Shared TCR Vβ21.3+ T cell immunological signature between MIS-A and MIS-C

Multisystem inflammatory syndrome (MIS) is a severe and potentially life-threatening complication of SARS-CoV-2 infection that affects both children (MIS-C) and adults (MIS-A). While the inflammatory response in MIS-C has been studied in detail, the immune dysregulation underlying MIS-A remains poorly understood, mainly due to the rarity of its condition. Using flow cytometry, we analyzed the T cell response in two, Danish and French, MIS-A cohorts, encompassing a total of 16 cases. We observed an expansion of Vβ21.3+ T cells in at least one of the major T cell subsets (CD3+, CD4+, or CD8+) in 9 out of 16 MIS-A patients. Vβ21.3+ T cells showed increased expression of activation and exhaustion markers along with a higher abundance of effector memory T cells compared to their Vβ21.3-negative counterparts in patients with or without Vβ21.3 expansion. These findings demonstrate that MIS-A shares the same Vβ21.3+ T cell signature previously reported in MIS-C, suggesting a shared pathological immune-related mechanism between the two conditions.