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Peripheral blood cells expression data form 7 patients with severe pdm(H1N1) influensa and 7 gender and age matched healthy controls

ABSTRACT: Using PAXgene tubes, peripheral blood samples were collected from seven patients >18 years with documented pdm(H1N1) influenza, bilateral chest infiltrates, and in need of ventilation support. Significant co-morbidity was exclusion criterion. Expression profiles were compared with 7 age matched controls. Using a false discovery rate < 5% and an absolute fold change > 2, 370 genes were differentially expressed in case and controls. A second sample was collected after ca 6 days in the 7 patients and temporal changes in expression profiles investigated. Over expressed putative mediators of inflammatory lung dammage were measured on the protein level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27131 | GEO | 2011/04/01

SECONDARY ACCESSION(S): PRJNA137417

REPOSITORIES: GEO

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Project description: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).

Project description:In this model of ventilator-induced lung injury (VILI), we compared the gene expression profile of whole lungs extracted from sponaneously breathing mice (control, c) or mouse submitted to 8 hours mechanical venitlation with 12 ml/kg tidal volume 2cmH2O of positive end expiratory pressure (PEEP) (ventilation, v). Spontaneously breathing NOD/shi mice were randomized to control (n=3) or ventilation (n=5) condition. In brief, mice were anesthetized with the injection of ketamine (65 mg/kg, ip), acepromazine (2 mg/kg, ip) and xylazine (13 mg/kg, ip)(Henry Schein Inc., Melville, NY). Once deep sedation was achieved, a tracheostomy was performed and a PE-10 cannula was inserted in the trachea and stabilized with silk ligature. Control animals were immediately sacrificied with a supra-physiological dose of ketamine (300 mg/kg, ip). For ventilated mice, the cannula was connected to a custom built Voltek rodent ventilator (Voltek Enterprises, Toronto, CA). We ventilated mice for 8 hours using 2cmH2O positive end expiratory pressure (PEEP), inflating the lungs every hour to 20 cmH2O pressure as we have previously described. (16). The chest muscle was paralyzed with the injection of pancurorium (1mg/kg, ip)(Sigma-Aldrich) in ventilated mice to avoid spontaneous breathing. Heart rate and respiratory rate was continuously monitored and additional anesthesia was provided if a >15% increase in these parameters was detected. The animal protocol was approved by the BWH Institutional Animal Care and Use Committee (protocol #04477). Ventilated animals At the end of the each experiment, the animals were sacrificed with a supra-physiological dose of ketamine (300 mg/kg, ip). Subsequently, the chest cavity was opened, and the right lung was isolated and ligated at the main bronchus.Lungs were harvested and snap frozen in liquid nitrogen for total RNA extraction. Total RNA was extracted from lungs of controls (n=3) and mice submitted to ventilation (n=5) and there gene expression profiles were compared.

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Peripheral blood cells expression data form 7 patients with severe pdm(H1N1) influensa and 7 gender and age matched healthy controls

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