https://www.sciencedirect.com/science/article/pii/S0168827822002343
SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis
Highlights
-Identification of immune correlates in a case of mRNA vaccine-associated autoimmune hepatitis
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Imaging mass cytometry identifies intrahepatic panlobular enrichment of activated cytotoxic CD8 T cells
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Flow cytometry identifies intrahepatic enrichment of activated CD8 T cells with SARS-CoV-2-specificity
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Peripheral SARS-CoV-2-specific CD8 T cell activation correlates with ALT levels
Abstract
Background & Aims
Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Here, 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 and sought to identify the underlying immune correlates. The patient received first 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 was correlated with clinical labs.
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
COVID19 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.