Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock |
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Authors: | Marie-Angélique Cazalis Arnaud Friggeri Laura Cavé Julie Demaret Véronique Barbalat Elisabeth Cerrato Alain Lepape Alexandre Pachot Guillaume Monneret Fabienne Venet |
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Institution: | 1.Joint Research Unit “Sepsis” Hospices Civils de LYON – bioMérieux, Hôpital Edouard Herriot, Lyon, France;2.Hospices Civils de LYON, Intensive Care Units, Centre Hospitalier Lyon-Sud, Pierre Bénite, France;3.Hospices Civils de LYON, Immunology Laboratory, Hôpital Edouard Herriot, 5 place d’Arsonval, Lyon 69437, France |
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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. |
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