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Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV.

Abstract：

BACKGROUND & AIMS:Little is known about the frequency, phenotype and function of HBV-specific B cells during chronic infection. Here we study HBcAg and HBsAg-specific B cells in different clinical phases of a chronic HBV infection. METHODS:We included 118 treatment naïve and 34 nucleos(t)ide analogue-treated patients with chronic HBV and 23 healthy HBsAg-vaccinated controls. Global and HBV-specific B lymphocytes were examined by FACS using fluorescently labeled HBsAg and HBcAg as baits. Functional HBV-specific B cell responses were quantified in B cell ELISPOT assays. Anti-HBs and anti-HBc antibodies were measured in serum and in ELISPOT supernatant by ELISA. RESULTS:Higher HBcAg-directed B cell responses were found in HBV clinical phases with elevated vs. low serum alanine aminotransferase (ALT) levels, irrespective of the HBeAg-status. In contrast, HBsAg-directed responses were lower and did not significantly fluctuate. In individual patients a mean 17.8-fold more circulating B cells target HBcAg than HBsAg baits. These HBcAg-specific B cells present a classical memory B cell profile and have slightly higher CD69 expression levels compared to global memory B cells. Viral suppression and ALT normalization upon treatment led to a numeric and functional reduction of HBcAg-specific B cell responses, accompanied by progressive decreases in serum anti-HBc antibodies. CONCLUSION:HBcAg-specific memory B cells present a classical memory B cell phenotype, vary in number and function throughout HBV's natural history and are significantly reduced during antiviral treatment. LAY SUMMARY:In recent years, studies examining the role of B cells during chronic hepatitis B virus infection have regained interest. We show that circulating B cells more often target the hepatitis B core antigen than the hepatitis surface antigen. Moreover, these hepatitis B core-specific B cells associate with the natural history of chronic HBV, and their responses decline during effective antiviral treatment.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Vanwolleghem T,Groothuismink ZMA,Kreefft K,Hung M,Novikov N,Boonstra A

doi

10.1016/j.jhep.2020.01.024

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

52-61

issue

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(20)30071-4

journal_volume

pub_type

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Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV.