Investigadors del Grup de Cromatina i Malaltia de l’Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) i de l’Hospital la Paz (IDIPAZ) han identificat per primera vegada alteracions epigen\u00e8tiques en Immunodefici\u00e8ncia Comuna Variable (CVID), la immunodefici\u00e8ncia prim\u00e0ria m\u00e9s freq\u00fcent, utilitzant com a punt de partida bessons monozig\u00f2tics, exactament iguals des del punt de vista gen\u00e8tic, per\u00f2 discordants per a aquesta malaltia. <\/p>\n
La CVID \u00e9s un trastorn caracteritzat per nivells baixos d’anticossos (immunoglobulines del s\u00e8rum) i una major susceptibilitat a infeccions. Les caracter\u00edstiques inicials de la majoria dels pacients amb CVID s\u00f3n infeccions recurrents que involucren orelles, sins paranasals, nas, bronquis i pulmons. Quan les infeccions en pulm\u00f3 s\u00f3n greus i ocorren repetidament, poden ocasionar dany permanent en els bronquis i afectar de manera cr\u00f2nica. <\/p>\n
La causa exacta dels nivells baixos d’immunoglobulines del s\u00e8rum no \u00e9s coneguda. Donada la naturalesa poc uniforme de la CVID, no s’ha definit un patr\u00f3 d’her\u00e8ncia clar, encara que en els \u00faltims anys s’han descrit mutacions en diversos gens relacionats amb la biologia dels limf\u00f2cits en pacients de CVID. Tanmateix, no tots els pacients tenen mutacions identificades i sembla que hi ha altres mecanismes que determinen l’aparici\u00f3 de la malaltia; de fet hi ha exemples de bessons, que comparteixen la mateixa gen\u00e8tica i que, no obstant aix\u00f2, posseeixen diferents graus de manifestaci\u00f3 de la malaltia. <\/p>\n
En aquest estudi, publicat aquesta setmana a la revista Nature Communications<\/em>, i dirigit pels doctors Esteban Ballestar (IDIBELL) i Eduardo Lopez-Granados (IDIPAZ), la comparaci\u00f3 dels patrons epigen\u00e8tics en limf\u00f2cits B d’una parella de bessons id\u00e8ntics, encara que discordants per aquesta malaltia, ha perm\u00e8s identificar l’exist\u00e8ncia d’alteracions epigen\u00e8tiques al bess\u00f3 amb la immunodefici\u00e8ncia que no estan presents al bess\u00f3 sa. En concret es van observar nivells m\u00e9s alts de metilaci\u00f3 de DNA al bess\u00f3 amb CVID. La metilaci\u00f3 de DNA est\u00e0 relacionada amb la capacitat de les c\u00e8l\u00b7lules de permetre que s’expressin els seus gens. <\/p>\n L’an\u00e0lisi va permetre la identificaci\u00f3 d’un grup de gens, importants per al correcte funcionament dels limf\u00f2cits B, que estaven m\u00e9s metilats al bess\u00f3 amb CVID. Posteriorment, es van investigar els mateixos gens en una s\u00e8rie m\u00e9s \u00e0mplia d’individus amb CVID, i es va comparar amb una s\u00e8rie d’individus sans. L’an\u00e0lisi de la metilaci\u00f3 d’aquests gens en limf\u00f2cits en diferents estats de maduraci\u00f3, va mostrar que els pacients de CVID han perdut parcialment la capacitat de desmetilar aquests gens durant el proc\u00e9s de generar limf\u00f2cits madurs. Aquests resultats indiquen que els pacients de CVID no nom\u00e9s produeixen menys limf\u00f2cits B de mem\u00f2ria (la forma madura que produeix anticossos) sin\u00f3 que aquests limf\u00f2cits estan alterats i no han completat b\u00e9 la seva maduraci\u00f3. <\/p>\n Els resultats de l’estudi s\u00f3n la primera evid\u00e8ncia d’aquest tipus d’alteracions epigen\u00e8tiques en el camp de les immunodefici\u00e8ncies prim\u00e0ries i obren la porta a futures vies d’investigaci\u00f3 per al tractament i diagn\u00f2stic de pacients de CVID. <\/p>\n En l’estudi han col\u00b7laborat tamb\u00e9 investigadors i cl\u00ednics del Karolinska Institut<\/em> d’Estocolm i de l’Hospital Son Espases de Palma de Mallorca. <\/p>\n Virginia C. Rodr\u00edguez-Cortez, Lucia del Pino-Molina, Javier Rodr\u00edguez-Ubreva, Laura Ciudad, David G\u00f3mez-Cabrero, Carlos Company, Jos\u00e9 M. Urquiza, Jesper Tegn\u00e9r, Carlos Rodr\u00edguez-Gallego, Eduardo L\u00f3pez-Granados and Esteban Ballestar (2015) Monozygotic Twins Discordant for Common Variable Immunodeficiency Reveal Impaired DNA Demethylation during Na\u00efve-to-Memory B-Cell Transition, Nature Communications, DOI: 10.1038\/ncomms8335.<\/p>\n","protected":false},"excerpt":{"rendered":" Refer\u00e8ncia:<\/p>\n","protected":false},"author":6,"featured_media":10883,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-11 13:43:46","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8133"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8133"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8133\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/10883"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8133"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8133"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8133"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}