strong and synergic effect, and (iii) there is probability of a third factor controlling A02(-) and DRB1*08(-) with an effect on non-responsiveness to HBV vaccination in Korean infants.
乙型肝炎病毒 (HBV) 疫苗接种是对抗 HBV 相关发病率和死亡率的最有效手段，而对疫苗无反应（无应答者）的个体则存在问题。本研究旨在探讨 HLA 与韩国婴儿对 HBV 疫苗反应之间的关系。共纳入 944 名 9-12 个月龄的健康韩国婴儿，并根据 HBV 疫苗接种反应对亚组进行比较，分析 HLA 分布。研究对象的 HLA 分布与已知的韩国人群数据相似，未偏离 HWE 比例。与无应答（<10mIU/mL）或低抗体滴度（<100mIU/mL）呈正相关的等位基因有 HLA-A33、B62、DRB104 和 DRB107，而 A02 和 DRB108 等位基因则呈负相关。在这些等位基因中，B62、DRB107 和 DRB108(-)即使在校正后，与疫苗接种反应不良或降低仍有显著相关性（OR=1.83、1.99、5.63；pc<0.05），且具有剂量效应。在按不同部位其他相关等位基因分层后，B62 和 DRB107 与无应答独立相关，但 A02(-)和 DRB108(-)失去了个体相关性。A02(-)-DRB108(-)和 B62-DRB108(-)联合相关性显著（OR=25.2 和 24.5；pc<0.05）。虽然层次结构尚不清楚，但我们可以假设：（i）B62 和 DRB107 具有独立作用；（ii）DRB108(-) 具有非常强的协同作用；（iii）存在第三种因素控制 A02(-) 和 DRB1*08(-)，对韩国婴儿对 HBV 疫苗的无反应性有影响。
