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ResearchIn-Press PreviewHepatologyInfectious disease Open Access | 10.1172/jci.insight.146883

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

Daniel Traum,1 Yue J. Wang,2 Kathleen B. Schwarz,3 Jonathan Schug,1 David K.H. Wong,4 Harry L.A. Janssen,4 Norah A. Terrault,5 Mandana Khalili,6 Abdus S. Wahed,7 Karen F. Murray,8 Philip Rosenthal,9 Simon C. Ling,10 Norberto Rodriguez-Baez,11 Richard K. Sterling,12 Daryl T.Y. Lau,13 Timothy M. Block,14 Michael D. Feldman,15 Emma E. Furth,15 William M. Lee,16 David E. Kleiner,17 Anna S. Lok,18 Klaus H. Kaestner,19 and Kyong-Mi Chang20

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Traum, D. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Wang, Y. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Schwarz, K. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Schug, J. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Wong, D. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Janssen, H. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Terrault, N. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Khalili, M. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Wahed, A. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Rodriguez-Baez, N. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

Find articles by Sterling, R. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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1Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

2College of Medicine, Florida State University, Tallahassee, United States of America

3Department of Pediatrics, University of California, San Diego, San Diego, United States of America

4Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada

5Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, United States of America

6Department of Medicine, University of California, San Francisco, San Francisco, United States of America

7Department of Public Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, United States of America

8Pediatrics Institute, Cleveland Clinic, Cleveland, United States Minor Outlying Islands

9Department of Pediatrics, University of California, San Francisco, San Francisco, United States of America

10Department of Pediatrics, University of Toronto, Toronto, Canada

11Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, United States of America

12Department of Internal Medicine, Virginia Commonwealth University, Richmond, United States of America

13Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America

14Baruch S. Blumberg Institute, Doylestown, United States of America

15Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

16Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, United States of America

17Laboratory of Pathology, National Cancer Institute, Bethesda, United States of America

18Department of Internal Medicine, Univerisity of Michigan, Ann Arbor, United States of America

19Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadeplhia, United States of America

20Department of Medical Research, The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States of America

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Published February 23, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.146883.
Copyright © 2021, Traum et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 23, 2021 - Version history
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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 HBeAg+ chronic hepatitis B, we provide 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.

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