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| Status |
Public on May 05, 2011 |
| Title |
Hosts responses in critical disease caused by pandemic H1N1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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).
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| Contributor(s) |
Kelvin DJ |
| Citation(s) |
20840779 |
| Submission date |
May 12, 2010 |
| Last update date |
Feb 15, 2013 |
| Contact name |
Longsi Ran |
| E-mail(s) |
lran@uhnresearch.ca
|
| Phone |
416-581-7607
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| Organization name |
Toronto General Research Institute
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| Department |
Division of Experimental Therapeutics
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| Lab |
Dr. David J Kelvin
|
| Street address |
101 College Street
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| City |
Toronto |
| State/province |
ON |
| ZIP/Postal code |
M5G 1L7 |
| Country |
Canada |
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| Platforms (1) |
| GPL6102 |
Illumina human-6 v2.0 expression beadchip |
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| Samples (40)
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| GSM542944 |
Healthy Control, biological rep4 |
| GSM542945 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep1 |
| GSM542946 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep2 |
| GSM542947 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep3 |
| GSM542948 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep1 |
| GSM542949 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep2 |
| GSM542950 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep1 |
| GSM542951 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep4 |
| GSM542952 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep3 |
| GSM542953 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep1 |
| GSM542954 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep5 |
| GSM542955 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep2 |
| GSM542956 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep3 |
| GSM542957 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep2 |
| GSM542958 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep4 |
| GSM542959 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep4 |
| GSM542960 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep5 |
| GSM542961 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep6 |
| GSM542962 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep6 |
| GSM542963 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep5 |
| GSM542964 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep3 |
| GSM542965 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep7 |
| GSM542966 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep8 |
| GSM542967 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep9 |
| GSM542968 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep7 |
| GSM542969 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep10 |
| GSM542970 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep4 |
| GSM542971 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep8 |
| GSM542972 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep5 |
| GSM542973 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep9 |
| GSM542974 |
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep6 |
| GSM542975 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep6 |
| GSM542976 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep11 |
| GSM542977 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep12 |
| GSM542978 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep13 |
| GSM542979 |
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep14 |
| GSM542980 |
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period,biological rep10 |
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| Relations |
| BioProject |
PRJNA126957 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21802_RAW.tar |
5.8 Mb |
(http)(custom) |
TAR |
| GSE21802_non-normalized_data.txt.gz |
12.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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