{"id":114542,"date":"2018-03-11T10:42:36","date_gmt":"2018-03-11T10:42:36","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/monitorizacion-inmunologica-en-trasplante-cardiaco\/"},"modified":"2018-03-11T10:42:36","modified_gmt":"2018-03-11T10:42:36","slug":"monitorizacion-inmunologica-en-trasplante-cardiaco","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/inmunologia\/monitorizacion-inmunologica-en-trasplante-cardiaco\/","title":{"rendered":"Monitorizaci\u00f3n inmunol\u00f3gica en trasplante cardiaco"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Rosa Mar\u00eda Blanco Garcia <\/strong><\/h2>\n<p>Resumen  introducci\u00f3n: \tel trasplante cardiaco es la principal opci\u00f3n terap\u00e9utica en insuficiencia cardiaca terminal. Sin embargo, la inmunosupresi\u00f3n utilizada para evitar el rechazo puede favorecer las infecciones y neoplasias. Por tanto, es necesario disponer de biomarcadores que permitan valorar el estatus inmunitario de cada paciente y as\u00ed ajustar la terapia inmunosupresora a sus caracter\u00edsticas y situaci\u00f3n cl\u00ednica. objetivos: \tel objetivo general propuesto en esta memoria es monitorizar en sangre perif\u00e9rica biomarcadores que permitan evaluar el estatus inmunol\u00f3gico del paciente, antes y despu\u00e9s del trasplante cardiaco, y su relaci\u00f3n con la patolog\u00eda de base (cardiopat\u00eda isqu\u00e9mica y no-isqu\u00e9mica), la frecuencia del rechazo celular agudo, la severidad del rechazo cr\u00f3nico (evaluado mediante ultrasonido intravascular) y la frecuencia y el tipo de infecciones. De entre los objetivos espec\u00edficos destacamos: 1) analizar y cuantificar las principales subpoblaciones leucocitarias (leucocitos, monocitos y neutr\u00f3filos) y linfocitarias (linfocitos t, b y nk), as\u00ed como algunas mol\u00e9culas relacionadas con su activaci\u00f3n y funci\u00f3n (cd80, cd86 y cd95); 2) evaluar la expresi\u00f3n de cd28 y la de receptores kir (kir2dl1\/s1 y kir2dl2\/l3\/s2) en linfocitos t cd4+ y cd8+, y compararla con la observada en los receptores de trasplante hep\u00e1tico de nuestro centro y 3) evaluar la concentraci\u00f3n de hla-g soluble en suero y su relaci\u00f3n con las infecciones y la evoluci\u00f3n de los injertos cardiacos a largo plazo. metodolog\u00eda: \ten 77 trasplantes cardiacos se monitorizaron biomarcadores para evaluar el estatus inmunol\u00f3gico del paciente, tanto en el periodo pre-trasplante como en diversos tiempos durante el primer a\u00f1o post-trasplante. Se obtuvieron muestras de sangre perif\u00e9rica anticoagulada con edta para analizar poblaciones celulares por citometr\u00eda de flujo y muestras de suero para estudiar la concentraci\u00f3n de hla-g soluble mediante elisa (mediante el kit de shla-g de exbio). En el estudio de citometr\u00eda de flujo se utilizaron combinaciones apropiadas de anticuerpos monoclonales marcados con distintos fluorocromos:  anti-cd45, anti-cd14, anti-cd19, anti-cd3, anti-cd4, anti-cd8, anti-cd28, anti-ctla-4, anti-cd86, anti- cd25, anti-cd94, anti-cd80, anti-cd95, anti-cd158a\/h, anti-cd158b\/j y anti-cd56. los datos fueron recogidos en una base de datos dise\u00f1ada en microsoft accessr y procesados con el paquete estad\u00edstico spss 15.0 para windowsr. Las diferencias se consideraron estad\u00edsticamente significativas para valores de p &lt; 0.05. resultados:  \tel aumento de cd28 en linfocitos t cd4+ se asoci\u00f3 significativamente con la aparici\u00f3n de rechazo agudo, tanto en trasplante cardiaco (p=0.008) como en hep\u00e1tico (p=0.0001). En contraste, el n\u00famero de c\u00e9lulas t cd8+cd28- y cd8+cd28-kir2d+ se expandi\u00f3 de manera significativa despu\u00e9s del trasplante en receptores del grupo de no rechazo agudo, en ambos tipos de trasplantes.  \tel incremento post-trasplante de hla-g soluble se detect\u00f3 espec\u00edficamente en receptores con rechazo cr\u00f3nico no severo.  conclusiones:  \tnuestros resultados apoyan que la expresi\u00f3n de cd28 y la de receptores kir2d en linfocitos t de sangre perif\u00e9rica, son sensores del estado inmunol\u00f3gico de los receptores de injertos de coraz\u00f3n y de h\u00edgado. La sobreexpresi\u00f3n de cd28 en linfocitos t cd4+ y cd8+ en los periodos de mayor frecuencia de rechazo agudo, es indicativa de una alo-respuesta activa, mientras que la acumulaci\u00f3n post-trasplante de c\u00e9lulas t cd8+cd28- y cd8+cd28-kir2d+ se correlaciona con una mejor aceptaci\u00f3n temprana del injerto.  \tel incremento post-trasplante, pero no el nivel pre-trasplante, de shla-g se relaciona directamente con protecci\u00f3n frente a rechazo cr\u00f3nico severo.  \tincrementos post-trasplante de la intensidad media de fluorescencia de cd28 sobre linfocitos t cd4+ de sangre perif\u00e9rica superiores al 5%, y de shla-g en suero superiores al 0.062%, respecto a sus valores pre-trasplante, se han establecido como biomarcadores de utilidad cl\u00ednica, con capacidad predictiva de rechazo agudo y cr\u00f3nico (rechazo cr\u00f3nico menos severo), respectivamente.  