tetano
Editor, Senior Moderator
Clin Immunol
. 2023 Dec 21:109877.
doi: 10.1016/j.clim.2023.109877. Online ahead of print. 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
Claire Butters[SUP] 1 [/SUP], Ntombi Benede[SUP] 2 [/SUP], Thandeka Moyo-Gwete[SUP] 3 [/SUP], Simone I Richardson[SUP] 4 [/SUP], Ursula Rohlwink[SUP] 5 [/SUP], Muki Shey[SUP] 6 [/SUP], Frances Ayres[SUP] 7 [/SUP], Nelia P Manamela[SUP] 8 [/SUP], Zanele Makhado[SUP] 9 [/SUP], Sashkia R Balla[SUP] 10 [/SUP], Mashudu Madzivhandila[SUP] 9 [/SUP], Amkele Ngomti[SUP] 11 [/SUP], Richard Baguma[SUP] 12 [/SUP], Heidi Facey-Thomas[SUP] 13 [/SUP], Timothy F Spracklen[SUP] 14 [/SUP], Jonathan Day[SUP] 15 [/SUP], Hamza van der Ross Debbie[SUP] 16 [/SUP], Catherine Riou[SUP] 17 [/SUP], Wendy A Burgers[SUP] 18 [/SUP], Christiaan Scott[SUP] 19 [/SUP], Liesl Zuhlke[SUP] 20 [/SUP], Penny L Moore[SUP] 21 [/SUP], Roanne S Keeton[SUP] 22 [/SUP], Kate Webb[SUP] 23 [/SUP]
Affiliations
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.
Keywords: Antibody effector function; Inflammatory cytokine profile; MIS-C; SARS-CoV-2-specific T cells.
. 2023 Dec 21:109877.
doi: 10.1016/j.clim.2023.109877. Online ahead of print. 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
Claire Butters[SUP] 1 [/SUP], Ntombi Benede[SUP] 2 [/SUP], Thandeka Moyo-Gwete[SUP] 3 [/SUP], Simone I Richardson[SUP] 4 [/SUP], Ursula Rohlwink[SUP] 5 [/SUP], Muki Shey[SUP] 6 [/SUP], Frances Ayres[SUP] 7 [/SUP], Nelia P Manamela[SUP] 8 [/SUP], Zanele Makhado[SUP] 9 [/SUP], Sashkia R Balla[SUP] 10 [/SUP], Mashudu Madzivhandila[SUP] 9 [/SUP], Amkele Ngomti[SUP] 11 [/SUP], Richard Baguma[SUP] 12 [/SUP], Heidi Facey-Thomas[SUP] 13 [/SUP], Timothy F Spracklen[SUP] 14 [/SUP], Jonathan Day[SUP] 15 [/SUP], Hamza van der Ross Debbie[SUP] 16 [/SUP], Catherine Riou[SUP] 17 [/SUP], Wendy A Burgers[SUP] 18 [/SUP], Christiaan Scott[SUP] 19 [/SUP], Liesl Zuhlke[SUP] 20 [/SUP], Penny L Moore[SUP] 21 [/SUP], Roanne S Keeton[SUP] 22 [/SUP], Kate Webb[SUP] 23 [/SUP]
Affiliations
- PMID: 38141746
- DOI: 10.1016/j.clim.2023.109877
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.
Keywords: Antibody effector function; Inflammatory cytokine profile; MIS-C; SARS-CoV-2-specific T cells.