@article{Butters2024,
abstract = {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.},
author = {Butters, Claire and Benede, Ntombi and Moyo-Gwete, Thandeka and Richardson, Simone I and Rohlwink, Ursula and Shey, Muki and Ayres, Frances and Manamela, Nelia P and Makhado, Zanele and Balla, Sashkia R and Madzivhandila, Mashudu and Ngomti, Amkele and Baguma, Richard and Facey-Thomas, Heidi and Spracklen, Timothy F and Day, Jonathan and {van der Ross Debbie}, Hamza and Riou, Catherine and Burgers, Wendy A and Scott, Christiaan and Zuhlke, Liesl and Moore, Penny L and Keeton, Roanne S and Webb, Kate},
doi = {10.1016/J.CLIM.2023.109877},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Butters et al. - 2024 - Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals dist.pdf:pdf},
issn = {1521-6616},
journal = {Clinical Immunology},
keywords = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {feb},
pages = {109877},
pmid = {38141746},
publisher = {Academic Press},
title = {{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}},
volume = {259},
year = {2024}
}

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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. 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