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.

新的免疫诊断COVID-19急性感染，严重疾病的预后， 感染的解决。 不断蔓延的COVID-19大流行再次凸显了开发更好的诊断测试和 疫苗旨在通过增强有效的B细胞反应和被动疗法 施用中和单克隆抗体。我们的应用程序，将直接解决的发展 新的免疫检测方法诊断急性COVID-19感染，为可能发展为 严重呼吸系统并发症，并确定免疫力和疾病的解决过程中无症状的成人 这场大流行的进程。 我们的实验室在疫苗和流感病毒感染的B细胞和浆细胞反应方面具有专业知识 提供了一种新的诊断平台的基础，该平台在以下情况下询问循环抗体分泌细胞（ASC）： 病人生病了。该技术可以诊断以下微生物感染：流感病毒、呼吸道感染、 合胞病毒（RSV）1、2、肺炎链球菌、金黄色葡萄球菌3 、艰难梭菌（Clostridioides difficile，C. difficile） （Haddad等，综述中）和伯氏疏螺旋体（莱姆病）。最初使用新鲜血液ASC进行， MicroB-plex公司的Daiss和Lee博士说，已将分析简化为 该专利技术利用分离的血液ASC中新分泌抗体的培养上清液。 新的基质是MENSA，一种“富含新合成抗体的培养基”，可以很容易地进行多重检测。 具有超过10-12种抗原（如初步数据所示）。可以容易地收集无细胞-MENSA基质， 冷冻以评估患病时的同期ASC反应。此外，负MENSA 在诊断后可以证明病毒清除和主动免疫应答的消退。在这 作为补充，我们建议开发一种新的基于免疫的COVID-19 MENSA检测（1），以诊断急性 感染和（2）和预防有呼吸衰竭风险的患者。此外，随着决议 感染，阴性COVID-19 MENSA和阳性血清检测将显示对疾病的免疫力 分辨率所有测试将可用于商业化，而无需专门针对此次COVID 19大流行的许可。