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CCL3、CCL5、IL-15、IL-1Ra 和 VEGF 构成了一个可靠的算法,可以根据特定病因的定义来区分 17DD-YF 初免后不良事件的类别。

CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions.

机构信息

Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil.

Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil.

出版信息

Vaccine. 2021 Jul 13;39(31):4359-4372. doi: 10.1016/j.vaccine.2021.05.101. Epub 2021 Jun 16.

Abstract

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI ("A1" class) from cases with other illnesses ("C" class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI ("A1" and "C" classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in "A1" as compared to "C" class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate "A1" from "C". Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify "A1" followed by VEGF as branch nodes to discriminate Wild Type YFV infection ("C(WT-YFV)") from cases with other illnesses ("C*"). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

摘要

在本研究中,定量检测了疑似 YF 疫苗接种后不良反应事件(YEL-AEFI)的一系列血清生物标志物,以提出一种可靠的实验室算法,将确诊的 YEL-AEFI(“A1”类)与其他疾病(“C”类)病例区分开来。我们的研究结果表明,与无 YEL-AEFI 的原发性疫苗(PV[第 3-28 天])和参考范围(RR)对照相比,YEL-AEFI(“A1”和“C”类)中观察到 CXCL8、CCL2、CXCL10、IL-1β、IL-6 和 TNF-α水平升高。值得注意的是,与“C”类相比,“A1”类中 CCL3、CCL4、CCL2、CCL5、IL-1β、IL-15、IL-1Ra 和 G-CSF 水平升高。Venn 图分析允许对生物标志物进行预筛选,以进一步分析性能指标。数据表明,CCL3、CCL5、IL-15 和 IL-1Ra 具有较高的总体准确性(AUC=1.00),可将“ A1”与“C”区分开来。根据特定病因的定义,提出了决策树算法,以区分 YEL-AEFI 病例,其总体准确性(91%)可靠。CCL3、CCL5、IL-15 和 IL-1Ra 作为根属性,用于识别“ A1”,随后以 VEGF 作为分支节点,将野型 YFV 感染(“C(WT-YFV)”)与其他疾病(“C*”)病例区分开来。总之,这些结果证明了血清生物标志物测量作为建立准确的实验室工具的潜在参数,用于 YEL-AEFI 病例的补充鉴别诊断。

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