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 4

Phenotype of CD45+ immune subsets in the liver.

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Phenotype of CD45+ immune subsets in the liver. (A) Greater HLA DR and/o...
(A) Greater HLA DR and/or CD45RO expression by hepatic immune subsets from IA compared with IT subjects. Median percentages of cells expressing various phenotype markers within each immune subset are shown as a heatmap from IA (n = 28) and IT (n = 6) groups. Significant percentage differences between IA and IT subjects (with P values < 0.00625 by Mann-Whitney U test) are highlighted in bold font with thick borders. (B) Portal enrichment for immune subsets with activation phenotype. Heatmap represents percentages of lobular (L) and portal (P) immune subsets that express various phenotype markers from individual IA and IT subjects, with median percentages indicated for significant phenotype differences between lobular and portal immune subsets (P < 0.00625 by nonparametric signed-rank test). (C) Immune phenotype correlations with clinical and histological measures. Heatmaps show Spearman’s correlation coefficients (*rs) comparing serum ALT, HBV DNA, and age with percentages of cells expressing various markers in 6 CD45+ immune subsets. Correlations associated with significant P values below 0.0625 are indicated with thick/black borders. Positive and negative values of correlation coefficient corresponding to the red to blue colors are indicated for reference, with cutoff rs values (± 0.46) shown. P values associated with the correlation coefficients are provided in Supplemental Figure 4.