Seven-Gene Transcriptomic Score Quantifies Immune Dysregulation in Sepsis on a Point-of-Care Platform
A prospective multicentre study identified a panel of three upregulated innate immune transcripts and four downregulated adaptive immune transcripts that together quantify systemic inflammation in sepsis. Validated in 246 patients on a point-of-care-compatible platform, the gene expression score discriminated definite infection from no infection with an AUC-ROC of 0.812, offering a novel tool for identifying at-risk patients and guiding immune interventions.
The original study
A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis - A Prospective Multicenter Phase II Diagnostic Study.
- Authors
- Bauer M, Giamarellos-Bourboulis EJ, Kortgen A, Möller E, Felsmann K, Cavaillon JM, et al.
- Journal
- EBioMedicine
- Type
- Journal Article, Multicenter Study
- PMID
- 27211554
Original abstract
Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up- (Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC=0.812 (95%-CI 0.755-0.869), p<0.0001). Down-regulated lymphocyte markers were associated with prognosis with good sensitivity but limited specificity. Quantifying systemic inflammation by assessment of both pro- and anti-inflammatory innate and adaptive immune responses provides a novel option to identify patients-at-risk and may facilitate immune interventions in sepsis.