Immune Profiling of Encephalitis

脑炎的免疫分析

• 批准号: 9169078
• 负责人: NANCY L MONSON
• 金额: $ 25.83万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169078
• 关键词: Antibodies; Antibody Repertoire; Antigens; Autoimmune Process; Autoimmune encephalitis; B-Lymphocytes; Benign; Binding; Biological Assay; Brain Diseases; Cells; Cerebrospinal Fluid; Clinical; Data; Databases; Detection; Development; Diagnosis; Disease; Effectiveness; Encephalitis; Excision; Frequencies; Genes; Glutamate Receptor; Goals; Immune; Immune system; Immunoglobulin-Secreting Cells; Infection; Inflammatory; Maps; Membrane; Memory B-Lymphocyte; Monitor; N-Methylaspartate; NMDA receptor A1; Neurons; Outcome; Ovarian Teratoma; Pathogenesis; Patients; Peripheral; Population Control; Proteins; Recovery; Recurrence; Risk; Staging; Surface; Symptoms; Target Populations; Testing; Time; antigen binding; crosslink; deep sequencing; multiple sclerosis patient; neuroimaging; neurophysiology; peripheral blood; receptor; response; tumor

PROJECT SUMMARY Encephalitis is an inflammatory disease of the brain caused by infection or autoimmune conditions. The most common type of autoimmune encephalitis (AE) is associated with high titers of antibodies against N-methyl-D- aspartate type glutamate receptors (NMDARs), termed αNMDAR-AE. Anti-NMDAR antibodies bind, cross-link, and internalize NMDAR receptors leading to altered neuronal function. Removal of anti-NMDAR antibodies has thus been the focus of first-line therapy, but recurrent attacks occur even in treated patients. Anti-NMDAR antibodies are produced by antibody secreting cells (ASCs), which arise from the memory B cell pool. We hypothesize that memory B cells and ASCs of αNMDAR-AE patients express antibodies that bind to NMDARs. Establishing that the memory B cell pool of αNMDAR-AE patients harbors a high frequency of NMDAR-reactive memory B cells would be the first step towards understanding the immunopathogenesis of αNMDAR-AE, and may prompt consideration of additive therapies that would effectively remove NMDAR- reactive memory B cells early in the treatment and management of αNMDAR-AE patients.

项目摘要 脑炎是一种由感染或自身免疫性疾病引起的大脑炎症性疾病。最 一种常见的自身免疫性脑炎（AE）与抗N-甲基-D- 天冬氨酸型谷氨酸受体（NMDARs），称为αNMDAR-AE。抗NMDAR抗体结合，交联， 并内化NMDAR受体，导致神经元功能改变。去除抗NMDAR抗体， 因此成为一线治疗的重点，但即使在接受治疗的患者中也会发生复发性发作。 抗NMDAR抗体由抗体分泌细胞（ASC）产生，其产生自记忆B细胞 池我们假设αNMDAR-AE患者的记忆B细胞和ASCs表达与 NMDAR。确定αNMDAR-AE患者的记忆B细胞库具有高频率的 NMDAR-反应性记忆B细胞将是理解免疫发病机制的第一步。 αNMDAR-AE，并可能促使考虑有效清除NMDAR的添加治疗- 反应性记忆B细胞在αNMDAR-AE患者的治疗和管理中的作用。