B cell phenotype and serum levels of interferons, BAFF, and APRIL in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C).

IF 2.4 Q1 PEDIATRICS
Adam Klocperk, Marketa Bloomfield, Zuzana Parackova, Ludovic Aillot, Jiri Fremuth, Lumir Sasek, Jan David, Filip Fencl, Aneta Skotnicova, Katerina Rejlova, Martin Magner, Ondrej Hrusak, Anna Sediva
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Abstract

Background: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19.

Results: We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients.

Conclusions: Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

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新冠肺炎相关儿童多系统炎症综合征(MIS-C)中的B细胞表型和干扰素、BAFF和APRIL的血清水平。
背景:与新冠肺炎相关的儿童多系统炎症综合征(MIS-C)是儿科新冠肺炎的晚期并发症,无论其严重程度如何,都是在最初感染SARS-CoV-2数周后发生的。其特征是高炎症、中性粒细胞增多、淋巴细胞减少和IFN-γ升高的T细胞活化。观察自身抗体的产生以及与系统性自身免疫性疾病(如系统性红斑狼疮(SLE))的相似性,我们在COVID-19后的MIS-C患者和健康儿童队列中探讨了B细胞表型和I型、II型和III型干扰素的血清水平,以及细胞因子BAFF和APRIL。结果:我们记录了IFN-γ的显著升高,α和IFN-。在MIS-C患者血清中BAFF升高,并伴随着所有B细胞亚型上BAFFR表达的降低。与健康的新冠肺炎后儿童相比,患者的浆母细胞比例明显较低。我们注意到,在4/35名测试的MIS-C患者中,IVIG前存在ENA Ro60自身抗体。结论:我们的工作显示了体液免疫在MIS-C中的参与,并暗示了与SLE的病理生理学相似,BAFF升高会驱动自身反应性B细胞产生自身抗体。
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CiteScore
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