Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) : A multicenter, retrospective study
Davalos, Veronica (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
García-Prieto, Carlos A (Barcelona Supercomputing Center)
Ferrer, Gerardo (Centro de Investigación Biomédica en Red de Cáncer)
Aguilera-Albesa, Sergio (Complejo Hospitalario de Navarra)
Valencia-Ramos, Juan (Hospital Universitario de Burgos)
Rodríguez-Palmero, Agustí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ruiz, Montserrat (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Planas-Serra, Laura (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Jordán García, Iolanda (Hospital Sant Joan de Déu (Barcelona, Catalunya))
Alegría, Iosune (Complejo Hospitalario de Navarra)
Flores-Pérez, Patricia (Pediatrics Department. Hospital Universitario Niño Jesús)
Cantarín, Verónica (Pediatrics Department. Hospital Universitario Niño Jesús)
Fumadó, Victoria (Hospital Sant Joan de Déu (Barcelona, Catalunya))
Viadero, Maria Teresa (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Rodrigo, Carlos (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Méndez-Hernández, Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
López-Granados, Eduardo (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Colobrán Oriol, Roger (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rivière, Jacques G.. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Soler-Palacín, Pere (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pujol, Aurora 1968- (Institució Catalana de Recerca i Estudis Avançats)
Esteller, M (Universitat de Barcelona. Departament de Ciències Fisiològiques)
Universitat Autònoma de Barcelona. Departament de Pediatria, d'Obstetrícia i Ginecologia i de Medicina Preventiva

Data:	2022
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Multisystem inflammatory syndrome in children ; COVID-19 ; Kawasaki disease ; Epigenetics ; DNA methylation
Publicat a:	EClinicalMedicine, Vol. 50 (august 2022) , art. 101515, ISSN 2589-5370

DOI: 10.1016/j.eclinm.2022.101515
PMID: 35770252

12 p, 844.6 KB

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