Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis

被引:151
作者
Pankla, Rungnapa [1 ,2 ,3 ]
Buddhisa, Surachat [1 ]
Berry, Matthew [4 ]
Blankenship, Derek M. [5 ]
Bancroft, Gregory J. [6 ]
Banchereau, Jacques [2 ,3 ]
Lertmemongkolchai, Ganjana [1 ]
Chaussabel, Damien [2 ,3 ]
机构
[1] Khon Kaen Univ, Fac Associated Med Sci, Ctr Res & Dev Med Diagnost Labs, Dept Clin Immunol, Khon Kaen 40002, Thailand
[2] Baylor Inst Immunol Res, Cooperat Ctr Translat Res Human Immunol & Biodef, Baylor Natl Inst Allergy & Infect Dis NIAID, Dallas, TX 75204 USA
[3] Baylor Res Inst, Dallas, TX 75204 USA
[4] Natl Inst Med Res, Ridgeway, Div Immunoregulat, London NW7 1AA, England
[5] Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA
[6] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
来源
GENOME BIOLOGY | 2009年 / 10卷 / 11期
基金
美国国家卫生研究院;
关键词
REAL-TIME PCR; GENE-EXPRESSION; BURKHOLDERIA-PSEUDOMALLEI; PERIPHERAL-BLOOD; CLINICAL-EVALUATION; MONONUCLEAR-CELLS; HLA-DR; SEPSIS; SHOCK; EPIDEMIOLOGY;
D O I
10.1186/gb-2009-10-11-r127
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates. Results: We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of patients with septicemic melioidosis (n = 32), patients with sepsis caused by other pathogens (n = 31), and uninfected controls (n = 29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T-cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway. Conclusions: Blood transcriptional patterns distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.
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页数:22
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