Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection

Ying Yan; Ying Yan; Huizhen Sun; Huizhen Sun; Huizhen Sun; Le Chang; Le Chang; Huimin Ji; Huimin Ji; Xinyi Jiang; Xinyi Jiang; Xinyi Jiang; Shi Song; Shi Song; Shi Song; Yingzi Xiao; Yingzi Xiao; Yingzi Xiao; Kaihao Feng; Kaihao Feng; Kaihao Feng; Abudulimutailipu Nuermaimaiti; Abudulimutailipu Nuermaimaiti; Abudulimutailipu Nuermaimaiti; Zhuoqun Lu; Zhuoqun Lu; Lunan Wang; Lunan Wang; Lunan Wang

doi:10.3389/fmicb.2022.1063616

Frontiers in Microbiology (Nov 2022)

Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection

Ying Yan,
Ying Yan,
Huizhen Sun,
Huizhen Sun,
Huizhen Sun,
Le Chang,
Le Chang,
Huimin Ji,
Huimin Ji,
Xinyi Jiang,
Xinyi Jiang,
Xinyi Jiang,
Shi Song,
Shi Song,
Shi Song,
Yingzi Xiao,
Yingzi Xiao,
Yingzi Xiao,
Kaihao Feng,
Kaihao Feng,
Kaihao Feng,
Abudulimutailipu Nuermaimaiti,
Abudulimutailipu Nuermaimaiti,
Abudulimutailipu Nuermaimaiti,
Zhuoqun Lu,
Zhuoqun Lu,
Lunan Wang,
Lunan Wang,
Lunan Wang

Affiliations

Ying Yan: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Ying Yan: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Huizhen Sun: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Huizhen Sun: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Huizhen Sun: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Le Chang: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Le Chang: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Huimin Ji: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Huimin Ji: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Xinyi Jiang: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Xinyi Jiang: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Xinyi Jiang: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Shi Song: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Shi Song: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Shi Song: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Yingzi Xiao: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Yingzi Xiao: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Yingzi Xiao: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Kaihao Feng: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Kaihao Feng: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Kaihao Feng: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Abudulimutailipu Nuermaimaiti: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Abudulimutailipu Nuermaimaiti: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Abudulimutailipu Nuermaimaiti: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
Zhuoqun Lu: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Zhuoqun Lu: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Lunan Wang: National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
Lunan Wang: Beijing Engineering Research Center of Laboratory Medicine, Beijing, China
Lunan Wang: Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

DOI: https://doi.org/10.3389/fmicb.2022.1063616
Journal volume & issue: Vol. 13

Abstract

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IntroductionOccult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern.Methods2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs).Results1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found.DiscussionIn conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host’s selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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