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COVID-19 前川崎病静脉注射免疫球蛋白后的多模态免疫动力学。

Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin.

机构信息

Clinical Immunology and Vaccinology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Clinical Immunology and Vaccinology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy.

出版信息

Clin Immunol. 2024 Oct;267:110349. doi: 10.1016/j.clim.2024.110349. Epub 2024 Aug 24.

Abstract

Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature. APBB1IP demonstrated an association with coronary artery involvement (CAI) and was significantly higher in CAI+ compared to CAI- patients. Integrative analysis revealed a transient reduction in CD4+ EM T cells and a comprehensive immune activation and exhaustion. Following treatment, Tregs at both frequency and gene expression levels revealed immune dynamics of recovery. Overall, our data provide insights into KD, which may offer valuable information on prognostic indicators and possible targets for novel treatments.

摘要

尽管取得了进展,但川崎病(KD)的分子机制和静脉注射免疫球蛋白(IVIG)减轻炎症过程的能力仍未得到很好的理解。为了描述这种情况,对 KD 患者的纵向样本进行了血浆蛋白质组谱、流式细胞术和 T 细胞亚群的基因表达分析,并与两个对照组进行了比较。急性期样本的系统水平分析显示了 KD 的独特炎症特征,主要涉及 Th1 和 Th17 介质,并揭示了一个潜在的疾病严重程度特征。APBB1IP 与冠状动脉受累(CAI)相关,在 CAI+患者中明显高于 CAI-患者。综合分析显示 CD4+ EM T 细胞一过性减少,以及全面的免疫激活和衰竭。治疗后,Treg 的频率和基因表达水平均显示出恢复的免疫动态。总的来说,我们的数据为 KD 提供了深入的了解,这可能为预后指标和新的治疗方法提供有价值的信息。

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