Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease
Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease
复制标题
DOI：
10.1172/jci144554
复制
发表时间：
2021-03-15
影响因子：
15.9
通讯作者：
Alsina, Laia
中科院分区：
文献类型：
--
作者：
Esteve-Sole, Ana;Anton, Jordi;Alsina, Laia
与SARS-CoV-2大流行相关的多系统炎症综合征最近在儿童中被描述（MIS-C），部分与川崎（KD）重叠。我们假设（a）MIS-C和大流行前KD细胞因子谱可能是独特的，并证明观察到的临床差异，（B）SARS-CoV-2特异性免疫复合物（IC）可能解释MIS-C的免疫病理学。74名儿童包括在内：14名MIS-C，9名通过PCR检测为SARS-CoV-2阳性的非MIS-C（COVID）患者，14名大流行前KD患者和37名健康对照（HC）。在治疗前的血清或血浆样本中定量34种循环细胞因子，并在MIS-C患者中评估循环SARS-CoV-2 IC的存在。与HC相比，MIS-C和KD组显示大多数细胞因子显著升高，其中IFN-γ诱导的应答标志物（包括IFN-γ、IL-18和IP-10）和炎性单核细胞活化标志物（包括MCP-1、IL-1 α和IL-1 RA）是炎症的主要触发因素。在线性判别分析中，MIS-C和KD特征重叠;然而，MIS-C患者亚组（MIS-C+）在IFN-γ、IL-18、GM-CSF、RANTES、IP-10、IL-1 α和SDF-1以及巨噬细胞活化综合征的早期体征方面与其余MIS-C患者不同。在MIS-C患者中未检测到循环SARS-CoV-2 IC。我们的研究结果表明，IFN-γ在MIS-C的发病机制中起着重要作用，这可能与治疗管理有关。
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-gamma-induced response markers (including IFN-gamma, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1 alpha, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-C-plus) differentiated from the remaining MIS-C patients in IFN-gamma, IL-18, GM-CSF, RANTES, IP-10, IL-1 alpha, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-gamma in the pathogenesis of MIS-C, which may be relevant for therapeutic management.