Induction of lupus-related autoantibodies by TNF inhibitors

TNF 抑制剂诱导狼疮相关自身抗体

• 批准号: 10405223
• 负责人: Anne Davidson
• 金额: $ 68.41万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-19 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405223
• 关键词: Acute Disease; Antibody Response; Autoantibodies; Child; Disease; Etiology; Goals; Immunity; Inflammatory; Interferons; Lupus; Multisystem Inflammatory Syndrome in Children; Myocardial dysfunction; Onset of illness; Outcome; Plasma; Production; SARS-CoV-2 infection; Serum; Structure of germinal center of lymph node; Syndrome; TNF gene; Testing; Viral Antibodies; Virus; cytokine; genetic analysis; heart damage; inhibitor/antagonist; metabolic profile; young adult

Abstract This proposal seeks to test two hypotheses regarding the Multisystem Inflammatory Syndrome (MIS-C) recently identified in children and young adults infected with SARS-CoV-2. We hypothesize that there is a spectrum of disease from severe acute disease to MIS-C. Severe Cov acute disease is associated with low interferon production, poor control of virus and a germinal center derived antibody response to the virus leading to long term immunity while MIS- C is associated with high interferon, efficient control of virus, but an extrafollicular derived antibody response with poor long term immunity. We will test this hypothesis through a genetic analysis, analysis of serum cytokines and analysis of anti-viral antibodies. We also hypothesize that plasma metabolic profile of subjects with MIS-C will predict short term cardiac dysfunction and long term cardiac damage.

抽象的 该提案旨在检验有关多系统炎症综合征的两个假设 (MIS-C) 最近在感染 SARS-CoV-2 的儿童和年轻人中发现。我们 假设存在从严重急性疾病到 MIS-C 的一系列疾病。严重 冠状病毒急性疾病与干扰素产生量低、病毒控制不佳以及病毒感染有关。 生发中心衍生的对病毒的抗体反应导致长期免疫，而 MIS- C与高干扰素、病毒的有效控制有关，但滤泡外来源的 抗体反应，长期免疫力差。我们将通过遗传来检验这个假设 分析、血清细胞因子分析和抗病毒抗体分析。我们还假设 MIS-C 受试者的血浆代谢特征可预测短期心功能障碍 和长期心脏损伤。