Identifying key regulatory genes in the whole blood of septic patients to monitor underlying immune dysfunctions
There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3677 genes, biological pathway analysis identified 86 genes significantly down-regulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis including lymphocyte depletion, reduced T lymphocyte activation and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of down-regulation found in non-survivors compared to survivors. The results show that whole blood gene-expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression based assay, to assess immunosuppression and guide immunotherapy in future clinical trials.
|ISBN||1540-0514 (Electronic) 1073-2322 (Linking)|
|Authors||Parnell, G. P. ; Tang, B. M. ; Nalos, M. ; Armstrong, N. J. ; Huang, S. J. ; Booth, D. R. ; McLean, A. S.;|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/23807251|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11995|