An integrative model with HLA-DR, CD64, and PD-1 for the diagnostic and prognostic evaluation of sepsis.
An integrative model with HLA-DR, CD64, and PD-1 for the diagnostic and prognostic evaluation of sepsis.
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DOI：
10.1002/iid3.1138
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发表时间：
2024-01
影响因子：
3.2
通讯作者：
Zhang, Anqiang
中科院分区：
文献类型：
--
作者：
Chen, Guosheng;Chong, Huimin;Zhang, Peng;Wen, Dalin;Du, Juan;Gao, Chu;Zeng, Shi;Zeng, Ling;Deng, Jin;Zhang, Kejun;Zhang, Anqiang
脓毒症是一种危及生命的器官功能障碍，由宿主对感染的反应失调和进行性免疫抑制引起，死亡率高。HLA - DR、CD64和PD - 1被认为是预测败血症的有用生物标志物。然而，这些生物标志物组合的能力尚未明确。进行了一项观察性病例对照研究，包括30名败血症患者，30名重症监护病房（ICU）的危重症患者和32名健康个体。在第1、3、5天检测患者外周血免疫细胞和亚群中HLA - DR、CD64和PD - 1的表达水平，并收集患者的临床信息。我们在组间比较了这些生物标志物，并评估了单一和联合生物标志物对脓毒症死亡率的预测有效性。结果显示，PD‐1在CD4−CD8−T上的表达（PD‐1+CD4−CD8−T）分别为19.19%±10.78%和9.88%±1.79%,p =。004)细胞和中性粒细胞CD64指数（nCD64指数）(9.15±5.46∶5.33±2.34,p =。与非脓毒症危重症患者相比，第1天脓毒症患者外周血单核细胞HLA - DR表达（mHLA - DR+）显著升高（13.26%±8.06% vs. 30.17%±21.42%,p = 2.54 × 10−4）。重要的是，PD‐1+CD4−CD8−T的表达(OR = 0.622, 95% CI = 0.423-0.916, p =。016)和mHLA博士+ (OR = 1.146, 95% CI -1.295 = 1.014, p =。029)与败血症死亡率显著相关。对于脓毒症的诊断，mHLA‐DR+、PD‐1+CD4−CD8−T和nCD64指标表现出中等的个体表现，3种生物标志物联合使用具有更大的诊断价值（AUC = 0.899, 95% CI = 0.792-0.962）。在联合模型中加入PCT后，AUC增加到0.936 （95% CI = 0.840-0.983）。对于脓毒症死亡率，PD‐1+CD4−CD8−T和mHLA‐DR+联合预测脓毒症患者预后的能力较好，AUC = 0.921 （95% CI = 0.762-0.987）。这些发现表明，HLA - DR、CD64和PD - 1联合检测在脓毒症的诊断和预测预后方面优于单个指标。目前的结果表明，免疫抑制的三种生物标志物可作为脓毒症患者的诊断或预后标志物。这是基于以下发现：(1)mHLA - DR+和PD - 1 + CD4 - CD8 - T细胞百分比和中性粒细胞CD64指数在脓毒症患者和非脓毒症患者之间存在显著差异；此外，ICU中合并死亡和未合并死亡的脓毒症患者的mHLA - DR+和PD - 1 + CD4 - CD8 - T细胞百分比也有显著差异；(2)当采用产生最高AUC的线性组合时，诊断或预后脓毒症标志物的鉴别能力显著增强。mHLA - DR+和PD - 1 + CD4 - CD8 - T共同为脓毒症患者ICU死亡率提供了良好的预测能力。mHLA - DR+和PD - 1 + CD4 - CD8 - T在该队列中的表现可与基于临床和生物标志物的败血症死亡率预测工具相媲美。
Sepsis is a life‐threatening organ dysfunction caused by a dysregulated host response to infection and progressive immunosuppression with high mortality. HLA‐DR, CD64, and PD‐1 were assumed to be useful biomarkers for sepsis prediction. However, the ability of a combination of these biomarkers has not been clarified. An observational case‐control study was conducted that included 30 sepsis patients, 30 critically ill patients without sepsis admitted to the intensive care unit (ICU), and 32 healthy individuals. The levels of HLA‐DR, CD64, and PD‐1 expression in peripheral blood immune cells and subsets was assayed on Days 1, 3, and 5, and the clinical information of patients was collected. We compared these biomarkers between groups and evaluated the predictive validity of single and combined biomarkers on sepsis mortality. The results indicate that PD‐1 expression on