T Cell Cross-reactivity in Autoimmune-like Hepatitis Triggered by COVID-19, 2023, Wang et al

T Cell Cross-reactivity in Autoimmune-like Hepatitis Triggered by COVID-19

Over 1,000 cases of pediatric hepatitis of unknown etiology have been reported worldwide since the first case was reported in the UK. To date, the etiology of pediatric hepatitis remains unknown and controversial. Adenovirus was first suspected to be the cause as it was present in the blood samples of the majority of cases. Partial cases have also been tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1].

However, it is still unclear how these viruses contribute to pediatric hepatitis. In the case of a pediatric patient with SARS-CoV-2 infection, the liver biopsy showed acute submassive hepatocyte necrosis, accompanied by a significant increase in T cell infiltration [2]. Furthermore, CD8 T-cell dominant hepatitis induced by coronavirus disease 2019 (COVID-19) vaccination has also been recently reported [3]. Although it is known that T cell receptors (TCRs) can discriminate between self- and non-self-antigens, it is now well-accepted that TCRs exhibit cross-reactivity toward similar and even distinct antigen peptides [4].

Thus, we hypothesized that following SARS-CoV-2 infection or vaccination, T cells carrying TCRs that recognize self-antigens undergo clonal expansion, which could eventually result in the onset of autoimmune-like hepatitis (Figure 1A).

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