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J Viral Hepat. 2016 Dec 23. doi: 10.1111/jvh.12667. [Epub ahead of print]
Antibody-dependent and -independent uptake of HBsAg across human leukocyte subsets is similar between individuals with chronic hepatitis B Virus infection and healthy donors.Tharinger H1, Rebbapragada I1, Samuel D2, Novikov N2, Nguyen M3, Jordan R4, Frey CR1, Pflanz S1.
Author information
- 1Department of Immunology, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
- 2Biology Core Support , Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
- 3Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Palo Alto, CA, 94304, USA.
- 4Discovery Virology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
AbstractMaintaining detectable levels of antibodies to hepatitis B surface antigen (HBsAg) in serum, i.e. HBsAg sero-conversion, is the key clinical endpoint indicative of recovery from infection with hepatitis B virus (HBV). HBV-infected hepatocytes secrete HBsAg sub-viral particles in vast excess over HBV virions. Therefore, detectable hepatitis B surface antibody (anti-HBs) titers imply complete elimination of HBV virions as well as HBsAg particles. Although intrahepatic phagocytes, e.g. Kupffer cells, are thought to mediate clearance of HBsAg via antibody (Ab)-dependent and -independent mechanisms, the relative contributions of circulating phagocytic cell types to HBsAg elimination are poorly characterized. Understanding the role of various immune cell subsets in the clearance of HBsAg is important because Ab-dependent or -independent phagocytic HBsAg uptake may modulate presentation of HBsAg-derived epitopes to antigen-specific T cells and hence plays a critical role in adaptive immunity against HBV. This study aims to characterize phagocytic leukocyte subsets capable of internalizing HBsAg immune complexes (HBsAg:IC) or un-complexed HBsAg particles in whole blood directly ex vivo. The data shows that uptake of HBsAg:IC occurs most prominently in monocytes, B cells, dendritic cells, and in neutrophils. In contrast, B cells, and to a lesser degree also monocytes, seem to be effective phagocytes for un-complexed HBsAg. Importantly, a similar pattern of phagocytic HBsAg uptake was observed in blood from chronic hepatitis B (CHB) patients compared to healthy controls, suggesting that phagocytosis-related cellular functions are not altered in the context of CHB. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS: CHB; HBV; Phagocytes; immune complexes
PMID:28012213DOI:10.1111/jvh.12667
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