Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.
Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.
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DOI：
10.1002/hep.29876
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Mizokami M
中科院分区：
文献类型：
--
作者：
Nishida N;Sugiyama M;Sawai H;Nishina S;Sakai A;Ohashi J;Khor SS;Kakisaka K;Tsuchiura T;Hino K;Sumazaki R;Takikawa Y;Murata K;Kanda T;Yokosuka O;Tokunaga K;Mizokami M
在接种基于乙型肝炎病毒（HBV）基因型C设计的乙型肝炎（HB）疫苗的个体中，约有5 - 10%未能获得保护水平的抗体。本研究通过全基因组关联研究（GWAS）和人类白细胞抗原（HLA）关联试验研究了乙肝疫苗低免疫应答背后的宿主遗传因素。GWAS和HLA相关性试验共对1193名日本人进行，包括107名低应答者，351名中级应答者和735名高应答者。经典HLA II类等位基因使用全基因组SNP分型数据进行统计推算。GWAS鉴定出HLA‐DRB1‐DQB1、HLA‐DPB1和BTNL2基因与基于HBV基因型c设计的HB疫苗的免疫应答之间的独立关联。在三组1,193例HB疫苗接种个体的比较中，5个HLA‐DRB1‐DQB1单倍型和2个DPB1等位基因与HB疫苗应答显著相关。当比较低免疫应答者和HBV患者之间DRB1 - DQB1单倍型和DPB1等位基因的频率时，发现了三个DRB1 - DQB1单倍型的显著相关性，而没有发现任何DPB1等位基因的相关性。相比之下，在高免疫应答者和健康个体之间的比较中，没有发现DRB1 - DQB1单倍型和DPB1等位基因的关联。结论：本研究的结果清楚地表明HLA‐DR‐DQ（即特异性DR‐DQ单倍型对疫苗相关的HB表面抗原（HBsAg）的识别）和BTNL2分子（即对HB疫苗的高免疫应答）对于基于HBV基因型c设计的HB疫苗的应答的重要性（Hepatology 2018）。
Approximately 5‐10% of individuals who are vaccinated with a hepatitis B (HB) vaccine designed based on the hepatitis B virus (HBV) genotype C fail to acquire protective levels of antibodies. Here, host genetic factors behind low immune response to this HB vaccine were investigated by a genome‐wide association study (GWAS) and Human Leukocyte Antigen (HLA) association tests. The GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders, 351 intermediate responders, and 735 high responders. Classical HLA class II alleles were statistically imputed using the genome‐wide SNP typing data. The GWAS identified independent associations of HLA‐DRB1‐DQB1, HLA‐DPB1 and BTNL2 genes with immune response to a HB vaccine designed based on the HBV genotype C. Five HLA‐DRB1‐DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1‐DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1‐DQB1 haplotypes, and no association was identified for any of the DPB1 alleles. In contrast, no association was identified for DRB1‐DQB1 haplotypes and DPB1 alleles in a comparison between high immune responders and healthy individuals. Conclusion: The findings in this study clearly show the importance of HLA‐DR‐DQ (i.e., recognition of a vaccine related HB surface antigen (HBsAg) by specific DR‐DQ haplotypes) and BTNL2 molecules (i.e., high immune response to HB vaccine) for response to a HB vaccine designed based on the HBV genotype C. (Hepatology 2018).
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影响因子：
3.7
作者：
Nishida N;Sawai H;Matsuura K;Sugiyama M;Ahn SH;Park JY;Hige S;Kang JH;Suzuki K;Kurosaki M;Asahina Y;Mochida S;Watanabe M;Tanaka E;Honda M;Kaneko S;Orito E;Itoh Y;Mita E;Tamori A;Murawaki Y;Hiasa Y;Sakaida I;Korenaga M;Hino K;Ide T;Kawashima M;Mawatari Y;Sageshima M;Ogasawara Y;Koike A;Izumi N;Han KH;Tanaka Y;Tokunaga K;Mizokami M
通讯作者：
Mizokami M
影响因子：
5.4
作者：
Thomas, Rasmi;Thio, Chloe L.;Carrington, Mary
通讯作者：
Carrington, Mary
影响因子：
4.5
作者：
Prescott NJ;Lehne B;Stone K;Lee JC;Taylor K;Knight J;Papouli E;Mirza MM;Simpson MA;Spain SL;Lu G;Fraternali F;Bumpstead SJ;Gray E;Amar A;Bye H;Green P;Chung-Faye G;Hayee B;Pollok R;Satsangi J;Parkes M;Barrett JC;Mansfield JC;Sanderson J;Lewis CM;Weale ME;Schlitt T;Mathew CG;UK IBD Genetics Consortium
通讯作者：
UK IBD Genetics Consortium
影响因子：
30.8
作者：
Hu, Zhibin;Liu, Yao;Shen, Hongbing
通讯作者：
Shen, Hongbing
影响因子：
6.7
作者：
Cheong, Hyun Sub;Lee, Jeong-Hoon;Kim, Yoon-Jun
通讯作者：
Kim, Yoon-Jun