Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
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DOI：
10.1016/j.cell.2020.09.034
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发表时间：
2020-11-12
期刊：
影响因子：
64.5
通讯作者：
Bogunovic, Dusan
中科院分区：
文献类型：
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作者：
Gruber, Conor N.;Patel, Roosheel S.;Bogunovic, Dusan
最初，人们认为儿童不会感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的疾病。然而，疫情爆发一个月后，一种新的儿童多系统炎症综合征(MIS-C)出现了。在此，我们报告了9例MIS-C病例的免疫学特征。所有的MIS-C患者都有SARS-CoV-2接触过的证据，抗体反应具有完整的中和能力。细胞因子分析发现炎症(IL-18和IL-6)、淋巴细胞和髓系趋化和激活(CCL3、CCL4和CDCP1)以及粘膜免疫失调(IL-17A、CCL20和CCL28)的特征增加。外周血免疫表型分析显示非经典单核细胞减少，NK和T淋巴细胞亚群减少，提示渗出到受影响的组织。最后，对MIS-C血浆的自身抗原反应性的分析揭示了已知的疾病相关自身抗体(抗La)和识别内皮细胞、胃肠道和免疫细胞抗原的新候选抗体。所有患者均接受了抗IL-6R抗体和/或静脉注射免疫球蛋白治疗，病情迅速缓解。
Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.