Abstract
Background
Hepatitis B surface antigen (HBsAg) is used as a clinical marker of hepatitis B virus (HBV) infection. However, conventional HBsAg assays have so far failed to accurately detect HBsAg in blood because of interference by patient-derived antibodies against HBsAg (HBsAb).
Methods
We developed a novel, fully automated assay system that can detect total HBsAg in blood, including antigens complexed with HBsAb. The immunoassay inactivates HBsAb via a simple pretreatment step to dissociate the HBsAg molecule from HBsAg–HBsAb complexes and thereby estimate total HBsAg. Accordingly, the test has been termed the “immunoassay for total antigen including complex via pretreatment (iTACT)-HBsAg.”
Results
The recovery rate of HBsAg in the presence of HBsAb was greater than 87 % at a cutoff value set at 5.0 mIU/mL on the basis of data from 545 healthy controls. Analyses using serial serum samples from 25 HBV carriers who became negative for HBsAg during follow-up showed that the iTACT-HBsAg could detect HBsAg over a period of years despite a loss in detection by conventional assays and was able to detect HBsAg in 39 (53 %) of 73 samples with HBsAb.
Conclusions
The new iTACT-HBsAg assay appears to detect total HBsAg with high sensitivity, even in the presence of HBsAb, and may useful in identifying subclinical or occult HBV carriers.
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Abbreviations
- ALP:
-
Alkaline phosphatase
- CLEIA:
-
Chemiluminescent enzyme immunoassay
- HBcAb:
-
Hepatitis B core antibody
- HBsAb:
-
Hepatitis B surface antibody
- HBsAg:
-
Hepatitis B surface antigen
- HBV:
-
Hepatitis B virus
- HCV:
-
Hepatitis C virus
- iTACT:
-
Immunoassay for total antigen including complex via pretreatment
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Acknowledgments
This research was supported in part by research grants (15fk0210035h0001 and 15fk0310012h0004) from the Japan Agency for Medical Research and Development. We thank Trevor Ralph for his English editorial assistance.
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Masayasu Imaizumi, Kazushige Moriyama, and Katsumi Aoyagi are employees of Fujirebio, Inc. Takehiko Ishida and Katsumi Aoyagi are employees of Advanced Life Science Institute, Inc. Yasuhito Tanaka received lecture fees from Fujirebio, Inc., Chugai Pharmaceutical Co. Ltd, Bristol-Myers K.K, and GlaxoSmithKline K.K. Yasuhito Tanaka received a research grant from Chugai Pharmaceutical Co. Ltd. Hiroshi Yastuhashi received commercial research funding from Chugai Pharmaceutical Co. Ltd.
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Matsumoto, A., Imaizumi, M., Tanaka, Y. et al. Novel and highly sensitive immunoassay for total hepatitis B surface antigen, including that complexed with hepatitis B surface antibody. J Gastroenterol 52, 376–384 (2017). https://doi.org/10.1007/s00535-016-1244-7
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DOI: https://doi.org/10.1007/s00535-016-1244-7