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
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DOI：
10.1186/cc13150
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发表时间：
2013-01-01
期刊：
影响因子：
15.1
通讯作者：
Venet, Fabienne
中科院分区：
文献类型：
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作者：
Cazalis, Marie-Angelique;Friggeri, Arnaud;Venet, Fabienne
前言：败血症综合征仍然是重症监护病房(ICU)死亡的主要原因。脓毒症患者迅速发展免疫功能障碍，其强度和持续时间与有害后果有关。据报道，脓毒症后主要组织相容性复合体(MHC)II类相关基因的mRNA表达减少。我们研究了它们在感染性休克患者全血中的mRNA水平是否可以预测其死亡率。在休克后第3天，用qRT-PCR法检测5种MHC-II类相关基因(CD74、HLA-DRA、HLA-DMB、HLA-DMA、CIITA)的mRNA表达，用流式细胞术检测单核细胞人类白细胞抗原-DR(mhla-DR)的表达。在mRNA标记物中，CD74(人类白细胞抗原-DR抗原相关不变链)的预后价值最高。计算受试者工作特征曲线下面积(AUC=0.67，95%可信区间(CI)=0.55~0.79；P=0.01)及最佳截断值。根据这一阈值进行分层后，生存曲线显示CD74mRNA水平降低与感染性休克后死亡率增加相关(对数等级检验，P=0.0043，危险比=3.0，95%CI：1.4~6.5)。重要的是，在包括常见临床混杂因素(即严重程度评分，P=0.026，优势比=3.4，95%可信区间：1.2~9.8)的多因素Logistic回归分析后，这种相关性仍然显著。结论：感染性休克后CD74mRNA表达降低显著预测28d死亡率。在一项更大规模的多中心研究中得到验证后，该生物标志物可能成为脓毒症患者死亡的有力预测因子。
Introduction: Septic 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.Methods: A 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.Results: A 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).Conclusion: Decreased 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.