Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency

[eng] The proper function of the immune system requires complex regulatory mechanisms and a highly strict balance in the amount and function of immune and non-immune elements. Part of the primary immunodeficiencies result from mutations in specific genes and their clinical manifestations can be reca...

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Detalhes bibliográficos
Autor: Rodríguez Cortez, Virginia Carolina
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/67207
Acesso em linha:https://hdl.handle.net/2445/67207
http://hdl.handle.net/10803/311631
Access Level:acceso abierto
Palavra-chave:Immunodeficiència
Epigènesi
Immunodeficiency
Epigenesis
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spelling Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable ImmunodeficiencyRodríguez Cortez, Virginia CarolinaImmunodeficiènciaEpigènesiImmunodeficiencyEpigenesis[eng] The proper function of the immune system requires complex regulatory mechanisms and a highly strict balance in the amount and function of immune and non-immune elements. Part of the primary immunodeficiencies result from mutations in specific genes and their clinical manifestations can be recapitulated through the generation of knockout mice models that support the role of these genes. However, an important number of these disorders cannot be explained by genetic alterations and, to date, there is not an alternative explanation to understand it. This makes difficult the diagnosis process, the establishment of prognosis markers and complicates the finding of specific treatments or the improvement of the existing ones. Epigenetic mechanisms, mainly DNA methylation and histone modifications, are elements of gene control and have emerged to provide explanation to a wide variety of diseases including those related to the immune system. For that reason, this doctoral thesis was focused on investigating the influence of the epigenetic mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency. This was achieved by the establishment of the following specific objectives: 1. To investigate the influence of activation-induced cytidine deaminase (AID), commonly mutated in Hyper-IgM Syndrome, in the setting of epigenetic modifications in an inducible B cell model. 2. To analyze the effects of AID mutations in the acquisition of epigenetic alterations. 3. To determine the participation of epigenetic alterations in CVID by focusing on the DNA methylation profiling of B cells isolated from monozygotic twins discordant for CVID. 4. To expand the results obtained with monozygotic twins discordant for CVID in three different B cell subsets from a cohort of healthy donors and CVID patients.Universitat de BarcelonaBallestar Tarín, EstebanUniversitat de Barcelona. Facultat de Medicina2015info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/67207http://hdl.handle.net/10803/311631Tesis Doctorals - Facultat - Medicinareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Rodríguez, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/672072026-05-27T06:46:51Z
dc.title.none.fl_str_mv Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
title Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
spellingShingle Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
Rodríguez Cortez, Virginia Carolina
Immunodeficiència
Epigènesi
Immunodeficiency
Epigenesis
title_short Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
title_full Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
title_fullStr Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
title_full_unstemmed Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
title_sort Epigenetic Mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency
dc.creator.none.fl_str_mv Rodríguez Cortez, Virginia Carolina
author Rodríguez Cortez, Virginia Carolina
author_facet Rodríguez Cortez, Virginia Carolina
author_role author
dc.contributor.none.fl_str_mv Ballestar Tarín, Esteban
Universitat de Barcelona. Facultat de Medicina
dc.subject.none.fl_str_mv Immunodeficiència
Epigènesi
Immunodeficiency
Epigenesis
topic Immunodeficiència
Epigènesi
Immunodeficiency
Epigenesis
description [eng] The proper function of the immune system requires complex regulatory mechanisms and a highly strict balance in the amount and function of immune and non-immune elements. Part of the primary immunodeficiencies result from mutations in specific genes and their clinical manifestations can be recapitulated through the generation of knockout mice models that support the role of these genes. However, an important number of these disorders cannot be explained by genetic alterations and, to date, there is not an alternative explanation to understand it. This makes difficult the diagnosis process, the establishment of prognosis markers and complicates the finding of specific treatments or the improvement of the existing ones. Epigenetic mechanisms, mainly DNA methylation and histone modifications, are elements of gene control and have emerged to provide explanation to a wide variety of diseases including those related to the immune system. For that reason, this doctoral thesis was focused on investigating the influence of the epigenetic mechanisms in two primary immunodeficiencies: Hyper-IgM Syndrome and Common Variable Immunodeficiency. This was achieved by the establishment of the following specific objectives: 1. To investigate the influence of activation-induced cytidine deaminase (AID), commonly mutated in Hyper-IgM Syndrome, in the setting of epigenetic modifications in an inducible B cell model. 2. To analyze the effects of AID mutations in the acquisition of epigenetic alterations. 3. To determine the participation of epigenetic alterations in CVID by focusing on the DNA methylation profiling of B cells isolated from monozygotic twins discordant for CVID. 4. To expand the results obtained with monozygotic twins discordant for CVID in three different B cell subsets from a cohort of healthy donors and CVID patients.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/67207
http://hdl.handle.net/10803/311631
url https://hdl.handle.net/2445/67207
http://hdl.handle.net/10803/311631
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Rodríguez, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rodríguez, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Medicina
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410163619790849
score 15,301603

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