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JCI Insight. 2021 Apr 08;6(7). doi: 10.1172/jci.insight.146883.

Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver.

JCI insight

Daniel Traum, Yue J Wang, Kathleen B Schwarz, Jonathan Schug, David Kh Wong, Harry LA Janssen, Norah A Terrault, Mandana Khalili, Abdus S Wahed, Karen F Murray, Phillip Rosenthal, Simon C Ling, Norberto Rodriguez-Baez, Richard K Sterling, Daryl Ty Lau, Timothy M Block, Michael D Feldman, Elizabeth E Furth, William M Lee, David E Kleiner, Anna S Lok, Klaus H Kaestner, Kyong-Mi Chang

Affiliations

  1. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  2. Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
  3. Biomedical Sciences, College of Medicine, Florida State University, Tallahasee, Florida, USA.
  4. Department of Pediatrics, UCSD, San Diego, California, USA.
  5. Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  6. Toronto Centre for Liver Disease, University of Toronto, Toronto, Ontario, Canada.
  7. Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
  8. Department of Medicine, UCSF, San Francisco, California, USA.
  9. University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
  10. Cleveland Clinic Pediatric Institute, Cleveland, Ohio, USA.
  11. Department of Pediatrics, UCSF, San Francisco, California, USA.
  12. The Hospital for Sick Children and Department of Paediatrics and University of Toronto, Toronto, Canada.
  13. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  14. Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
  15. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
  16. Baruch S. Blumberg Institute, Doylestown, Pennsylvania, USA.
  17. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  18. Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  19. Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
  20. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 33621209 PMCID: PMC8119221 DOI: 10.1172/jci.insight.146883

Abstract

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

Keywords: Adaptive immunity; Fibrosis; Hepatology; Infectious disease; Innate immunity

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