Transcriptomics

Dataset Information

16

Hosts responses in critical disease caused by pandemic H1N1


ABSTRACT: Critical disease caused by the new 2009 pandemic influenza virus (nvH1N1) is a challenge for physicians and scientist. As evidenced in SARS and H5N1, the development of an effective immune response plays a key role to overcome viral diseases. We studied host`s gene expression signatures, cytokine and antibody responses along the first week of hospitalization in 19 critically ill patients with primary nvH1N1 pneumonia and two degrees of respiratory involvement. Presence of comorbidities and absence of immunosuppresory conditions were the common antecedents in both groups. The most severe patients (n=12) showed persistant respiratory viral secretion, increased levels of pro-inflammatory cytokines and chemokines in serum, and elevated systemic levels of two immunosuppresory cytokines (IL-10 and IL-1ra). Both groups were able to produce specific antibodies against the virus. The average day for antibody production was day 9 in the course of the disease, defining an early period of innate immunity and a late period of adaptive immunity. The most severe group evidenced a poor expression of a set of MHC class II and T cell receptor (TCR) related genes participating in antigen presentation and cell mediated immune responses in the late phase. 7 patients of this group finally died. This findings evidence that, as observed in sepsis, severe H1N1 disease course with immunoparalysis, which could explain the poor control of the virus along with the increased incidence of bacterial superinfection observed in these patients. 19 patients attending to the participants ICUs with primary viral pneumonia during the acute phase of influenza virus illness with acute respiratory distress and unequivocal alveolar opacification involving two or more lobes with negative respiratory and blood bacterial cultures at admission were recruited from November the 1st to December the 31st 2009. Serial blood samples for plasma, serum and RNA were collected by using Serum, EDTA and PaxGene (BD®) venous blood vacuum collection following manufacturer instructions at day 1, 3/5 and 7 according to an unified protocol for all the participant ICUs. A pharyngeal sample was collected in paralel. RNA from blood was processed for gene expression analysis by using Sentrix Human-6 v2 Expression BeadChips (Illumina, San Diego, CA). RNA from blood obtained from 4 healthy controls was used for comparison purposes. Samples were distributed in four groups depending on whether or not the patients nedeed of mechanical ventilation, and on the early/late phase of the disease (before or after day 9 respectively).

ORGANISM(S): Homo sapiens  

SUBMITTER: Longsi Ran   David J Kelvin 

PROVIDER: E-GEOD-21802 | ArrayExpress | 2011-05-05

SECONDARY ACCESSION(S): GSE21802PRJNA126957

REPOSITORIES: GEO, ArrayExpress

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Publications

Host adaptive immunity deficiency in severe pandemic influenza.

Bermejo-Martin Jesus F JF   Martin-Loeches Ignacio I   Rello Jordi J   Antón Andres A   Almansa Raquel R   Xu Luoling L   Lopez-Campos Guillermo G   Pumarola Tomás T   Ran Longsi L   Ramirez Paula P   Banner David D   Ng Derek Cheuk DC   Socias Lorenzo L   Loza Ana A   Andaluz David D   Maravi Enrique E   Gómez-Sánchez Maria J MJ   Gordón Mónica M   Gallegos Maria C MC   Fernandez Victoria V   Aldunate Sara S   León Cristobal C   Merino Pedro P   Blanco Jesús J   Martin-Sanchez Fernando F   Martin-Sanchez Fernando F   Rico Lucia L   Varillas David D   Iglesias Veronica V   Marcos Maria Ángeles MÁ   Gandía Francisco F   Bobillo Felipe F   Nogueira Begoña B   Rojo Silvia S   Resino Salvador S   Castro Carmen C   Ortiz de Lejarazu Raul R   Kelvin David D  

Critical care (London, England) 20100914 5


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.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  ...[more]

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