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

Autor:	Spracklen TF; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Cape Heart Institute, University of Cape Town, Cape Town, South Africa., Mendelsohn SC; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Butters C; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Facey-Thomas H; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Stander R; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Abrahams D; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Erasmus M; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Baguma R; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Day J; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Scott C; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Zühlke LJ; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; South African Medical Research Council, Cape Town, South Africa., Kassiotis G; Retroviral Immunology Laboratory, The Francis Crick Institute, London, United Kingdom.; Department of Infectious Disease, St Mary's Hospital, Imperial College, London, United Kingdom., Scriba TJ; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Webb K; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Crick African Network, The Francis Crick Institute, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 06; Vol. 13, pp. 992022. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.992022
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Spracklen, Mendelsohn, Butters, Facey-Thomas, Stander, Abrahams, Erasmus, Baguma, Day, Scott, Zühlke, Kassiotis, Scriba and Webb.)
Databáze:	MEDLINE
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