summary  introduction: \t\theart transplantation is the main treatment option for end-stage heart failure patients. However, immunosuppressive drugs, used in order to prevent graft rejection, may cause infections and malignancies. Therefore, it is necessary to have biomarkers to assess the immune status of each patient and then adjust the immunosuppressive therapy to their characteristics and clinical status. objectives: \tthe main aim of this study was to monitor peripheral blood biomarkers in order to evaluate the patients immune status before and after heart transplantation and its relationship with the underlying pathology (ischemic and non-ischemic heart disease), the frequency of acute cellular rejection, the severity of the chronic rejection (assessed by intravascular ultrasound), and the frequency and type of infections. The specific objectives of this study were: 1) to analyze and quantify the major leukocyte (leukocytes, monocytes and neutrophils) and lymphocyte (t, b and nk) subpopulations, as well as other molecules related to their function and activation (cd80, cd86 and cd95); 2) to evaluate the expression of cd28 and kir receptors (kir2dl1\/s1 and kir2dl2\/l3\/s2) in lymphocytes t, cd4+ and cd8+, and to compare it with that observed in liver transplant recipients from our center and 3) to evaluate the concentration of soluble hla-g in serum and its relationship with infections and the development of long-term cardiac grafts.  methods: \tbiomarkers were monitored in 77 patients with heart transplants in order to evaluate immune status, both in the pre-transplant and at different times during the first year post-transplant. Peripheral blood samples were collected into edta anticoagulated tubes to analyze cell populations by flow cytometry and serum samples were used to study the concentration of soluble hla-g by elisa (using the exbio shla-g kit). Appropriate combinations of monoclonal antibodies labelled with different fluorochromes were used in the flow cytometry study: anti-cd45, anti-cd14, anti-cd19, anti-cd3, anti-cd4, anti-cd8, anti-cd28, anti-ctla-4, anti-cd86, anti- cd25, anti-cd94, anti-cd80, anti-cd95, anti-cd158a\/h, anti-cd158b\/j y anti-cd56. \tthe data were gathered in a microsoft accessr database and processed using spss 15.0 for windowsr.  P-values &lt;0.05 were considered statistically significant.  results:   the increase of cd28 on cd4+ t lymphocytes was significantly associated with the development of acute rejection, both in heart (p = 0.008) and liver (p = 0.0001) transplantation. On the contrary, the number of cd8+cd28- and cd8+cd28-kir2d+ cells expanded significantly after transplantation in the recipient group without acute rejection, in both types of transplantation.  \tan increase in post-transplant soluble hla-g was detected particularly in recipients with chronic but not severe rejection.  conclusions:  \tour results confirm that the expression of cd28 and kir2d receptors on peripheral blood t lymphocytes of heart and liver transplants recipients act as sensors of the immune system status. The up-regulation of cd28 on cd4+ lymphocytes during periods of higher frequency of cellular acute rejection indicates an active allo-response, whilst the post-transplant accumulation of circulating cd8+cd28- and cd8+cd28-kir2d+ t cells correlate with better early graft acceptance.  \tthe post-transplant increase, not the pre-transplantation level, of shla-g is directly related to a protection against severe chronic rejection  \t post-transplant increases in the mfi of cd28 on cd4+ t lymphocytes from peripheral blood by over 5%, and shla-g in serum above 0.062%, compared to values pre-transplantation, have been established as biomarkers able to predict acute and chronic rejection (chronic rejection being less severe), respectively.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Monitorizaci\u00f3n inmunol\u00f3gica en trasplante cardiaco<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Monitorizaci\u00f3n inmunol\u00f3gica en trasplante cardiaco <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Rosa Mar\u00eda Blanco Garcia <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 19\/07\/2013<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Roc\u00edo \u00e1lvarez L\u00f3pez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Mar\u00eda del pilar Garc\u00eda pe\u00f1arrubia <\/li>\n<li>domingo Andr\u00e9s Pascual figal (vocal)<\/li>\n<li>Manuel Muro amador (vocal)<\/li>\n<li>Luisa Mar\u00eda Villar guimerans (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Rosa Mar\u00eda Blanco Garcia Resumen introducci\u00f3n: el trasplante cardiaco es la principal opci\u00f3n terap\u00e9utica en insuficiencia cardiaca [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","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":"","adv-header-id-meta":"","stick-header-meta":"","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":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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