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
Year: 2023
Type: article
Study design: Observational Study
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.
Source: Clinical Immunology
Authors: 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
Institutions: University of Cape Town, Groote Schuur Hospital, Red Cross War Memorial Children's Hospital, Institute of Infectious Disease and Molecular Medicine, National Health Laboratory Service, University of the Witwatersrand, National Institute for Communicable Diseases, The Francis Crick Institute, Wellcome Centre for Infectious Diseases Research in Africa, South African Medical Research Council, Centre for the AIDS Programme of Research in South Africa
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,090
Funders: Wellcome Trust, Francis Crick Institute, Department of Science and Innovation, South Africa, Cancer Research UK, Department for International Development, UK Government, European Commission, National Research Foundation, South African Medical Research Council, Poliomyelitis Research Foundation, Department of Science and Technology, Ministry of Science and Technology, India, Department for International Development, National Treasury, Foreign, Commonwealth and Development Office, Global Challenges Research Fund, HORIZON EUROPE Framework Programme, Medical Research Council, Division of Research Capacity Development, European and Developing Countries Clinical Trials Partnership, Wellcome Centre for Infectious Diseases Research in Africa
Awards: Optimising pharmacometric assessment in phase 2 studies of Chagas disease, G1288721568, G1756716151, G2192728021, G2309718249, G2347075150, G2680277565, G2697327848, G3298528487, G3803155102, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), GCRF-Crick African Network, G4040994733, Adaptive responses to SARS-CoV-2 variants in the context of hybrid immunity and immune impairment, G4250852887, LEVERAGING CESGA TO RESEARCH CENTER OF EXCELLENCE, G434337789, G4684020916, EU-Africa Concerted Action on SAR-CoV-2 Virus Variant and Immunological Surveillance, G5446106954, G5449198269, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), G5989569716, G603494317, L. Zuhlke, University of Cape Town: Etiological, intervention and outcome studies in African children, adolescents and young adults with heart disease, G6439542666, G6519211674, G7063735130, G7210099979, G7364435899, G790109484, G790229736, G8578690616, G889251711, G916382336
OpenAlex ID: W4390081084