title: Genetic polymorphisms of CXCR5 and CXCL13 are associated with non-responsiveness to the hepatitis B vaccine.
abstract: A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes (CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925) in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922, rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 "GG" genotype was associated with higher levels of CXCR5 than the "AG" and "AA" genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the "G" allele in rs3922 may lead to higher gene expression than the "A" allele, implicating that rs3922 might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism associated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination.
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
authors: Zhaojun
authors: Z
authors: Duan
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
authors: Xiangmei
authors: X
authors: Chen
authors: Department of Hepatitis Vaccine, National Institutes for Food and Drug Control, Beijing 100050, China.
authors: Zhenglun
authors: Z
authors: Liang
authors: Department of R&D, Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen 518057, Guangdong, PR China.
authors: Ying
authors: Y
authors: Zeng
authors: Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China.
authors: Fengcai
authors: F
authors: Zhu
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
authors: Lu
authors: L
authors: Long
authors: The Pirbright Institute, Pirbright, UK.
authors: Malcolm A
authors: MA
authors: McCrae
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
authors: Hui
authors: H
authors: Zhuang
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China. Electronic address: taoshen@bjmu.edu.cn.
authors: Tao
authors: T
authors: Shen
authors: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China. Electronic address: lu.fengmin@hsc.pku.edu.cn.
authors: Fengmin
authors: F
authors: Lu
mesh_terms: D000328:Adult; D054382:Chemokine CXCL13 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D017325:Hepatitis B Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054380:Receptors, CXCR5 / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D017211:Treatment Failure
chemical_list: C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D017325:Hepatitis B Vaccines; D054380:Receptors, CXCR5
keywords: CXCL13; CXCR5; Follicular T helper cell; Hepatitis B vaccine; Non-response; Polymorphism