IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort. Spracklen, T. F, Mendelsohn, S. C, Butters, C., Facey-Thomas, H., Stander, R., Abrahams, D., Erasmus, M., Baguma, R., Day, J., Scott, C., Zühlke, L. J, Kassiotis, G., Scriba, T. J, & Webb, K. Frontiers in Immunology, 13:992022, Frontiers, 2022. doi abstract bibtex Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There are 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. Methods: The 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. Results: A 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. Conclusions: These 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.
@article{Spracklen2022,
abstract = {Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There are 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. Methods: The 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. Results: A 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. Conclusions: These 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.},
author = {Spracklen, Timothy F and Mendelsohn, Simon C and Butters, Claire and Facey-Thomas, Heidi and Stander, Raphaella and Abrahams, Debbie and Erasmus, Mzwandile and Baguma, Richard and Day, Jonathan and Scott, Christiaan and Z{\"{u}}hlke, Liesl J and Kassiotis, George and Scriba, Thomas J and Webb, Kate},
doi = {10.3389/FIMMU.2022.992022},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Spracklen et al. - 2022 - IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a Sou.pdf:pdf},
issn = {1664-3224},
journal = {Frontiers in Immunology},
keywords = {COVID - 19,Children,Multisystem inflammatory syndrome,OA,SARS-CoV-2,South Africa,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
pages = {992022},
publisher = {Frontiers},
title = {{IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort}},
volume = {13},
year = {2022}
}
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Methods: The 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. Results: A 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. Conclusions: These 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.","author":[{"propositions":[],"lastnames":["Spracklen"],"firstnames":["Timothy","F"],"suffixes":[]},{"propositions":[],"lastnames":["Mendelsohn"],"firstnames":["Simon","C"],"suffixes":[]},{"propositions":[],"lastnames":["Butters"],"firstnames":["Claire"],"suffixes":[]},{"propositions":[],"lastnames":["Facey-Thomas"],"firstnames":["Heidi"],"suffixes":[]},{"propositions":[],"lastnames":["Stander"],"firstnames":["Raphaella"],"suffixes":[]},{"propositions":[],"lastnames":["Abrahams"],"firstnames":["Debbie"],"suffixes":[]},{"propositions":[],"lastnames":["Erasmus"],"firstnames":["Mzwandile"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Day"],"firstnames":["Jonathan"],"suffixes":[]},{"propositions":[],"lastnames":["Scott"],"firstnames":["Christiaan"],"suffixes":[]},{"propositions":[],"lastnames":["Zühlke"],"firstnames":["Liesl","J"],"suffixes":[]},{"propositions":[],"lastnames":["Kassiotis"],"firstnames":["George"],"suffixes":[]},{"propositions":[],"lastnames":["Scriba"],"firstnames":["Thomas","J"],"suffixes":[]},{"propositions":[],"lastnames":["Webb"],"firstnames":["Kate"],"suffixes":[]}],"doi":"10.3389/FIMMU.2022.992022","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Spracklen et al. - 2022 - IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a Sou.pdf:pdf","issn":"1664-3224","journal":"Frontiers in Immunology","keywords":"COVID - 19,Children,Multisystem inflammatory syndrome,OA,SARS-CoV-2,South Africa,fund_ack,original","mendeley-tags":"OA,fund_ack,original","pages":"992022","publisher":"Frontiers","title":"IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort","volume":"13","year":"2022","bibtex":"@article{Spracklen2022,\r\nabstract = {Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. 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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. Conclusions: These 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. 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