PDF(Pubmed)
Abstract：
Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.
摘要：
儿童多系统炎症综合征(MIS-C)是COVID-19的一种潜在危及生命的并发症。导致严重疾病的病理生理机制知之甚少。这项研究利用了一组特征明确的COVID-19或MIS-C住院儿童的临床样本来比较免疫介导的生物标志物。我们的目标是确定可以解释的免疫分子，在某种程度上,为什么某些感染SARS-CoV-2的儿童患上了MIS-C。我们假设2型辅助性T细胞介导的炎症可以引发自身抗体，这可能是中重度COVID-19（COVID+）和MIS-C队列之间观察到的一些差异的原因。我们对血液白细胞进行计数，并测量所选血清细胞因子的水平，趋化因子,COVID-19抗原抗体，以及出现在康涅狄格州学术医疗中心的儿童的自身抗体，美国。MIS-C组的中性粒细胞/淋巴细胞和嗜酸性粒细胞/淋巴细胞比率明显高于COVID+组。IgM和IgA,但在MIS-C队列中,SARS-CoV-2受体结合域的IgG抗体显著高于COVID+队列.与COVID和SARS-CoV-2阴性队列相比，MIS-C儿童的某些2型细胞因子（白介素（IL）-4，IL-5，IL-6，IL-8，IL-10，IL-13和IL-33）的血清水平显着升高。与SARS-CoV-19阴性对照相比，MIS-C患儿的脑抗原和正五聚蛋白的IgG自身抗体更高，与COVID+和SARS-CoV-19阴性对照相比，患有MIS-C的儿童的IgG抗-contactin相关蛋白样2（caspr2）水平更高。我们推测某些COVID-19患者的自身免疫反应可能会引起导致MIS-C的病理生理变化。自身免疫的触发因素和导致2型炎症的因素需要进一步研究。
