Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C)
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 dev...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:270654 |
| Acesso em linha: | https://ddd.uab.cat/record/270654 https://dx.doi.org/urn:doi:10.1016/j.eclinm.2022.101515 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Multisystem inflammatory syndrome in children COVID-19 Kawasaki disease Epigenetics DNA methylation |
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oai:ddd.uab.cat:270654 |
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España |
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| dc.title.none.fl_str_mv |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) A multicenter, retrospective study |
| title |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| spellingShingle |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) Davalos, Veronica|||0000-0003-4077-5137 Multisystem inflammatory syndrome in children COVID-19 Kawasaki disease Epigenetics DNA methylation |
| title_short |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| title_full |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| title_fullStr |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| title_full_unstemmed |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| title_sort |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C) |
| dc.creator.none.fl_str_mv |
Davalos, Veronica|||0000-0003-4077-5137 García-Prieto, Carlos A.|||0000-0001-5021-6916 Ferrer, Gerardo|||0000-0002-4084-6815 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 Valencia-Ramos, Juan Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Planas-Serra, Laura|||0000-0002-2586-0897 Jordán García, Iolanda|||0000-0002-2041-4425 Alegría, Iosune Flores-Pérez, Patricia|||0000-0003-2321-395X Cantarín, Verónica Fumadó, Victoria Viadero, Maria Teresa Rodrigo Gonzalo de Líria, Carlos|||0000-0003-1140-2585 Méndez-Hernández, Maria López-Granados, Eduardo Colobrán Oriol, Roger|||0000-0002-5964-536X Rivière, Jacques G.|||0000-0003-1055-2063 Soler-Palacín, Pere|||0000-0002-0346-5570 Pujol, Aurora|||0000-0002-9606-0600 Esteller, M.|||0000-0003-4490-6093 |
| author |
Davalos, Veronica|||0000-0003-4077-5137 |
| author_facet |
Davalos, Veronica|||0000-0003-4077-5137 García-Prieto, Carlos A.|||0000-0001-5021-6916 Ferrer, Gerardo|||0000-0002-4084-6815 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 Valencia-Ramos, Juan Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Planas-Serra, Laura|||0000-0002-2586-0897 Jordán García, Iolanda|||0000-0002-2041-4425 Alegría, Iosune Flores-Pérez, Patricia|||0000-0003-2321-395X Cantarín, Verónica Fumadó, Victoria Viadero, Maria Teresa Rodrigo Gonzalo de Líria, Carlos|||0000-0003-1140-2585 Méndez-Hernández, Maria López-Granados, Eduardo Colobrán Oriol, Roger|||0000-0002-5964-536X Rivière, Jacques G.|||0000-0003-1055-2063 Soler-Palacín, Pere|||0000-0002-0346-5570 Pujol, Aurora|||0000-0002-9606-0600 Esteller, M.|||0000-0003-4490-6093 |
| author_role |
author |
| author2 |
García-Prieto, Carlos A.|||0000-0001-5021-6916 Ferrer, Gerardo|||0000-0002-4084-6815 Aguilera-Albesa, Sergio|||0000-0003-3540-1448 Valencia-Ramos, Juan Rodríguez-Palmero, Agustí|||0000-0002-4141-5515 Ruiz, Montserrat|||0000-0003-0466-2653 Planas-Serra, Laura|||0000-0002-2586-0897 Jordán García, Iolanda|||0000-0002-2041-4425 Alegría, Iosune Flores-Pérez, Patricia|||0000-0003-2321-395X Cantarín, Verónica Fumadó, Victoria Viadero, Maria Teresa Rodrigo Gonzalo de Líria, Carlos|||0000-0003-1140-2585 Méndez-Hernández, Maria López-Granados, Eduardo Colobrán Oriol, Roger|||0000-0002-5964-536X Rivière, Jacques G.|||0000-0003-1055-2063 Soler-Palacín, Pere|||0000-0002-0346-5570 Pujol, Aurora|||0000-0002-9606-0600 Esteller, M.|||0000-0003-4490-6093 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona. Departament de Pediatria, d'Obstetrícia i Ginecologia i de Medicina Preventiva |
| dc.subject.none.fl_str_mv |
Multisystem inflammatory syndrome in children COVID-19 Kawasaki disease Epigenetics DNA methylation |
| topic |
Multisystem inflammatory syndrome in children COVID-19 Kawasaki disease Epigenetics DNA methylation |
| description |
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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/270654 https://dx.doi.org/urn:doi:10.1016/j.eclinm.2022.101515 |
| url |
https://ddd.uab.cat/record/270654 https://dx.doi.org/urn:doi:10.1016/j.eclinm.2022.101515 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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|
| _version_ |
1869418513616076800 |
| spelling |
Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C)A multicenter, retrospective studyDavalos, Veronica|||0000-0003-4077-5137García-Prieto, Carlos A.|||0000-0001-5021-6916Ferrer, Gerardo|||0000-0002-4084-6815Aguilera-Albesa, Sergio|||0000-0003-3540-1448Valencia-Ramos, JuanRodríguez-Palmero, Agustí|||0000-0002-4141-5515Ruiz, Montserrat|||0000-0003-0466-2653Planas-Serra, Laura|||0000-0002-2586-0897Jordán García, Iolanda|||0000-0002-2041-4425Alegría, IosuneFlores-Pérez, Patricia|||0000-0003-2321-395XCantarín, VerónicaFumadó, VictoriaViadero, Maria TeresaRodrigo Gonzalo de Líria, Carlos|||0000-0003-1140-2585Méndez-Hernández, MariaLópez-Granados, EduardoColobrán Oriol, Roger|||0000-0002-5964-536XRivière, Jacques G.|||0000-0003-1055-2063Soler-Palacín, Pere|||0000-0002-0346-5570Pujol, Aurora|||0000-0002-9606-0600Esteller, M.|||0000-0003-4490-6093Multisystem inflammatory syndrome in childrenCOVID-19Kawasaki diseaseEpigeneticsDNA methylationBackground: 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.Universitat Autònoma de Barcelona. Departament de Pediatria, d'Obstetrícia i Ginecologia i de Medicina Preventiva 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/270654https://dx.doi.org/urn:doi:10.1016/j.eclinm.2022.101515reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2706542026-06-06T12:50:31Z |
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15,301603 |