title: Mutation in the S gene of hepatitis B virus and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in patients with chronic hepatitis B virus infection.
abstract: The mechanism for the co-existence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in chronic HBV infected patients remains controversial. This study aimed to explore the role of HBV S gene mutation and anti-HBs subtype-nonspecificity in patients with simultaneous HBsAg/anti-HBs positivity. Chronic HBV infections with (n = 145, group I) and without (n = 141, group II) anti-HBs were included. The S gene was amplified and sequenced. The neutralization experiment was used in group I patients' sera to determine the specificity of anti-HBs. Additionally, the HBV vaccinated persons' sera were used to estimate the neutralize capacity of anti-HBs against HBsAg in group I patients. Results showed that 2.63% (145/5513) chronic HBV infected patients had positive results for anti-HBs. HBsAg amino acid (aa) substitution rate in 35 patients of group I was significantly higher than that in 58 patients of group II (1.89% vs 0.95%, P < 0.05), especially within "a" determinant (4.05% vs 1.22%, P < 0.05). In group I patients, anti-HBs in (74.29%, 26/35) patients was not directed to the subtypes of the co-existing HBsAg. Besides, some HBsAg variations in group I patients, sG145R mutation, inserted mutations, and continuous aa mutations within the major hydrophilic region (MHR), decreased the neutralized capacity of anti-HBs from HBV vaccinated persons. In conclusion, both of HBsAg mutation and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in chronic HBV infection. HBV vaccine recipients may still have a risk of HBV infection when exposure to patients with simultaneous HBsAg/anti-HBs positivity.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|First Clinical College, Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Jinpiao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|First Clinical College, Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xun
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|First Clinical College, Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Tianbin
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.|The Genetic Diagonstic Laboratory, The First Affiliated Hospital of Fujian Medical University, China.
authors.forename: Qishui
authors.identifier: 0000-0002-9923-3212
authors.initials: Q
authors.lastname: Ou
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000097:blood / Q000235:genetics; D009154:Mutation; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D050505:Mutant Proteins
keywords: antibodies to HBsAg; co-existence; hepatitis B surface antigen; mutation; serotype