Giant MagnetoResistive (GMR) Sensors for Measuring Influenza Vaccine

7.项目摘要/摘要 这个新目标4的首要目标是检验SARS-CoV-2(CoV-2)导致自身免疫的假设 感染患者亚群中的疾病(AI)。我们对282例COVID19例患者的336份新冠肺炎样本(3个地理位置不同的4个新冠肺炎队列)的初步研究鉴定了自身抗体和 人工智能的临床证据。为了验证自身抗体在感染CoV-2后产生的假设，我们将使用 用于识别自身抗体所针对的蛋白质的自身抗原阵列，其中一些自身抗体可能导致致病 炎症反应可能导致肺、皮肤和其他组织损伤，凝血功能失调， 内皮功能障碍和血管病变。然后我们将测试自身抗体是通过 不同的机制，包括分子模仿和产生受体阻断的抗细胞因子抗体 (ACA)应对“细胞因子风暴”。我们假设，感染CoV-2会导致两种不同的结果： (I)预期结果--中和CoV-2的保护性反应；或(Ii)导致 症状性自身免疫或自身炎症性疾病。Aim 4.1将检验CoV-2引起的假设 利用我们的习俗“新冠肺炎”开发自身抗体和可分类的自身免疫性疾病 自身抗原阵列“包含来自影响肺、内皮和皮肤的疾病的常见自身抗原。 AIM 4.2将表征针对CoV-2和其他冠状病毒蛋白的血清抗体，以及 与AIM 1中的自身抗体相关，通过使用我们的“新冠肺炎病毒阵列”能够同时 对许多不同野生型和变异型病毒蛋白和多肽的抗体进行定量。病毒反应 将与临床结果相关，包括自身抗体的发展和临床进展 自身免疫力。Aim 4.3将测试CoV-2通过以下机制引起自身免疫的假设 交叉反应(分子模拟)和细胞因子风暴，产生受体阻断的ACA。我们将使用 探索这些机制的各种基于实验室的技术，包括从 血清、免疫共沉淀和交叉结合分析。总之，拟议中的实验将开始 量化CoV-2对AI的影响，确定哪些抗原和特定AI与CoV-2相关，以及 为我们从机理上理解新冠肺炎的发病机制做出贡献，为大规模研究奠定基础 流行病学研究确定CoV-2感染导致的自身免疫程度，以及对卫生保健系统和经济的长期影响。

7. Project Summary/Abstract The overarching goal of this New Aim 4 is to test the hypothesis that SARS-CoV-2 (CoV-2) causes autoimmune disease (AI) in a subset of infected patients. Our preliminary studies on 336 COVID-19 samples from 282 COVID19 patients (four COVID-19 cohorts in three geographically distinct regions) have identified autoantibodies and clinical evidence of AI. To test the hypothesis that autoantibodies develop following CoV-2 infection, we will use autoantigen arrays to identify proteins targeted by autoantibodies, some of which may cause pathogenic inflammatory responses that could mediate lung, skin, and other tissue injury, dysregulated coagulation, endothelial dysfunction, and vasculopathy. We will then test the hypothesis that autoantibodies develop through different mechanisms including molecular mimicry and generation of receptor-blocking anti-cytokine antibodies (ACA) in response to “cytokine storm”. We hypothesize that infection with CoV-2 induces 2 different outcomes: (i) the desired outcome - protective responses that neutralize CoV-2; or (ii) pathogenic responses that lead to symptomatic autoimmunity or autoinflammatory disease. Aim 4.1 will test the hypothesis that CoV-2 causes development of autoantibodies and classifiable autoimmune diseases by leveraging our custom “COVID-19 Autoantigen Array” comprising common autoantigens from diseases that affect the lung, endothelium and skin. Aim 4.2 will characterize serum antibodies specific for proteins from CoV-2 and other coronaviruses, and correlate with autoantibodies in Aim 1, by using our “COVID-19 Viral Array” capable of simultaneously quantitating antibodies against many different wild-type and mutant viral proteins and peptides. Viral responses will be correlated with clinical outcomes including development of autoantibodies, and progression to clinical autoimmunity. Aim 4.3 will test the hypothesis that CoV-2 causes autoimmunity through mechanisms including cross-reactivity (molecular mimicry) and cytokine storm which generates receptor-blocking ACA. We will use a variety of lab-based techniques to explore these mechanisms, including purification of antigen-specific IgG from serum, co-immunoprecipitation, and cross-binding assays. Together, the proposed experiments will begin to quantify the impact of CoV-2 on AI, identify which antigens and specific AI are associated with CoV-2, and contribute to our mechanistic understanding of COVID-19 pathogenesis, setting the stage for large-scale epidemiology studies to determine the extent of autoimmunity that results from CoV-2 infection, as well as longterm impacts on the health care system and economy.