1-s2.0-S1521661623006411-main (1).pdf (2 MB)
Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals distinct inflammatory cytokine production and a monofunctional T cell response.
journal contributionposted on 2024-01-10, 12:54 authored by Claire Butters, Ntombi Benede, Thandeka Moyo-Gwete, Simone I Richardson, Ursula Rohlwink, Muki Shey, Frances Ayres, Nelia P Manamela, Zanele Makhado, Sashkia R Balla, Mashudu Madzivhandila, Amkele Ngomti, Richard Baguma, Heidi Facey-Thomas, Timothy F Spracklen, Jonathan Day, Hamza van der Ross, Catherine Riou, Wendy A Burgers, Christiaan Scott, Liesl Zühlke, Penny L Moore, Roanne S Keeton, Kate Webb
Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C is incompletely understood, with limited data comparing MIS-C to clinically similar paediatric febrile diseases at presentation. SARS-CoV-2-specific T cell responses have not been compared in these groups to assess whether there is a T cell profile unique to MIS-C. In this study, we measured inflammatory cytokine concentration and SARS-CoV-2-specific humoral immunity and T cell responses in children with fever and suspected MIS-C at presentation (n = 83) where MIS-C was ultimately confirmed (n = 58) or another diagnosis was made (n = 25) and healthy children (n = 91). Children with confirmed MIS-C exhibited distinctly elevated serum IL-10, IL-6, and CRP at presentation. No differences were detected in SARS-CoV-2 spike IgG serum concentration, neutralisation capacity, antibody dependant cellular phagocytosis, antibody dependant cellular cytotoxicity or SARS-CoV-2-specific T cell frequency between the groups. Healthy SARS-CoV-2 seropositive children had a higher proportion of polyfunctional SARS-CoV-2-specific CD4+ T cells compared to children with MIS-C and those with other inflammatory or infectious diagnoses, who both presented a largely monofunctional SARS-CoV-2-specific CD4+ T cell profile. Treatment with steroids and/or intravenous immunoglobulins resulted in rapid reduction of inflammatory cytokines but did not affect the SARS-CoV-2-specific IgG or CD4+ T cell responses in MIS-C. In these data, MIS-C had a unique cytokine profile but not a unique SARS-CoV-2 specific humoral or T cell cytokine response.