Scientists have found specific epigenetic changes present during hyperinflammation in a rare childhood complication of COVID-19, multisystem inflammatory syndrome.
A small number of children who have been infected with SARS-CoV-2 go on to experience a condition called multisystem inflammatory syndrome in children (MIS-C). Over half of these children needed intensive care.
The international research team was led by Dr Manel Esteller at the Josep Carreras Leukaemia Research Institute and Dr Aurora Pujol, from the Bellvitge Biomedical Research Institute in Barcelona, Spain.
The researchers write: “The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C.”
Blood samples were taken from 43 children with MIS-C, which were compared with samples from 15 children with COVID-19 but without MIS-C, and 69 unaffected children. About 850,000 areas of the genome were examined for epigenetic changes called DNA methylation – chemical changes to the DNA molecule which affect gene activity.
The team report that differences were seen in 33 areas between those with MIS-C and those without. Genes involved included the immune T-cell mediator ZEB2, the VWA8 gene which contains a domain of the Von Willebrand factor A, and certain pro-inflammatory genes.
Interestingly, a similar epigenetic signature was also seen in many patients with Kawasaki disease, which may also have a viral trigger – underlining the similarities between the two conditions. “It seems that in both syndromes, MIS-C and Kawasaki, there is an exaggerated reaction of the children's immune system against a viral attack,” Dr Esteller says. “Knowing the mechanisms triggering both diseases will give us better tools to diagnose and treat them”.
The scientists write: “We have characterised DNA methylation loci that are associated with MIS-C diagnosis. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients.
“The described epigenetic signature could also provide new targets for more specific therapies for the disorder.”
The study was published in eClinicalMedicine.
Source: Davalos V, García-Prieto CA, Ferrer G, Aguilera-Albesa S, Valencia-Ramos J, Rodríguez-Palmero A, Ruiz M, Planas-Serra L, Jordan I, Alegría I, Flores-Pérez P, Cantarín V, Fumadó V, Viadero MT, Rodrigo C, Méndez-Hernández M, López-Granados E, Colobran R, Rivière JG, Soler-Palacín P, Pujol A, Esteller M. (2022) “Epigenetic Profiling Linked to Multisystem Inflammatory Syndrome in Children (MIS-C): A Multicenter, Retrospective Study.” eClinicalMedicine, doi: 10.1016/j.eclinm.2022.101515
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