Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis.
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.
Pankla
Rungnapa
R
Department of Clinical Immunology, Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, 123 Mittraparp Road, Khon Kaen, 40002, Thailand. Vrungnapa@gmail.com
Buddhisa
Surachat
S
Berry
Matthew
M
Blankenship
Derek M
DM
Bancroft
Gregory J
GJ
Banchereau
Jacques
J
Lertmemongkolchai
Ganjana
G
Chaussabel
Damien
D
D000328:Adult; D000368:Aged; D015415:Biomarkers; D016957:Burkholderia pseudomallei / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000235:genetics* / Q000382:microbiology*; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D018805:Sepsis / Q000235:genetics* / Q000382:microbiology*; D014158:Transcription, Genetic
D015415:Biomarkers