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SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis
BACKGROUND & AIMS: Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Herein, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Association for the Study of the Liver. Published by Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021033/ https://www.ncbi.nlm.nih.gov/pubmed/35461912 http://dx.doi.org/10.1016/j.jhep.2022.03.040 |
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author | Boettler, Tobias Csernalabics, Benedikt Salié, Henrike Luxenburger, Hendrik Wischer, Lara Salimi Alizei, Elahe Zoldan, Katharina Krimmel, Laurenz Bronsert, Peter Schwabenland, Marius Prinz, Marco Mogler, Carolin Neumann-Haefelin, Christoph Thimme, Robert Hofmann, Maike Bengsch, Bertram |
author_facet | Boettler, Tobias Csernalabics, Benedikt Salié, Henrike Luxenburger, Hendrik Wischer, Lara Salimi Alizei, Elahe Zoldan, Katharina Krimmel, Laurenz Bronsert, Peter Schwabenland, Marius Prinz, Marco Mogler, Carolin Neumann-Haefelin, Christoph Thimme, Robert Hofmann, Maike Bengsch, Bertram |
author_sort | Boettler, Tobias |
collection | PubMed |
description | BACKGROUND & AIMS: Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Herein, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT162b2 mRNA vaccination. We sought to identify the underlying immune correlates. The patient received oral budesonide, relapsed, but achieved remission under systemic steroids. METHODS: Imaging mass cytometry for spatial immune profiling was performed on liver biopsy tissue. Flow cytometry was performed to dissect CD8 T-cell phenotypes and identify SARS-CoV-2-specific and EBV-specific T cells longitudinally. Vaccine-induced antibodies were determined by ELISA. Data were correlated with clinical laboratory results. RESULTS: Analysis of the hepatic tissue revealed an immune infiltrate quantitatively dominated by activated cytotoxic CD8 T cells with panlobular distribution. An enrichment of CD4 T cells, B cells, plasma cells and myeloid cells was also observed compared to controls. The intrahepatic infiltrate showed enrichment for CD8 T cells with SARS-CoV-2-specificity compared to the peripheral blood. Notably, hepatitis severity correlated longitudinally with an activated cytotoxic phenotype of peripheral SARS-CoV-2-specific, but not EBV-specific, CD8+ T cells or vaccine-induced immunoglobulins. CONCLUSIONS: COVID-19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination-induced antigen-specific tissue-resident immunity requiring systemic immunosuppression. LAY SUMMARY: Liver inflammation is observed during SARS-CoV-2 infection but can also occur in some individuals after vaccination and shares some typical features with autoimmune liver disease. In this report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within the population of these liver-infiltrating T cells, we observed an enrichment of T cells that are reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to liver inflammation in this context. |
format | Online Article Text |
id | pubmed-9021033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | European Association for the Study of the Liver. Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90210332022-04-21 SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis Boettler, Tobias Csernalabics, Benedikt Salié, Henrike Luxenburger, Hendrik Wischer, Lara Salimi Alizei, Elahe Zoldan, Katharina Krimmel, Laurenz Bronsert, Peter Schwabenland, Marius Prinz, Marco Mogler, Carolin Neumann-Haefelin, Christoph Thimme, Robert Hofmann, Maike Bengsch, Bertram J Hepatol Research Article BACKGROUND & AIMS: Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Herein, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT162b2 mRNA vaccination. We sought to identify the underlying immune correlates. The patient received oral budesonide, relapsed, but achieved remission under systemic steroids. METHODS: Imaging mass cytometry for spatial immune profiling was performed on liver biopsy tissue. Flow cytometry was performed to dissect CD8 T-cell phenotypes and identify SARS-CoV-2-specific and EBV-specific T cells longitudinally. Vaccine-induced antibodies were determined by ELISA. Data were correlated with clinical laboratory results. RESULTS: Analysis of the hepatic tissue revealed an immune infiltrate quantitatively dominated by activated cytotoxic CD8 T cells with panlobular distribution. An enrichment of CD4 T cells, B cells, plasma cells and myeloid cells was also observed compared to controls. The intrahepatic infiltrate showed enrichment for CD8 T cells with SARS-CoV-2-specificity compared to the peripheral blood. Notably, hepatitis severity correlated longitudinally with an activated cytotoxic phenotype of peripheral SARS-CoV-2-specific, but not EBV-specific, CD8+ T cells or vaccine-induced immunoglobulins. CONCLUSIONS: COVID-19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination-induced antigen-specific tissue-resident immunity requiring systemic immunosuppression. LAY SUMMARY: Liver inflammation is observed during SARS-CoV-2 infection but can also occur in some individuals after vaccination and shares some typical features with autoimmune liver disease. In this report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within the population of these liver-infiltrating T cells, we observed an enrichment of T cells that are reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to liver inflammation in this context. European Association for the Study of the Liver. Published by Elsevier B.V. 2022-09 2022-04-21 /pmc/articles/PMC9021033/ /pubmed/35461912 http://dx.doi.org/10.1016/j.jhep.2022.03.040 Text en © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Research Article Boettler, Tobias Csernalabics, Benedikt Salié, Henrike Luxenburger, Hendrik Wischer, Lara Salimi Alizei, Elahe Zoldan, Katharina Krimmel, Laurenz Bronsert, Peter Schwabenland, Marius Prinz, Marco Mogler, Carolin Neumann-Haefelin, Christoph Thimme, Robert Hofmann, Maike Bengsch, Bertram SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title_full | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title_fullStr | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title_full_unstemmed | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title_short | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis |
title_sort | sars-cov-2 vaccination can elicit a cd8 t-cell dominant hepatitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021033/ https://www.ncbi.nlm.nih.gov/pubmed/35461912 http://dx.doi.org/10.1016/j.jhep.2022.03.040 |
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