Abstract
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.
Keywords: Autoimmune hepatitis; CD8+ T cell; COVID-19; Immunosuppression; Vaccination; Virus-specific T cell.
【저자키워드】 COVID-19, vaccination, Immunosuppression, CD8+ T cell, Autoimmune hepatitis, virus-specific T cell, 【초록키워드】 SARS-CoV-2, Inflammation, Immunity, antibody, T cells, SARS-COV-2 infection, severity, immunoglobulins, B cells, ELISA, immune, Peripheral blood, T cell, Laboratory results, COVID-19 vaccination, Hepatitis, pathophysiology, immune profiling, imaging, male, Patient, phenotype, Autoimmune, bimodal, distribution, liver, Plasma cell, BNT162b2 mRNA vaccination, SARS-CoV-2 vaccination, Immune-mediated, CD4 T cells, CD8 T cell, Liver disease, Cytometry, Flow, immune correlates, tissue, individual, CD8+, systemic steroids, myeloid cell, controls, feature, Cell, reactive, described, identify, was performed, activated, contribute, occur, unique, correlated, elicit, presenting, dissect, accumulate, CD8 T-cell, activated T cell, intrahepatic, 【제목키워드】 Hepatitis, SARS-CoV-2 vaccination, dominant, elicit, CD8 T-cell,