Regulation of Pathogenic Plasma Cells in Human SLE

人类系统性红斑狼疮致病性浆细胞的调控

• 批准号: 10187509
• 负责人: Ignacio E. Sanz
• 金额: $ 174.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-19 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187509
• 关键词: Acute; Address; Adult; Airway Disease; Antibodies; Antibody Response; Antigens; B-Lymphocytes; Biological Assay; Blood; Blood specimen; Borrelia burgdorferi; COVID-19; COVID-19 pandemic; Cells; Clostridium difficile; Collaborations; Color; Coronavirus; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Excision; Freezing; Goals; Gold; Health; Health Personnel; Human; Immune; Immune response; Immunity; Immunoassay; Immunoglobulin-Secreting Cells; Immunology procedure; Infection; Influenza; Investigation; Laboratories; Lead; Legal patent; Licensing; Lower Respiratory Tract Infection; Lyme Disease; Lyme Infection; Nose; Nucleocapsid Proteins; Pathogenicity; Patients; Peptides; Plasma Cells; Pneumonia; Proteins; Quarantine; Recording of previous events; Regulation; Resolution; Respiratory Failure; Respiratory syncytial virus; Risk; Sampling; Serum; Severe Acute Respiratory Syndrome; Staphylococcus aureus; Streptococcus pneumoniae; Swab; Systemic Lupus Erythematosus; Technology; Testing; Time; Universities; Vaccines; Validation; Viral; Viral Load result; Virus; Virus Diseases; acute infection; base; commercialization; follow-up; influenzavirus; microbial; neutralizing monoclonal antibodies; novel; novel diagnostics; outcome forecast; pandemic disease; respiratory; response

Novel Immune Diagnostics of COVID-19 for Acute Infection, Prognosis of Severe Disease, and Resolution of Infection. The spreading COVID-19 pandemic has once again highlighted the need to develop better diagnostic tests and vaccines geared towards the enhancement of effective B cell responses and passive therapies through the administration of neutralizing monoclonal antibodies. Our application, will directly address the development of novel immune assays to diagnose acute COVID-19 infection, provide prognosis of patients who may develop severe respiratory complications, and identify immunity and disease resolution in asymptomatic adults during the course of this pandemic. Our laboratories with expertise in B cells and plasma cell responses to vaccines and influenza virus infections provide the basis for a novel diagnostic platform that interrogates circulating antibody secreting cells (ASC) when a patient is ill. This technology can diagnose the following microbial infections: Influenza virus, Respiratory syncytial virus (RSV) 1,2, Streptococcus pneumoniae, Staphylococcus aureus 3 , Clostridioides difficile (C. difficile) (Haddad et al, in review), and Borrelia burgdorferi (Lyme disease). Originally performed with fresh blood ASC in cumbersome Elispot immunoassays, Drs. Daiss and Lee at MicroB-plex, Inc. have streamlined the assay into a patented technology that utilizes a cultured supernatant of newly secreted antibodies from isolated blood ASC. The novel matrix is MENSA, a “media enriched with newly synthesized antibodies” and can be easily multiplexed with over 10-12 antigens (as shown in preliminary data). The cell free-MENSA matrix can be easily collected and frozen to evaluate the contemporaneous ASC responses at the time of illness. In addition, a negative MENSA after diagnosis can demonstrate viral clearance and resolution of the active immune response. In this supplement, we propose to develop a novel immune-based COVID-19 MENSA assay (1) to diagnose acute infection and (2) and to prognosticate patients at risk of respiratory failure. In addition, with resolution of infection, a negative COVID-19 MENSA and positive serum test will show immunity with disease resolution. All tests will be available for commercialization without a need for licensing specific for this COVID19 pandemic.

COVID-19的新型免疫诊断，用于急性感染，严重疾病的预后和 感染的分辨率。 传播的共同19-19大流行再次强调了需要进行更好的诊断测试和 旨在通过增强有效B细胞反应和被动疗法的疫苗 中和单克隆抗体的给药。我们的应用将直接解决 新型免疫可诊断急性共vid-19感染的免疫刺激，提供可能发展的患者的预后 严重的呼吸并发症，并确定无症状成年人的免疫学和疾病分辨率 这个大流行的过程。 我们的实验室在B细胞中具有专业知识和对疫苗的浆细胞反应并影响病毒感染 为新的诊断平台提供基础，该平台询问循环抗体分泌细胞（ASC） 病人病了。该技术可以诊断以下微生物感染：流感病毒，呼吸道 合成病毒（RSV）1、2，肺炎链球菌，金黄色葡萄球菌3 ，梭状芽胞杆菌艰难梭菌（艰难梭菌） （Haddad等人，综述）和Borrelia Burgdorferi（莱姆病）。最初以新鲜的血液ASC进行 繁琐的ELISPOT免疫测定，Drs。 Microb-Plex，Inc。的Daiss和Lee将测定方法简化为 利用孤立血液ASC的新分泌抗体的培养的上清液的专利技术。 新颖的矩阵是mensa，它是一种“富含新合成抗体的培养基”，可以很容易多样化 超过10-12抗原（如初步数据所示）。可以很容易地收集细胞不含细胞的mensa矩阵，并且 冻结以评估疾病时的当代ASC反应。另外，负男性 诊断后可以证明活跃免疫反应的病毒清除率和分辨率。在这个 补充，我们建议开发一种新型的基于免疫的Covid-19 Mensa分析（1）以诊断急性 感染和（2），并具有呼吸衰竭风险的经过验证的患者。另外，解决 感染，阴性covid-19 mensa和阳性血清测试将显示出与疾病的免疫学 解决。所有测试均可用于商业化，而无需针对此Covid19大流行的许可。