Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver
Daniel Traum, … , Klaus H. Kaestner, Kyong-Mi Chang
Daniel Traum, … , Klaus H. Kaestner, Kyong-Mi Chang
Published February 23, 2021
Citation Information: JCI Insight. 2021;6(7):e146883. https://doi.org/10.1172/jci.insight.146883.
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Research Article Hepatology Infectious disease

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

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.

Authors

Daniel Traum, Yue J. Wang, Kathleen B. Schwarz, Jonathan Schug, David K.H. Wong, Harry L.A. Janssen, Norah A. Terrault, Mandana Khalili, Abdus S. Wahed, Karen F. Murray, Phillip Rosenthal, Simon C. Ling, Norberto Rodriguez-Baez, Richard K. Sterling, Daryl T.Y. 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

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Figure 3

CD45+ adaptive and innate immune cells in the liver in HBV-infected and uninfected subjects.

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CD45+ adaptive and innate immune cells in the liver in HBV-infected and ...
(A) Stacked bar graphs show relative proportions of adaptive and innate immune subsets within total, lobular, and portal regions. (B) Hepatic concentrations of adaptive and innate immune subset per mm2 ROI are compared with each other, with Spearman’s correlation coefficients and P values shown in right upper part of each scatterplots. P < 0.0033 were considered significant and highlighted in red font. (C and D) Heatmaps showing Spearman’s correlation coefficients (rs) comparing total, lobular, and portal hepatic immune cell concentrations (in number of cells/mm2) to serum ALT (U/L), HBV DNA (log HBV DNA IU/mL), and histological Ishak scores among 28 IA and 6 IT subjects, and with %portal/total ROI as a measure of portal expansion. Correlations associated with P < 0.0083 are highlighted by bold font and black border. (E) Dot plots comparing 14 pediatric IA, 14 adult IA, 4 pediatric IT, and 2 adult IT subjects with chronic hepatitis B for median hepatic CD45+ immune cell density/mm2 in total, lobular, and portal region, with error bars indicating 25% and 75% IQRs. P values were calculated by Mann-Whitney U test. P < 0.00625 were considered significant and highlighted in red font. (F) Comparisons between age and total, lobular, and portal hepatic immune densities in 28 IA subjects, with Spearman’s correlation (rs) and P values shown in red font for P < 0.00625.