Thomas Vanwolleghem1, Zwier M A Groothuismink2, Kim Kreefft2, Magdeleine Hung3, Nikolai Novikov3, Andre Boonstra2. 1. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium. Electronic address: thomas.vanwolleghem@uza.be. 2. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Department of Biology, Gilead Sciences, Foster City, United States of America.
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.
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 virusinfection 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.
Authors: Arzoo M Patel; Yuxin S Liu; Scott P Davies; Rachel M Brown; Deirdre A Kelly; Dagmar Scheel-Toellner; Gary M Reynolds; Zania Stamataki Journal: Front Immunol Date: 2021-09-23 Impact factor: 8.786
Authors: Arno Furquim d'Almeida; Erwin Ho; Stijn Van Hees; Thomas Vanwolleghem Journal: United European Gastroenterol J Date: 2021-11-30 Impact factor: 4.623