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IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

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posted on 2022-09-09, 09:44 authored by Timothy F Spracklen, Simon C Mendelsohn, Claire Butters, Heidi Facey-Thomas, Raphaella Stander, Debbie Abrahams, Mzwandile Erasmus, Richard Baguma, Jonathan Day, Christiaan Scott, Liesl J Zühlke, George Kassiotis, Thomas J Scriba, Kate Webb
Introduction: Multisystem 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. 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.


Medical Research Council (Grant ID: MR/P028071/1, Grant title: GCRF-Crick African Network) Crick (Grant ID: 10099, Grant title: Kassiotis FC001099)


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