La producción de interferón gamma por linfoticos t cd8+ cmv específicos confiere protección frente a la reactivación de citomegalovirus en el paciente crítico

Resumen

1. Motivación de la tesis El citomegalovirus (CMV) es un virus herpes beta tipo 5 con una elevada seroprevalencia en la población general. La mayoría de las primoinfecciones ocurren en la infancia y son asintomáticas, pasando, a continuación, a una fase latente, definida como persistencia del genoma viral en ausencia de producción de viriones infectantes en individuos inmunocompetentes. La fase latente puede dar paso a una reactivación en presencia de estímulos como pueden ser la inmunosupresión o una respuesta inflamatoria intensa. Mediante el empleo de técnicas moleculares como la reacción en cadena de la polimerasa (PCR) se ha podido implicar al CMV como patógeno inesperado incluso en el paciente inmunocompetetente crítico, pudiendo empeorar su pronóstico. En el paciente inmunodeprimido, especialmente en el trasplantado, se ha intentado predecir su reactivación, siendo prometedor el papel de la inmunidad del huésped mediada por linfocitos T CD8+, tanto directamente por su fenotipo como indirectamente midiendo el interferón específico frente a CMV mediante QuantiFERON-CMV®. 2. Contenido de la investigación Hipótesis y Objetivos: Evaluar la utilidad de la determinación de la producción de interferón gamma (IFNγ) por los linfocitos T CD8+ específicos de citomegalovirus (CMV) para determinar el riesgo de reactivación de CMV en el paciente crítico previamente no inmunocomprometido. Material y Método: Cohorte prospectiva reclutada en dos centros hospitalarios constituida por pacientes críticos no inmunocomprometidos seropositivos para CMV que ingresaron en Unidad de Cuidados Intensivos (UCI) entre diciembre de 2012 y marzo de 2013. La incidencia de reactivación de CMV se evaluó mediante reacción en cadena de la polimerasa (PCR) en plasma. Se determinó el nivel de secreción de IFNγ al ingreso en UCI mediante QuantiFERON-CMV (QF-CMV). Se analizaron mediante regresión de Cox los factores asociados a reactivación viral. Resultados: Se incluyeron 53 pacientes, de los cuales 13 (24,5 %) presentaron reactivación de CMV. Veintiséis pacientes (49,1 %) fueron QF-CMV-Reactivo. De esos 26 pacientes, 11,5 % (3/26) presentaron reactivación de CMV frente al 37% (10/27) de los QF-CMV-No reactivo (p=0,03). Mediante regresión de Cox, la presencia de QF-CMV-Reactivo al ingreso en UCI se asoció a un menor riesgo de reactivación de CMV (OR 0,09; IC 95% 0,02-0,44; p=0,003). La sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo del QF-CMV fueron, respectivamente, del 77, 57, 37 y 88%. Once de los pacientes (20,7%) fallecieron durante el período de seguimiento. La mortalidad fue mayor en aquellos pacientes con reactivación de CMV (6/13, 46,1% frente a 5/40, 12,5%; p=0,015). 3. 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