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通过PD-L1抗体亲和微流控(PAAM)芯片联合CD64和CD123生物标志物用于微量临床样本中脓毒症的早期诊断和严重程度评估

Combining CD64 and CD123 Biomarkers for Sepsis Early Diagnosis and Severity Assessment via PD-L1 Antibody Affinity Microfluidic (PAAM) Chip in Trace Clinical Samples.

作者信息

Yan Haoni, Zhang Yan, Shi Yujie, Ding Jiahui, Su Hengxing, Su Wenqiong, Wang Yan, Mao Yanfei, Khattab Tawfik A, Al-Qahtani Salhah D, Abdulla Aynur, Jiang Lai, Ding Xianting

机构信息

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200092, China.

Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.

出版信息

Anal Chem. 2025 Apr 15;97(14):7928-7937. doi: 10.1021/acs.analchem.4c07123. Epub 2025 Apr 3.

DOI:10.1021/acs.analchem.4c07123
PMID:40177943
Abstract

Sepsis, a lethal organ dysfunction caused by a dysregulated host response to infection, is the leading cause of worldwide in-hospital mortality. However, the early diagnostic methods for sepsis are still urgent for guiding accurate antibiotic usage and improving the survival rate of the patients. Herein, we constructed a PD-L1 antibody affinity microfluidic (PAAM) chip for early sepsis diagnosis and severity assessment. The chip was used to capture PD-L1-expressing leukocytes from whole blood samples obtained from healthy control (HC) volunteers ( = 15) and sepsis patients on day 1 (D1) and day 7 (D7) ( = 20), and there was a statistically significant difference between HC and sepsis patients ( < 0.0001), and the AUC was 0.96. However, there was no significant difference in the number of cells captured on-chip between sepsis patients on D1 and D7 ( = 0.16). Therefore, we performed immunofluorescence staining of PD-L1, CD64, and CD123 on the chip. The results showed that the combination of PD-L1, CD64, and CD123 for sepsis diagnosis had an AUC of 0.98, and there was a significant difference in PD-L1/CD64/CD123 leukocytes between sepsis patients on D1 and on D7 ( < 0.0001). In conclusion, we found that the combination of multiple biomarkers was more precise and dependable for sepsis diagnosis and severity assessment.

摘要

脓毒症是由宿主对感染的失调反应引起的致命性器官功能障碍,是全球住院患者死亡的主要原因。然而,脓毒症的早期诊断方法对于指导准确使用抗生素和提高患者生存率仍迫在眉睫。在此,我们构建了一种用于脓毒症早期诊断和严重程度评估的PD-L1抗体亲和微流控(PAAM)芯片。该芯片用于从健康对照(HC)志愿者(n = 15)以及脓毒症患者第1天(D1)和第7天(D7)(n = 20)采集的全血样本中捕获表达PD-L1的白细胞,HC与脓毒症患者之间存在统计学显著差异(P < 0.0001),曲线下面积(AUC)为0.96。然而,D1和D7的脓毒症患者在芯片上捕获的细胞数量没有显著差异(P = 0.16)。因此,我们对芯片上的PD-L1、CD64和CD123进行了免疫荧光染色。结果表明,PD-L1、CD64和CD123联合用于脓毒症诊断的AUC为0.98,D1和D7的脓毒症患者之间的PD-L1/CD64/CD123白细胞存在显著差异(P < 0.0001)。总之,我们发现多种生物标志物的组合对于脓毒症诊断和严重程度评估更精确、可靠。

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