IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort
IntroductionMultisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.992022/full |
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| author | Timothy F. Spracklen Timothy F. Spracklen Simon C. Mendelsohn Claire Butters Claire Butters Heidi Facey-Thomas Raphaella Stander Debbie Abrahams Mzwandile Erasmus Richard Baguma Jonathan Day Christiaan Scott Liesl J. Zühlke Liesl J. Zühlke Liesl J. Zühlke George Kassiotis George Kassiotis Thomas J. Scriba Kate Webb Kate Webb |
| author_facet | Timothy F. Spracklen Timothy F. Spracklen Simon C. Mendelsohn Claire Butters Claire Butters Heidi Facey-Thomas Raphaella Stander Debbie Abrahams Mzwandile Erasmus Richard Baguma Jonathan Day Christiaan Scott Liesl J. Zühlke Liesl J. Zühlke Liesl J. Zühlke George Kassiotis George Kassiotis Thomas J. Scriba Kate Webb Kate Webb |
| author_sort | Timothy F. Spracklen |
| collection | DOAJ |
| description | IntroductionMultisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls.MethodsThe cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR.ResultsA total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity.ConclusionsThese data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting. |
| first_indexed | 2024-12-10T15:20:52Z |
| format | Article |
| id | doaj.art-d7ac4d8646a54854b4af3a86f551f2e7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T15:20:52Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d7ac4d8646a54854b4af3a86f551f2e72022-12-22T01:43:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.992022992022IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohortTimothy F. Spracklen0Timothy F. Spracklen1Simon C. Mendelsohn2Claire Butters3Claire Butters4Heidi Facey-Thomas5Raphaella Stander6Debbie Abrahams7Mzwandile Erasmus8Richard Baguma9Jonathan Day10Christiaan Scott11Liesl J. Zühlke12Liesl J. Zühlke13Liesl J. Zühlke14George Kassiotis15George Kassiotis16Thomas J. Scriba17Kate Webb18Kate Webb19Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaCape Heart Institute, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaCape Heart Institute, University of Cape Town, Cape Town, South AfricaSouth African Medical Research Council, Cape Town, South AfricaRetroviral Immunology Laboratory, The Francis Crick Institute, London, United KingdomDepartment of Infectious Disease, St Mary’s Hospital, Imperial College, London, United KingdomSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaCrick African Network, The Francis Crick Institute, London, United KingdomIntroductionMultisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls.MethodsThe cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR.ResultsA total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity.ConclusionsThese data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting.https://www.frontiersin.org/articles/10.3389/fimmu.2022.992022/fullCOVID-19multisystem inflammatory syndromechildrenSouth AfricaSARS-CoV-2 |
| spellingShingle | Timothy F. Spracklen Timothy F. Spracklen Simon C. Mendelsohn Claire Butters Claire Butters Heidi Facey-Thomas Raphaella Stander Debbie Abrahams Mzwandile Erasmus Richard Baguma Jonathan Day Christiaan Scott Liesl J. Zühlke Liesl J. Zühlke Liesl J. Zühlke George Kassiotis George Kassiotis Thomas J. Scriba Kate Webb Kate Webb IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort Frontiers in Immunology COVID-19 multisystem inflammatory syndrome children South Africa SARS-CoV-2 |
| title | IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort |
| title_full | IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort |
| title_fullStr | IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort |
| title_full_unstemmed | IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort |
| title_short | IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort |
| title_sort | il27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a south african cohort |
| topic | COVID-19 multisystem inflammatory syndrome children South Africa SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.992022/full |
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