Perioperative Gene Expression Analysis for Prediction of Postoperative Sepsis

Hinrichs, Carl; Kotsch, Katja; Buchwald, S; Habicher, Marit; Saak, Nicole; Gerlach, Herwig; Volk, Hans‐Dieter; Keh, Didier

doi:10.1373/clinchem.2009.133876

Cited by 27 publications

(18 citation statements)

References 34 publications

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“…Moreover, in addition to other studies, these results highlight the potential of using transcriptomic biomarkers in the clinic [18]. The utility of such biomarkers lies in their capacity to provide timely information beyond that which is readily available from routine physiologic data and clinical examination.…”

Section: Discussionmentioning

confidence: 67%

Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

et al. 2013

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IntroductionSeptic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients.MethodsA total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry.ResultsA significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8).ConclusionDecreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients.

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Section: Discussionmentioning

confidence: 67%

Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

et al. 2013

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“…Moreover, CD3 expression on T lymphocytes was reduced in septic shock patients in comparison with healthy volunteers [34]. Similar decreased expression was observed at the mRNA level in patients developing sepsis or severe sepsis postoperatively [35] and in trauma patients [36]. Finally, CD28 expression (delivering a positive co-signal after ligation to B7.1 or B7.2) was depressed in trauma patients' anergic T cells and may contribute to incomplete activation of these cells [36].…”

Section: Discussionmentioning

confidence: 80%

Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients

et al. 2011

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IntroductionSeptic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients.MethodsThis prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed.ResultsWe observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration.ConclusionsThese findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.

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“…This is consistent with a study in which investigators observed lower perioperative IL1B expression in patients who subsequently developed postoperative sepsis. [30] Second, IL2RB (22q13.1) encodes the beta subunit of the interleukin-2 receptor. It is expressed by lymphocytes and by binding with interleukin-2 (IL-2) leads to T-cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Traumatic Injury, Early Gene Expression, and Gram-Negative Bacteremia*

Thompson

Park

Maier

et al. 2014

Critical Care Medicine

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Rationale Bacteremic trauma victims have a higher risk of death than their non-bacteremic counterparts. The role that altered immunity plays in the development of bacteremia is unknown. Objective Using an existing dataset, we sought to determine if differences in early post-injury immune-related gene expression are associated with subsequent gram-negative bacteremia (GNB). Design Retrospective cohort study, a secondary analysis of the Glue Grant database. Subjects Severely injured blunt trauma patients. Setting Seven level one trauma centers across the United States. Measurements Total leukocyte gene expression was compared between the subjects that developed GNB and those that did not. Main Results We observed that GNB was an independent risk factor for death (OR, 1.86; P=0.015). We then compared gene expression at 12 and 96 hours after injury in ten subjects who subsequently developed GNB matched to 26 that did not. At 12 hours, expression of 64 probes differed ≥1.5-fold; none represented genes related to innate or adaptive immunity. By 96 hrs, 102 probes were differentially expressed with 20 representing 15 innate or adaptive immunity genes; including downregulation of IL1B and upregulation of IL1R2, reflecting suppression of innate immunity in GNB subjects. We also observed downregulation of adaptive immune genes in the GNB subjects. Conclusions By 96 hours after injury, there are differences in leukocyte gene expression associated with the development of GNB, reflecting suppression of both innate and adaptive immunity. GNB after trauma is, in part, consequence of host immunity failure and may not be completely preventable by standard infection-control techniques.

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Perioperative Gene Expression Analysis for Prediction of Postoperative Sepsis

Cited by 27 publications

References 34 publications

Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients

Traumatic Injury, Early Gene Expression, and Gram-Negative Bacteremia*

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