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循环 sTREM-1 作为儿童多系统炎症综合征(MIS-C)的预测生物标志物。

Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C).

机构信息

Departamento de Pediatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Departamento de Pediatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Universidade Paulista, UNIP, Sao Paulo, SP, Brazil.

出版信息

Cytokine. 2023 Jan;161:156084. doi: 10.1016/j.cyto.2022.156084. Epub 2022 Nov 18.

Abstract

The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-α concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.

摘要

严重急性呼吸综合征冠状病毒 2 引起的炎症反应加剧,促进了可溶性介质的产生,这些介质可作为 COVID-19 的诊断和预后生物标志物。在潜在的生物标志物中,可溶性髓系细胞触发受体 1(sTREM-1)已被描述为炎症严重程度的预测因子。目的是评估儿科 COVID-19 患者在急性和恢复期的 sTREM-1 和细胞因子血清浓度。这是一项前瞻性研究,纳入了 53 名急性 COVID-19 患儿/青少年(急性-CoV 组);54 名从 COVID-19 中康复的患者(Post-CoV 组)和 54 名对照(对照组)。三组均存在先前存在的慢性疾病,定义如下:免疫性疾病、神经障碍、肾功能和肝功能衰竭。三组按年龄、性别和相似的先前存在的慢性疾病相匹配。各组之间或按先前存在的慢性疾病单独分析时,sTREM-1 水平无差异。然而,急性-CoV 组中的 7 名多系统炎症综合征患儿(MIS-C)的 sTREM-1 分析表明,MIS-C 患者的 sTREM-1 浓度高于非 MIS-C 急性患者。然后,对急性 MIS-C 患者进行的接收者操作特征曲线分析(ROC)显示,MIS-C 患者的 AUC 显著为 0.870,sTREM-1 截断值>5781pg/mL 时,对疾病严重程度的敏感性为 71.4%,特异性为 91.3%,sTREM-1 水平高于该截断值的患者发生 MIS-C 的风险增加 22.85 倍(OR=22.85[95%CI 1.64-317.5],p=0.02)。急性期的细胞因子分析显示,IL-6、IL-8 和 IL-10 浓度升高,无论患者是否发生 MIS-C,在恢复期时这些水平均下降,甚至与对照组相比也是如此。Spearman 相关性分析在急性-CoV 组中产生了 sTREM-1 与 IL-12 和 TNF-α 浓度之间的正指数。我们的发现表明,sTREM-1 在儿科患者中具有良好的预测准确性,可作为早期筛查工具,用于监测 MIS-C 病例,即使在存在慢性潜在疾病的患者中也是如此。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c4f/9671781/fcc0dec04640/gr1_lrg.jpg

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