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immunopathogenesis of NMO-IgG and AQP4-specific T cells in neuromyelitis optica

NMO-IgG 和 AQP4 特异性 T 细胞在视神经脊髓炎中的免疫发病机制

基本信息

批准号：
9262280
负责人：
Michael Levy
金额：
$ 19.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9262280
关键词：
Adoptive Transfer African American Animal Model Antibodies Applications Grants Astrocytes Basic Science Binding Binding Sites Biological Markers Blindness Blocking Antibodies Blood - brain barrier anatomy Brain Cell Communication Cells Chronic Clinic Clinical Clinical Research Complement-Dependent Cytotoxicity Disease Doctor of Philosophy Environment Epitopes Ethnic Origin Experimental Autoimmune Encephalomyelitis Genetic Engineering Grant Helper-Inducer T-Lymphocyte Hospitals IgG1 Immune Immune Targeting Immunoglobulin Class Switching Immunoglobulin G Immunologic Factors Incidence Infiltration Inflammation Inflammatory Inflammatory Response Injectable Inpatients Institutes K-Series Research Career Programs Knockout Mice Mediating Mentors Mentorship Mission Multiple Sclerosis Mus National Institute of Neurological Disorders and Stroke Nervous system structure Neuraxis Neurology Neuromyelitis Optica Optic Nerve Optics Paralysed Pathogenesis Pathogenicity Pathologic Pathology Patients Peptides Phenotype Population Prevalence Recruitment Activity Research Research Activity Research Personnel Rest Rodent Model Role Scientist Series Serological Services Societies Spinal Spinal Cord Stroke T-Cell Immunologic Specificity T-Lymphocyte Testing Therapeutic Intervention Time Tissues Translating Transverse Myelitis United States Universities Wild Type Mouse Work age group aquaporin 4 body system design disease phenotype experimental study extracellular foot granulocyte immunoreaction insight nervous system disorder neuroimmunologic disease neuroimmunology neuroinflammation prevent professor public health relevance relapse risk targeted treatment water channel young woman

项目摘要

DESCRIPTION (provided by applicant): This is a proposal for a 5-year K08 Mentored Clinical Scientist Research Career Development Award from the National Institutes of Neurological Disease and Stroke (NINDS) to investigate the role of NMO-IgG and Aquaporin-4 specific T cells in the immunopathogenesis of neuromyelitis optical. Neuromyelitis optical (NMO) is a devastating neuroinflammatory disorder targeting the optic nerves and spinal cord leading to blindness and paralysis. NMO is associated with a serologic biomarker, the NMO-IgG, which targets the aquaporin-4 (AQP4) water channel on the end feet of astrocytes in the central nervous system. This grant is designed to elucidate the immunopathogenesis of neuromyelitis optical focusing on three aspects: 1. Characterizing the role of the NMO-IgG in inducing or exacerbating the NMO disease phenotype by recruiting granulocytes, 2. Identifying the target of the NMO-IgG on AQP4 in the spinal cord and optic nerves using specific anti-AQP4 antibodies, 3. Evaluating the role of Th17 cells specific for AQP4 in instigating and facilitating inflammation in the central nervous system. Each aim is complimentary to the whole project and will provide unique insights into the pathogenesis of NMO. The principle investigator for this project is Michael Levy, MD, PhD, and an Assistant Professor in the Department of Neurology at the Johns Hopkins University who is working under the mentorship of Peter Calabresi, MD, Professor and Director of the Division of Neuroimmunology at Johns Hopkins University. Dr. Calabresi is a leader in the clinical and research fields of multiple sclerosis and neuroimmunologic diseases. Together in one of the nation's most productive research environments, Dr. Levy will have 75% protected time to spend in the lab and use the rest of the time to translate his basic science work to the bedside in the NMO clinic and on the inpatient neurology service at Johns Hopkins Hospital.

描述(由申请人提供)：这是一项为期5年的K08临床科学家导师研究职业发展奖的提案，该奖项由美国国立神经疾病和中风研究所(NINDS)颁发，旨在调查NMO-IgG和Aquaporin-4特异性T细胞在视神经脊髓炎免疫发病机制中的作用。视神经脊髓炎(NMO)是一种以视神经和脊髓为靶点的破坏性神经炎性疾病，可导致失明和瘫痪。NMO与一种血清学生物标志物NMO-Ig G有关，NMO-Ig G靶向中枢神经系统星形胶质细胞末端足部的水通道AQP4。本研究旨在从三个方面阐明神经脊髓炎的免疫发病机制：1.研究NMO-Ig G通过募集粒细胞诱导或加重NMO病表型的作用；2.用特异性抗AQP4抗体确定脊髓和视神经AQP4上NMO-Ig G的靶点；3.评价AQP4特异性Th17细胞在炎症中的作用在中枢神经系统中。每个目标都是对整个项目的补充，并将为NMO的发病机制提供独特的见解。该项目的首席研究员是Michael Levy，医学博士，约翰霍普金斯大学神经学系助理教授，在约翰霍普金斯大学神经免疫学系主任、教授兼医学博士Peter Calabresi的指导下工作。卡拉布雷西博士是多发性硬化症和神经免疫学疾病临床和研究领域的领导者。在美国生产率最高的研究环境之一中，利维博士将有75%的受保护时间花在实验室里，剩下的时间用来将他的基础科学工作转移到NMO诊所的床边和约翰·霍普金斯医院的住院神经科服务上。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prevalence and characteristics of transverse myelitis and neuromyelitis optica spectrum disorders in the United Arab Emirates: A multicenter, retrospective study.

DOI：
10.1111/cen3.12458
发表时间：
2018-08
期刊：
Clinical & experimental neuroimmunology
影响因子：
0
作者：
Holroyd KB;Aziz F;Szolics M;Alsaadi T;Levy M;Schiess N
通讯作者：
Schiess N

Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica.

DOI：
10.1186/s40478-015-0207-1
发表时间：
2015-05-21
期刊：
Acta neuropathologica communications
影响因子：
7.1
作者：
Jones MV;Huang H;Calabresi PA;Levy M
通讯作者：
Levy M

Bevacizumab is safe in acute relapses of neuromyelitis optica.

DOI：
10.1111/cen3.12239
发表时间：
2015-11-01
期刊：
Clinical & experimental neuroimmunology
影响因子：
0
作者：
Mealy MA;Shin K;John G;Levy M
通讯作者：
Levy M

Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis.

DOI：
10.1016/j.jns.2015.05.013
发表时间：
2015-08-15
期刊：
JOURNAL OF THE NEUROLOGICAL SCIENCES
影响因子：
4.4
作者：
Mealy, Maureen A.;Whetstone, Anna;Orman, Gunes;Izbudak, Izlem;Calabresi, Peter A.;Levy, Michael
通讯作者：
Levy, Michael

Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange.