Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06519, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06519, USA; Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA.
Immunity. 2021 May 11;54(5):1083-1095.e7. doi: 10.1016/j.immuni.2021.04.003. Epub 2021 Apr 13.
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction. MIS-C patients showed elevated expression of cytotoxicity genes in NK and CD8 T cells and expansion of specific IgG-expressing plasmablasts. Clinically severe MIS-C patients displayed skewed memory T cell TCR repertoires and autoimmunity characterized by endothelium-reactive IgG. The alarmin, cytotoxicity, TCR repertoire, and plasmablast signatures we defined have potential for application in the clinic to better diagnose and potentially predict disease severity early in the course of MIS-C.
儿童多系统炎症综合征（MIS-C）是一种发生在轻度或无症状 SARS-CoV-2 感染后数周的危及生命的感染后并发症，具有不可预测性。我们使用单细胞 RNA 测序、流式细胞术、抗原受体库分析和无偏血清蛋白质组学对 MIS-C、成人 COVID-19 和健康的儿科及成人个体进行了分析，这些分析共同确定了 MIS-C 患者的特征性标记物，该标记物与疾病严重程度相关。尽管 MIS-C 患者没有证据表明存在活动性感染，但他们的 S100A 家族警报素水平升高，抗原呈递特征降低，提示髓系功能障碍。MIS-C 患者的 NK 和 CD8 T 细胞中细胞毒性基因表达上调，并且特异性表达 IgG 的浆母细胞扩增。临床症状严重的 MIS-C 患者表现出记忆 T 细胞 TCR 库的偏倚和以血管内皮反应性 IgG 为特征的自身免疫。我们定义的警报素、细胞毒性、TCR 库和浆母细胞特征具有在临床上应用的潜力，可以更好地在 MIS-C 病程早期进行诊断，并有可能预测疾病的严重程度。
