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Clinical

Hosts responses in critical disease caused by pandemic H1N1- GSE21802

Purpose

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.

Hypothesis

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Experimental 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).

Experimental Variables

Influenza virus (H1N1) (2021 ICD-10-CM code* = J10.1)

Controls

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Methods

The data were normalized using quantile normalization with Illumina GenomeStudio_2010.1

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse21802

Microarray
Illumina HumanWG-6 v2
40 Samples Loaded: 40
Human (Homo sapiens)
Whole Blood
Influenza virus (H1N1)
RNA was extracted with PAXgene Blood RNA Kit in accordance with the prescribed protocol provided with the kit.
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title tissue Patient Disease phase Mechanical ventilation
GSM542941 Healthy Control, biological rep1 Blood control control
GSM542942 Healthy Control, biological rep2 Blood control control
GSM542943 Healthy Control, biological rep3 Blood control control
GSM542944 Healthy Control, biological rep4 Blood control control
GSM542945 Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep1 Blood 1 late period no
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File
sampleset4000216_sampleannotations_GSE21802.csv
Sample Set Spreadsheet
sampleset4000216_sampleannotations_GSE21802.csv
Sample Set Spreadsheet
Raw Signal
Raw Signal
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Samples Viewer / Editor

All fields are editable except the "Sample ID" column. To edit a cell, click within the cell. To edit a "date" cell, click on the calendar icon. To cancel an edit, press the ESC key.

Sample ID !Sample Title Tissue Patient Disease phase Mechanical ventilation Virus strain MV And Disease Phase
GSM542941
Healthy Control, biological rep1
Blood
control
control
 
none
Healthy Control
GSM542942
Healthy Control, biological rep2
Blood
control
control
 
none
Healthy Control
GSM542943
Healthy Control, biological rep3
Blood
control
control
 
none
Healthy Control
GSM542944
Healthy Control, biological rep4
Blood
control
control
 
none
Healthy Control
GSM542945
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep1
Blood
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542946
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep2
Blood
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542947
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep3
Blood
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542948
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep1
Blood
2
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542949
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep2
Blood
2
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542950
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep1
Blood
3
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542951
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep4
Blood
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542952
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep3
Blood
5
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542953
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep1
Blood
5
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542954
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep5
Blood
6
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542955
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep2
Blood
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542956
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep3
Blood
8
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542957
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep2
Blood
4
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542958
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep4
Blood
9
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542959
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep4
Blood
10
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542960
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep5
Blood
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542961
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep6
Blood
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542962
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep6
Blood
10
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542963
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep5
Blood
5
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542964
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep3
Blood
6
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542965
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep7
Blood
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542966
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep8
Blood
8
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542967
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep9
Blood
11
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542968
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep7
Blood
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542969
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep10
Blood
12
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542970
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep4
Blood
13
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542971
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep8
Blood
13
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542972
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep5
Blood
14
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542973
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep9
Blood
14
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period
GSM542974
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep6
Blood
15
early period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_early period
GSM542975
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep6
Blood
16
early period
no
Pandemic influenza (A/H1N1 new subtype)
no_early period
GSM542976
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep11
Blood
17
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542977
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep12
Blood
17
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542978
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep13
Blood
18
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542979
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep14
Blood
19
late period
yes
Pandemic influenza (A/H1N1 new subtype)
yes_late period
GSM542980
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period,biological rep10
Blood
16
late period
no
Pandemic influenza (A/H1N1 new subtype)
no_late period

Group Sets View in Gene Expression Browser

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