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However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels &lt;500 (HBs<jats:sup>lo<\/jats:sup>) or &gt;50,000\u2009IU\/ml (HBs<jats:sup>hi<\/jats:sup>) using immunological assays (flow cytometry, ICS, ELISPOT). HBs<jats:sup>hi<\/jats:sup> patients had significantly higher expression of inhibitory PD-1 on CD4<jats:sup>+<\/jats:sup> T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBs<jats:sup>lo<\/jats:sup> patients had IFN\u03b3<jats:sup>+<\/jats:sup>TNF\u03b1<jats:sup>+<\/jats:sup> and IFN\u03b3<jats:sup>+<\/jats:sup> IL2<jats:sup>+<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cell responses respectively, in comparison to 33% and 13% of HBs<jats:sup>hi<\/jats:sup> patients. Checkpoint blockade with \u03b1PD-1 improved HBV-specific CD4<jats:sup>+<\/jats:sup> T cell function only in HBs<jats:sup>lo<\/jats:sup> patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet \u03b1PD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg &lt;100\u2009IU\/ml compared to patients with HBsAg &gt;5,000\u2009IU\/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4<jats:sup>+<\/jats:sup> T cell responses, and augmentation by checkpoint blockade.<\/jats:p>","DOI":"10.1038\/s41598-020-58870-2","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T11:02:47Z","timestamp":1580814167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients"],"prefix":"10.1038","volume":"10","author":[{"given":"Jin Hyang","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alip","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Ayithan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Romani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshi","family":"Khanam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang-June","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Rijnbrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Sofia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Kottilil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris B.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawna","family":"Poonia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,4]]},"reference":[{"key":"58870_CR1","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","volume":"67","author":"NA Terrault","year":"2018","unstructured":"Terrault, N. A. et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67, 1560\u20131599 (2018).","journal-title":"Hepatology"},{"key":"58870_CR2","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","volume":"67","author":"EASL 2017","year":"2017","unstructured":"EASL 2017. Clinical Practice Guidelines on the management of HBV infection_2017. Journal of Hepatology 67, 370\u2013398 (2017).","journal-title":"Journal of Hepatology"},{"key":"58870_CR3","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1002\/hep.1840130403","volume":"13","author":"Y-F Liaw","year":"1991","unstructured":"Liaw, Y.-F., Sheen, I.-S., Chen, T.-J., Chu, C.-M. & Pao, C.-C. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: A prospective study. 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All other authors declare there is no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1835"}}