Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.
Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.
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DOI：
10.1172/jci171729
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发表时间：
2023-11-01
影响因子：
15.9
通讯作者：
Agbor-Enoh, Sean
中科院分区：
文献类型：
--
作者：
Andargie, Temesgen E.;Roznik, Katerina;Redekar, Neelam;Hill, Tom;Zhou, Weiqiang;Apalara, Zainab;Kong, Hyesik;Gordon, Oren;Meda, Rohan;Park, Woojin;Johnston, Trevor S.;Wang, Yi;Brady, Sheila;Ji, Hongkai;Yanovski, Jack A.;Jang, Moon K.;Lee, Clarence M.;Karaba, Andrew H.;Cox, Andrea L.;Agbor-Enoh, Sean
儿童多系统炎症综合征（MIS-C）是一种罕见但危及生命的高炎性疾病，由感染严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起，可导致儿童COVID-19 （pCOVID-19）。系统性组织损伤与MIS-C病理生理的关系尚不明确。我们利用血浆无细胞DNA （cfDNA）和血浆细胞因子测量的高灵敏度表观基因组学分析来识别组织损伤的频谱并收集机制见解。与儿童健康对照组（pHCs）和pCOVID-19患者相比，misc患者的cfDNA水平更高，cfDNA主要来自先天性免疫细胞、巨核红细胞前体细胞和非造血组织，如肝细胞、心肌细胞和肾细胞。非造血组织cfDNA水平表现出显著的个体差异，与misc的异质性临床表现一致。相比之下，适应性免疫细胞来源的cfDNA水平在MIS-C和pCOVID-19患者中是相当的。事实上，misc患者先天免疫细胞的cfDNA与先天免疫炎症细胞因子和非造血组织来源的cfDNA水平相关，这表明主要是先天免疫介导的反应导致了多系统病理。这些数据提供了对MIS-C发病机制的深入了解，并支持cfDNA作为一种敏感的生物标志物的价值，用于绘制MIS-C和其他可能的多器官炎症状况的组织损伤。
Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the pathophysiology of MIS-C is poorly defined. We leveraged the high sensitivity of epigenomics analyses of plasma cell-free DNA (cfDNA) and plasma cytokine measurements to identify the spectrum of tissue injury and glean mechanistic insights. Compared with pediatric healthy controls (pHCs) and patients with pCOVID-19, patients with MIS-C had higher levels of cfDNA primarily derived from innate immune cells, megakaryocyte-erythroid precursor cells, and nonhematopoietic tissues such as hepatocytes, cardiac myocytes, and kidney cells. Nonhematopoietic tissue cfDNA levels demonstrated significant interindividual variability, consistent with the heterogenous clinical presentation of MIS-C. In contrast, adaptive immune cell–derived cfDNA levels were comparable in MIS-C and pCOVID-19 patients. Indeed, the cfDNA of innate immune cells in patients with MIS-C correlated with the levels of innate immune inflammatory cytokines and nonhematopoietic tissue–derived cfDNA, suggesting a primarily innate immunity–mediated response to account for the multisystem pathology. These data provide insight into the pathogenesis of MIS-C and support the value of cfDNA as a sensitive biomarker to map tissue injury in MIS-C and likely other multiorgan inflammatory conditions.
DOI：
10.4274/jcrpe.galenos.2022.2022-4-7
发表时间：
2022-12-01
影响因子：
1.9
作者：
Elvan-Tüz A;Ayrancı İ;Ekemen-Keleş Y;Karakoyun İ;Çatlı G;Kara-Aksay A;Karadağ-Öncel E;Dündar BN;Yılmaz D
通讯作者：
Yılmaz D