Centre for Adolescent Rheumatology Versus Arthritis at University College London (UCL), University College London Hospitals (UCLH), Great Ormond Street Hospital (GOSH), London, UK.
UCL Great Ormond Street Institute for Child Health (ICH), UCL, London, UK.
Med. 2021 Sep 10;2(9):1093-1109.e6. doi: 10.1016/j.medj.2021.08.001. Epub 2021 Aug 14.
Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group.
Sera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C).
Despite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure.
Consequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies.
This work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children's Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust
儿童和成人之间针对冠状病毒（包括严重急性呼吸综合征冠状病毒 2 型[SARS-CoV-2]）的体液免疫存在差异，但原因尚不清楚，潜在的免疫功能障碍或抑制的影响也尚不清楚。在此，我们试图研究常见于该年龄段的季节性人类冠状病毒（HCoV）-OC43，在患有常见炎症性风湿病（幼年特发性关节炎[JIA]、幼年皮肌炎[JDM]和幼年系统性红斑狼疮[JSLE]）的儿童和青少年中，抗体免疫能力。
在 COVID-19 大流行之前，我们从 JIA（n=118）、JDM（n=49）和 JSLE（n=30）患者以及健康对照（n=54）儿童和青少年中采集了血清。我们使用基于敏感流式细胞术的检测来确定与 HCoV-OC43 的刺突和核蛋白反应的抗体滴度，并与多系统炎症综合征患儿（MIS-C）的血清中的相应滴度进行比较。
尽管存在免疫功能障碍和免疫抑制治疗，JIA、JDM 和 JSLE 患者仍保持与健康同龄人相当或更强的体液反应，这主要由针对 HCoV-OC43 刺突的免疫球蛋白 G（IgG）抗体主导，并且存在与 SARS-CoV-2 刺突发生交叉反应的 IgG 抗体。相比之下，针对 HCoV-OC43 和 SARS-CoV-2 核蛋白的反应表现出延迟的年龄依赖性类别转换，并且在 JIA、JDM 和 JSLE 患者中并未升高，这表明接触增加。
因此，自身免疫性风湿病及其治疗与刺突与核蛋白抗体的有利比例有关。
这项工作得到了青少年关节炎与关节炎对抗中心卓越中心的支持，英国研究与创新署的资助参考号 MR/R013926/1，大奥蒙德街儿童慈善机构，JM 基金会，肌炎英国，狼疮英国，以及 GOSH 和 UCLH 的英国国民健康保险制度生物医学研究中心。这项工作得到了弗朗西斯·克里克研究所的支持，该研究所的核心资金来自英国癌症研究中心、英国医学研究理事会和惠康信托基金会。
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