Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection
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 patte...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1063616/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ying Yan |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-cfae219fa21440a894498de8b82ebae3 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T15:51:44Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-cfae219fa21440a894498de8b82ebae32022-12-22T04:15:17ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-11-011310.3389/fmicb.2022.10636161063616Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infectionYing Yan0Ying Yan1Huizhen Sun2Huizhen Sun3Huizhen Sun4Le Chang5Le Chang6Huimin Ji7Huimin Ji8Xinyi Jiang9Xinyi Jiang10Xinyi Jiang11Shi Song12Shi Song13Shi Song14Yingzi Xiao15Yingzi Xiao16Yingzi Xiao17Kaihao Feng18Kaihao Feng19Kaihao Feng20Abudulimutailipu Nuermaimaiti21Abudulimutailipu Nuermaimaiti22Abudulimutailipu Nuermaimaiti23Zhuoqun Lu24Zhuoqun Lu25Lunan Wang26Lunan Wang27Lunan Wang28National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaNational Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, ChinaBeijing Engineering Research Center of Laboratory Medicine, Beijing, ChinaGraduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaIntroductionOccult 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.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1063616/fulloccult HBV infectioncirculating immune complexesimmune escape mutationsLumipulse HBsAg-HQ assayHBeAg |
| spellingShingle | 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 Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection Frontiers in Microbiology occult HBV infection circulating immune complexes immune escape mutations Lumipulse HBsAg-HQ assay HBeAg |
| title | Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection |
| title_full | Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection |
| title_fullStr | Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection |
| title_full_unstemmed | Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection |
| title_short | Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection |
| title_sort | circulating immune complexes and mutations of hbsag are associated with the undetectable hbsag in anti hbs and hbeag positive occult hepatitis b virus infection |
| topic | occult HBV infection circulating immune complexes immune escape mutations Lumipulse HBsAg-HQ assay HBeAg |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1063616/full |
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