Autoreactive processes in children in the initial period of multisystem inflammatory syndrome associated with SARS-CoV-2 and after rehabilitation

O. Obukhova, T. Ryabichenko, G. Skosyreva, A.O. Izyumov, Elena P. Timofeeva, Alya P. Shvayuk, Nadezhda N. Stankevich, M. L. Voevoda
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Abstract

BACKGROUND: The problem of the pathogenesis of the multisystem inflammatory syndrome (MIS-C), associated with SARS-CoV-2, remains relevant, but is still far from being resolved. In this regard. AIM: The aim our research was to study and evaluate the levels of autoantibodies to native and denatured DNA in the blood serum of children who underwent MIS-C, associated with SARS-CoV-2, in comparison with the initial period of the pathological process. MATERIALS AND METHODS: 101 children aged 2 to 17 years old were examined, 77 of them was with a confirmed diagnosis of MIS-C associated with SARS-CoV-2. We have formed 3 groups: group 1 — children with MIS-C upon admission to the hospital; group 2 — children who underwent MIS-C after a course of rehabilitation; group 3 — comparison group. All children underwent determination of the concentrations of IgG-autoantibodies to native and denatured DNA in blood serum, which was performed by EIA ELISA using commercial test systems of Vector-Best LLC (Russia) according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using the Statistica v. 10.0 application package. Statistical processing used the Newman–Keuls multiple comparison test. RESULTS: It was noted that both in the initial period of MIS-C and after rehabilitation, an increased content of autoantibodies to nDNA and dDNA was determined compared to the control group. At the same time, there was a significant excess of the levels of indicators in the post-rehabilitation period compared with the initial period of MIS-C. During a clinical examination of children who underwent MIS-C, most of them noted the appearance of pain in the joints. The results obtained indicate the persistence of inflammatory reactions with the development of an autoreactive component. This requires both the search for risk markers for the development of MIS-C and further monitoring of children who have undergone MIS-C to prevent autoimmune complications, including arthritis, damage to the vascular endothelium with the possible formation of thrombotic complications. CONCLUSIONS: In the acute period of MIS-C and after rehabilitation, increased levels of the average content of autoantibodies to nDNA and dDNA were noted compared to the control. Individual values of autoantibodies to nDNA and dDNA exceeded normative levels of the indicator were found in a significantly larger number of children in the post-rehabilitation period after MIS-C, and this excess was more pronounced compared to the acute period of the process. When assessing the clinical condition of children after MIS-C, most of them showed pain in the joints during exercise, abdominal and neurological disorders, and decreased tolerance to physical activity, which indicates persistent inflammatory reactions.
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与 SARS-CoV-2 相关的多系统炎症综合征初期和康复后儿童的自身反应过程
背景:与 SARS-CoV-2 相关的多系统炎症综合征(MIS-C)的发病机制问题仍然具有现实意义,但远未得到解决。在这方面目的:我们的研究旨在研究和评估与 SARS-CoV-2 相关的多系统炎症综合征(MIS-C)患儿血清中的原生 DNA 和变性 DNA 自身抗体水平,并与病理过程初期进行比较。材料和方法:我们对 101 名 2 至 17 岁的儿童进行了检查,其中 77 名儿童确诊为与 SARS-CoV-2 相关的 MIS-C。我们分成三组:第一组--入院时患有 MIS-C 的儿童;第二组--经过康复治疗后接受 MIS-C 的儿童;第三组--对比组。所有患儿都接受了血清中原生 DNA 和变性 DNA IgG 自身抗体浓度的检测,检测方法是使用 Vector-Best LLC(俄罗斯)公司的商用检测系统,按照制造商的说明进行 EIA ELISA 检测。所得结果的统计处理使用 Statistica v. 10.0 软件包进行。统计处理采用纽曼-克厄斯多重比较试验。结果:结果表明,与对照组相比,在 MIS-C 初期和康复后,nDNA 和 dDNA 的自身抗体含量都有所增加。同时,与 MIS-C 初期相比,康复后的指标水平明显偏高。在对接受 MIS-C 的儿童进行临床检查时,大多数人都发现关节出现疼痛。研究结果表明,炎症反应持续存在,并伴有自反应成分的发展。这就需要寻找发生 MIS-C 的风险标志物,并对接受 MIS-C 的儿童进行进一步监测,以防止出现自身免疫并发症,包括关节炎、血管内皮损伤以及可能形成的血栓并发症。结论:与对照组相比,在 MIS-C 急性期和康复后,nDNA 和 dDNA 自身抗体的平均含量均有所增加。在 MIS-C 术后康复期,发现 nDNA 和 dDNA 自身抗体的单个值超过指标正常水平的儿童人数明显增多,而且与急性期相比,这种超标现象更加明显。在评估 MIS-C 术后患儿的临床状况时,大多数患儿表现出运动时关节疼痛、腹部和神经失调以及对体育活动的耐受性下降,这表明炎症反应持续存在。
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