Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare and severe complication of SARS-CoV-2 infection that is characterized by multi-organ involvement and substantial inflammation. Direct testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Little is known about how antibody-mediated cellular responses in MIS-C compared to acute COVID-19 infection. Using high dimensional flow cytometry, we show that monocytes in MIS-C were hyperfunctional for antibody-dependent cellular phagocytosis and production of proinflammatory cytokines. In contrast, natural killer (NK) cells in MIS-C were hypofunctional for antibody-dependent cellular cytotoxicity and cytokine production. To provide some preliminary insight into mechanism, we show multiple ways leading to decreased cytotoxicity for NK cells, including phenotypic exhaustion of NK cells, variants in CD16 genetics that reduce Fc binding to IgG, and cytokine-induced associations. Using a novel anti-CD16 novel bispecific reagent that we developed, we could rescue the hypofunctional antibody-mediated NK cell function in MIS-C to the same levels as control. Together, our results reveal unique dysregulation in antibody-mediated responses in MIS-C that contribute to the immune pathology of this disease and may be amenable to immunomodulation.
Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C)
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Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1