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| Status |
Public on Oct 29, 2010 |
| Title |
Whole blood gene expression in Vietnamese dengue patients |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Dengue is a pan-tropic public health problem. In children, dengue shock syndrome (DSS) is the most common life-threatening complication. Predicting patients who may develop DSS may improve triage and treatment. To this end, we conducted a nested case-control comparison of the early host-transcriptional features in 24 DSS patients and 56 sex-, age-, virus serotype-matched uncomplicated dengue patients. In the first instance we defined the “early dengue” profile. The transcriptional signature in acute versus convalescent samples (≤72hrs post illness-onset) was defined by an over-abundance of interferon-inducible transcripts (31% of the 551 over-abundant transcripts), and canonical gene ontology terms that included response to virus, immune response, innate immune response and inflammatory response. Pathway and network analysis identified STAT1, STAT2, STAT3, IRF7, IRF9, IRF1, CEBPB and SP1 as key transcriptional factors mediating the early response. Strikingly, the only differences in the transcriptional signatures of early DSS and uncomplicated dengue cases was the greater abundance of several neutrophil-associated transcripts in patients who progressed to DSS, a finding supported by higher plasma concentrations of several canonical proteins associated with neutrophil-degranulation (BPI, ELA2, DEF1A). Elevated levels of neutrophil-associated transcripts were independent of the neutrophil count and also the genotype of the infecting virus, as genome-length sequences of DENV-1 (n=15) and DENV-2 (n=3) viruses sampled from DSS patients were phylogenetically indistinguishable from those sampled from uncomplicated dengue patients (32 DENV-1 and 9 DENV-2). Collectively, these data suggest an hitherto unrecognised association between neutrophil activation, pathogenesis and the development of DSS and point to future strategies for guiding prognosis.
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| Overall design |
112 patients: 80 with uncomplicated dengue, 32 with dengue shock syndrome
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| Contributor(s) |
Hoang L, Lynn DJ, Henn M, Birren BW, Lennon NJ, Le PT, Duong KT, Nguyen TT, Mai LN, Farrar JJ, Hibberd ML, Simmons CP |
| Citation(s) |
20943967 |
| Submission date |
Oct 28, 2010 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Long Hoang |
| E-mail(s) |
hoangtruonglong@gmail.com
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| Organization name |
OUCRU
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| Street address |
190 Ben Ham Tu
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| City |
Ho Chi Minh |
| ZIP/Postal code |
848 |
| Country |
Viet Nam |
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| Platforms (1) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
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| Samples (209)
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| Relations |
| BioProject |
PRJNA134357 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE25001_RAW.tar |
3.4 Mb |
(http)(custom) |
TAR |
| GSE25001_non-normalized.txt.gz |
28.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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