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

Abstract

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.

The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn

“…sCD74 also may act as a biomarker for burn-related sepsis. In contrast to our findings, Cazalis et al reported decreased mRNA levels of CD74 in septic shock patients and an association with increased risk of mortality [23]. This apparent contradiction may be explained by the dynamics of soluble factors which depend on the underlying insult.…”

Expression of HLA‐DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia

“…Cazalis et al . studied mRNA expression of five different MHC class II related genes, including CD74 ( HLA‐DRA associated invariant chain) and HLA‐DRA , and found CD74 to be the strongest predictor of negative outcomes. However, that study was based on only one sample per patient, collected 3–4 days after onset of septic shock.…”

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

“…Low monocyte HLA-DR expression levels serve as a surrogate marker of monocyte "anergy," development of nosocomial infections, and death (48)(49)(50). Several studies correlate low monocyte HLA-DR expression levels with diminished monocyte function and reduced antigen-specific lymphocyte proliferation (51,52), suggesting that monocyte anergy and immune suppression independently contribute to the increased risk of adverse events in sepsis.…”