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dc.contributor.authorBermejo-Martin, Jesus F
dc.contributor.authorMartin-Loeches, Ignacio
dc.contributor.authorRello, Jordi
dc.contributor.authorAntón, Andrés
dc.contributor.authorAlmansa, Raquel
dc.contributor.authorXu, Luoling
dc.contributor.authorLopez-Campos, Guillermo
dc.contributor.authorPumarola, Tomás
dc.contributor.authorRan, Longsi
dc.contributor.authorRamirez, Paula
dc.contributor.authorBanner, David
dc.contributor.authorCheuk Ng, Derek
dc.contributor.authorSocias, Lorenzo
dc.contributor.authorLoza, Ana
dc.contributor.authorAndaluz, David
dc.contributor.authorMaravi, Enrique
dc.contributor.authorGómez-Sánchez, Maria J
dc.contributor.authorGordón, Mónica
dc.contributor.authorGallegos, Maria C
dc.contributor.authorFernandez, Victoria
dc.contributor.authorAldunate, Sara
dc.contributor.authorLeón, Cristobal
dc.contributor.authorMerino, Pedro
dc.contributor.authorBlanco, Jesús
dc.contributor.authorMartin-Sanchez, Fernando 
dc.contributor.authorRico, Lucia
dc.contributor.authorVarillas, David
dc.contributor.authorIglesias, Veronica
dc.contributor.authorMarcos, Maria Ángeles
dc.contributor.authorGandía, Francisco
dc.contributor.authorBobillo, Felipe
dc.contributor.authorNogueira, Begoña
dc.contributor.authorRojo, Silvia
dc.contributor.authorResino, Salvador 
dc.contributor.authorCastro, Carmen
dc.contributor.authorOrtiz de Lejarazu, Raul
dc.contributor.authorKelvin, David
dc.date.accessioned2017-09-04T16:26:57Z
dc.date.available2017-09-04T16:26:57Z
dc.date.issued2010-09-14
dc.identifier.citationCrit Care. 2010; 14(5): R167
dc.identifier.urihttp://hdl.handle.net/20.500.12105/4803
dc.description.abstractINTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.
dc.description.sponsorshipThe study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigación Comisionada en Gripe, GR09/0021-EMER07/050- PI081236-RD07/0067. CIHR-NIH-Sardinia Recherché-LKSF Canada support DJK.
dc.language.isoeng
dc.publisherBioMed Central (BMC) 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleHost adaptive immunity deficiency in severe pandemic influenza
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID20840779
dc.format.volume14
dc.format.number5
dc.format.pageR167
dc.identifier.doi10.1186/cc9259
dc.contributor.funderSociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias
dc.contributor.funderCanadian Institutes of Health Research 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderJunta de Castilla y León (España) 
dc.contributor.funderInstituto de Estudios de Ciencias de la Salud de Castilla y León 
dc.description.peerreviewed
dc.identifier.e-issn1364-8535
dc.relation.publisherversionhttps://doi.org/10.1186/cc9259
dc.identifier.journalCritical Care
dc.repisalud.centroISCIII::Centro Nacional de Microbiología
dc.repisalud.institucionISCIII
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional