2026-04-17T05:49:41Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1889042025-12-05T09:23:55Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Davalos, Veronica author García Prieto, Carlos Antonio author Ferrer, Gerardo author Aguilera Albesa, Sergio author Valencia Ramos, Juan author Rodríguez Palmero, Agustí author Ruiz, Montserrat author Planas Serra, Laura author Jordán García, Iolanda author Alegría, Iosune author Flores Pérez, Patricia author Cantarín, Verónica author Fumadó, Victoria author Viadero, Maria Teresa author Rodrigo, Carlos author Méndez Hernández, Maria author López Granados, Eduardo author Colobran, Roger author Rivière, Jacques G. author Soler Palacín, Pere author Pujol, Aurora, 1968- author Esteller, Manel author 2022-09-12T10:12:55Z 2022-09-12T10:12:55Z 2022-08-01 2022-08-16T12:57:29Z Background Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, multisystem inflammatory syndrome in children (MIS-C). 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. Methods Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C= 29 and non-MIS-C= 56) and validation (MIS-C= 14 and non-MIS C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation We have characterized 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. COVID-19 Epigenètica Infants Adolescents Teenagers COVID-19 Epigenetics Children Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study