Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection
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DOI:
10.1038/s41591-020-1054-6
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发表时间:
2020-08-18
期刊:
影响因子:
82.9
通讯作者:
Shankar-Hari, Manu
Shankar-Hari, Manu
中科院分区:
医学1区
文献类型:
--
作者:
Carter, Michael J.;Fish, Matthew;Shankar-Hari, Manu

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最近的报告强调了一种与严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)(1)相关的儿童新的临床综合征--儿童多系统炎症综合征(MIS-C)--包括多器官功能障碍和全身炎症(2-13)。我们对25例MIS-C患儿在急性期(23例,入院后72小时内病情最严重)、消退期(14例,临床改善)和恢复期(10例,首次就诊)进行了外周血白细胞表型分析,并用7名年龄匹配的健康对照组的样本进行了比较。在MIS-C队列中,17名(68%)儿童SARS-CoV-2血清阳性,提示有SARS-CoV-2感染史(14,15例),这些儿童有更严重的疾病。在MIS-C急性期,我们观察到IL-1β(IL-1β)、IL-6、IL-8、IL-10、IL-17、干扰素-γ和差异性T、B细胞亚群淋巴细胞减少。急性期中性粒细胞和单核细胞表面CD64高表达,γ-增量细胞和CD4(+)CCR7(+)T细胞高表达HLA-DR,提示这些免疫细胞群处于激活状态。抗原提呈细胞有低的HLA-DR和CD86表达,这可能是抗原提呈受损的迹象。这些特征在恢复期和恢复期恢复正常。总体而言,MIS-C表现为一种免疫致病[1],与川崎病不同。与SARS-CoV-2感染相关的多系统炎症综合征儿童的特征提供了对该疾病免疫致病特征的洞察。
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(1)-multisystem inflammatory syndrome in children (MIS-C)-which comprises multiorgan dysfunction and systemic inflammation(2-13). We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections(14,15), and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1 beta (IL-1 beta), IL-6, IL-8, IL-10, IL-17, interferon-gamma and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on gamma delta and CD4(+)CCR7(+)T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness(1)and appears distinct from Kawasaki disease.Characterization of a cohort of children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection provides insights into the immunopathogenic features of the disease.