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住院儿童多系统炎症综合征的细胞因子特征。

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome.

机构信息

Department of Clinical Immunology, Institute of Paediatrics, Faculty of Medicine, Jagiellonian University Medical College, Wielicka 265, Krakow, 30-663, Poland.

Institute of Veterinary Sciences, University Center of Veterinary Medicine JU-AU, University of Agriculture in Kraków, al. Mickiewicza 24/28, Krakow, 30-059, Poland.

出版信息

Sci Rep. 2024 Oct 1;14(1):22803. doi: 10.1038/s41598-024-73956-x.

Abstract

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients' sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7-10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7-10 days of hospitalization and therapy, including IL-1α, IL-1β, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

摘要

儿童多系统炎症综合征(MIS-C)的病因,常发生于 COVID-19 感染后,目前仍不清楚。本研究揭示了 COVID-19 感染后,MIS-C 患者血清中细胞因子分析的结果,包括静脉注射免疫球蛋白(IVIG)和糖皮质激素(GCS)治疗前后。在这项研究中,我们采用了一种全面的 45 细胞因子谱,包括广泛认可的促炎和抗炎细胞因子以及生长因子,以及其他可溶性介质。分析描绘了患者血清中三种主要的细胞因子浓度模式。模式 1 主要以促炎细胞因子(IL-6、IL-15、IL-1ra、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子α(TNFα)、C-X-C 基序趋化因子配体 10(CXCL10/IP-10)和 IL-10)为特征,入院时浓度升高,住院治疗后迅速恢复正常。模式 2 包括细胞因子(IL-17A、IL-33、IFNγ、血管内皮生长因子(VEGF)和程序性死亡配体 1(PD-L1)),入院时浓度中度升高,尽管进行了治疗,但在住院 7-10 天后仍持续存在。模式 3 包括细胞因子,入院 7-10 天后浓度升高,包括 IL-1α、IL-1β、IL-2、IL-13、血小板衍生生长因子 AA/BB(PDGF AA/BB)。MIS-C 患者的细胞因子谱观察到从急性炎症到维持炎症的转变,进而诱导体液记忆机制和各种防御机制,有助于恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e75/11445419/71f0e54ba6d7/41598_2024_73956_Fig1_HTML.jpg

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