An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease.
An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease.
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DOI：
10.1038/s41467-022-30357-w
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发表时间：
2022-05-16
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
儿童多系统炎症综合征（MIS-C）是一种在COVID-19大流行期间出现的疾病，但与川崎（KD）的大流行前综合征有许多共同的临床特征。在这里，我们使用在SARS-CoV-2感染的背景下开发的两种基因签名的计算工具箱来比较这两种综合征，即，病毒大流行（ViP）和严重-ViP特征和13-转录物特征先前被证明是KD的诊断，并验证了我们在全血RNA序列、血清细胞因子和福尔马林固定的心脏组织中的发现。结果表明，KD和MIS-C与COVID-19处于相同的宿主免疫应答连续体上。这两种儿科综合征都集中在以IL 15/IL 15 RA为中心的细胞因子风暴上，提示免疫发病机制的共享近端途径;然而，它们在其他实验室参数和心脏表型上存在分歧。ViP特征揭示了MIS-C中独特的靶向细胞因子途径，与KD相比，MIS-C在严重程度谱中的位置更沿着，并确定了可用于监测严重程度的关键临床（心功能降低）和实验室（血小板减少症和嗜酸性粒细胞减少症）参数。COVID-19感染后的儿童可能会发生多系统炎症综合征。在这里，作者分析了基因特征，表明MIS-C与川崎的大流行前炎症综合征具有相同的宿主免疫反应，但在疾病严重程度方面更沿着
Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity. Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity
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影响因子：
38.9
作者：
Abidi, Khalid;Belayachi, Jihane;Abouqal, Redouane
通讯作者：
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川崎病的治疗。
影响因子：
5.2
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影响因子：
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82.9
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Gnjatic S
影响因子：
3.1
作者：
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通讯作者：
BASS, DA