CD4−CD8−T (PD‐1+CD4−CD8−T) (19.19% ± 10.78% vs. 9.88% ± 1.79%, p = .004) cells and neutrophil CD64 index (nCD64 index) (9.15 ± 5.46 vs. 5.33 ± 2.34, p = .001) of sepsis patients were significantly increased, and HLA‐DR expression on monocytes (mHLA‐DR+) was significantly reduced (13.26% ± 8.06% vs. 30.17% ± 21.42%, p = 2.54 × 10−4) compared with nonsepsis critically ill patients on the first day. Importantly, the expression of PD‐1+CD4−CD8−T (OR = 0.622, 95% CI = 0.423–0.916, p = .016) and mHLA‐DR+ (OR = 1.146, 95% CI = 1.014–1.295, p = .029) were significantly associated with sepsis mortality. For sepsis diagnosis, the mHLA‐DR+, PD‐1+CD4−CD8−T, and nCD64 index showed the moderate individual performance, and combinations of the three biomarkers achieved greater diagnostic value (AUC = 0.899, 95% CI = 0.792–0.962). When adding PCT into the combined model, the AUC increased to 0.936 (95% CI = 0.840–0.983). For sepsis mortality, combinations of PD‐1+CD4−CD8−T and mHLA‐DR+, have a good ability to predict the prognosis of sepsis patients, with an AUC = 0.921 (95% CI = 0.762–0.987). These findings indicate that the combinations of HLA‐DR, CD64, and PD‐1 outperformed each of the single indicator in diagnosis and predicting prognosis of sepsis. The present results have shown that three biomarkers of immunosuppression may serve as diagnostic or prognostic markers for septic patients. This was based on the following findings: (1) the percentage of mHLA‐DR+ and PD‐1 + CD4−CD8− T cells and the neutrophil CD64 index were significantly different between patients with and without sepsis; furthermore, the percentage of mHLA‐DR+ and PD‐1 + CD4‐CD8‐ T cells was also significantly different between septic patients with and without death in the ICU; (2) there was a significant gain in discriminative power of diagnostic or prognostic sepsis markers when the linear combination that yielded the highest AUC was employed. mHLA‐DR+ and PD‐1 + CD4‐CD8‐T together provide good predictive ability for ICU mortality among subjects with sepsis. The performance of mHLA‐DR+ and PD‐1 + CD4‐CD8‐T in this cohort rivals established clinical‐ and biomarker‐based tools for mortality prediction in sepsis.
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DOI：
10.1186/cc10112
发表时间：
2011
期刊：
Critical care (London, England)
影响因子：
--
作者：
Guignant C;Lepape A;Huang X;Kherouf H;Denis L;Poitevin F;Malcus C;Chéron A;Allaouchiche B;Gueyffier F;Ayala A;Monneret G;Venet F
通讯作者：
Venet F
脓毒症引起的免疫抑制的免疫监测方法的进展
影响因子：
7.3
作者：
通讯作者：
--
影响因子：
38.9
作者：
通讯作者：
--
影响因子：
8.8
作者：
Vincent, JL;de Mendonca, A;Blecher, S
通讯作者：
Blecher, S
影响因子：
2.1
作者：
Dai, Ji;Jiang, Wenjie;Ge, Zhijun
通讯作者：
Ge, Zhijun