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Repisalud author Bermejo-Martin, Jesús F author Martin-Loeches, Ignacio author Rello, Jordi author Antón, Andrés author Almansa, Raquel author Xu, Luoling author Lopez-Campos, Guillermo author Pumarola, Tomas author Ran, Longsi author Ramirez, Paula author Banner, David author Cheuk Ng, Derek author Socias, Lorenzo author Loza, Ana author Andaluz, David author Maravi, Enrique author Gómez-Sánchez, Maria J author Gordón, Mónica author Gallegos, Maria C author Fernandez, Victoria author Aldunate, Sara author León, Cristobal author Merino, Pedro author Blanco, Jesús author Martin-Sanchez, Fernando author Rico, Lucía author Varillas, David author Iglesias, Verónica author Marcos, María Ángeles author Gandía, Francisco author Bobillo, Felipe author Nogueira, Begoña author Rojo, Silvia author Resino, Salvador author Castro, Carmen author Ortíz de Lejarazu, Raúl author Kelvin, David funder Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias funder Canadian Institutes of Health Research funder Ministerio de Economía y Competitividad (España) funder Instituto de Salud Carlos III funder Junta de Castilla y León (España) funder Instituto de Estudios de Ciencias de la Salud de Castilla y León 2017-09-04T16:26:57Z 2017-09-04T16:26:57Z 2010-09-14 Crit Care. 2010; 14(5): R167 10.1186/cc9259 1364-8535 Critical Care 20840779 http://hdl.handle.net/20.500.12105/4803 INTRODUCTION: 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. eng Host adaptive immunity deficiency in severe pandemic influenza research article URL https://repisalud.isciii.es/bitstreams/5287d4fd-c51f-4b0e-b6fe-5a8b1db98f3b/download File MD5 d4bf24a53e2ac436e9a9ceb700d838be 1439892 application/pdf HostAdaptiveImmunityDeficiency_2010.pdf URL https://repisalud.isciii.es/bitstreams/f73cb6ba-d31c-4b30-bb53-18502c1215b7/download File MD5 98d09e8a2747db538b3857e20d9dd893 50541 text/plain 13054_2010_Article_8656.pdf.txt URL https://repisalud.isciii.es/bitstreams/089d6027-0259-4d05-8532-40a7739ff259/download File MD5 98d09e8a2747db538b3857e20d9dd893 50541 text/plain HostAdaptiveImmunityDeficiency_2010.pdf.txt URL https://repisalud.isciii.es/bitstreams/dc779877-3cc6-4451-be7b-040f46f0b18a/download File MD5 98d09e8a2747db538b3857e20d9dd893 50541 text/plain HostAdaptiveImmunityDeficiency_2010.pdf.txt