Biologic Effects of Anti-Ganglioside Antibodies
抗神经节苷脂抗体的生物学效应
基本信息
- 批准号:8874311
- 负责人:
- 金额:$ 33.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-15 至 2019-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAffinityAnimal ModelAnti-Inflammatory AgentsAnti-inflammatoryAntibodiesAntigen-Antibody ComplexAutoantibodiesAutoimmune ProcessAutoimmune ResponsesAxonBindingCD209 geneCell surfaceCell-Mediated CytolysisCellsComplexDataDependencyDevelopmentDiseaseFab ImmunoglobulinsFailureFc ImmunoglobulinsFc ReceptorFractionationFucoseGangliosidesGoalsGuillain-Barré SyndromeHealthHumanIgG ReceptorsImmuneImmune systemImmunoglobulin GImmunologic ReceptorsIn VitroIndividualInflammationInjuryIntravenous ImmunoglobulinsLectinLeftMass Spectrum AnalysisMediatingMediator of activation proteinMicrogliaMinorModelingMultiple SclerosisNatural regenerationNerveNerve CrushNeurogliaNeurologicNeuronsNeuropathyParalysedPathogenicityPathway interactionsPatientsPeripheral NervesPeripheral Nervous SystemPoliomyelitisPolysaccharidesPopulationPre-Clinical ModelRecombinantsRecoveryRecruitment ActivityResearchRoleSchwann CellsSeverity of illnessSialic AcidsSiteSpecificityStructureSurface Plasmon ResonanceSyndromeTestingTherapeuticTissuesTransgenic MiceTransplantationantibody-dependent cell cytotoxicityaxon regenerationbasecomparative efficacyglycosylationin vivoinhibiting antibodyinjuredmacrophagenerve injuryparent grantpreventreinnervationrepairedrole modelsialylation
项目摘要
DESCRIPTION (provided by applicant): After the near eradication of polio, Guillain-Barre syndrome (GBS) is the commonest cause of acute flaccid paralysis. Anti-ganglioside/glycan antibodies (Abs) are the most frequently recognized autoimmune responses in immune neuropathies grouped under the term GBS. Despite the availability of two immunomodulatory therapies, a significant proportion of patients are left with permanent neurologic sequelae. Patients with neurologic sequelae almost always have failure of axon regeneration and target reinnervation. Several studies indicate that specific anti-glycan Abs associate with poor recovery. Our group examined the effects of anti- glycan Abs on peripheral nerve repair and found these Abs inhibit regeneration of injured axons in preclinical models. The overall goals of this translational project are to study mechanisms underlying pathobiologic effects of anti-ganglioside Abs on axon regeneration and to develop strategies that could prevent the deleterious effects of anti-glycan Abs on nerve repair. Our preliminary results show that specific activating Fc-gamma receptors (Fc?Rs) particularly on macrophages recruited in the injured nerves are key determinants of Ab-mediated inhibition of nerve repair. Further, glycosylation of anti-ganglioside Abs is critical in their interactions with Fc?Rs and deglycosylation of anti-glyca Abs suppresses their inhibitory effects on nerve repair. Further, sialylated- fraction of human intravenous immunoglobulins (sIVIG), a minor component of IVIG, suppresses Ab-mediated inhibition of axon regeneration. We hypothesize that anti-glycan Abs bind to gangliosides on neural cell surfaces to form immune complexes on the proximal tips of injured axons and these in turn bind to specific activating Fc?Rs expressed by adjacent glial cells to induce tissue inflammation affecting axon regeneration. Furthermore, IgG Fc interactions with innate immune receptors are critically dependent on the IgG glycosylation and this glycosylation status can be manipulated (on pathogenic Abs and IVIG) to alter anti- ganglioside Ab- or IVIG-mediated effects. This renewal application will test these hypotheses by the following specific aims: Aim 1 will examine the role of specific Fc?Rs and glial cells expressing Fc?Rs in mediating nerve injury; Aim 2 will examine the role of N-glycan structures, carried by anti-glycan Abs, in their interactions with Fc?Rs to induce inflammation; and Aim 3 will examine the role of Fc/IgG sialylation as determinants of IVIG efficacy via the so-called 'DC-SIGN-Th2' anti-inflammatory pathway. These translational and 'proof of principle' studies have pathobiologic and therapeutic implications for failure of axon regeneration particularly that seen after immune insults/inflammation in autoimmune conditions like immune neuropathies and multiple sclerosis where failure of axonal repair is central to severity of the disease and recovery.
描述(由申请人提供):在几乎根除脊髓灰质炎后,格林-巴利综合征(GBS)是急性弛缓性麻痹的最常见原因。抗神经节苷脂/聚糖抗体(Abs)是在术语GBS下分组的免疫神经病中最常见的自身免疫反应。尽管有两种免疫调节疗法可用,但仍有相当比例的患者留下永久性神经系统后遗症。有神经系统后遗症的患者几乎总是轴突再生和靶神经再支配失败。几项研究表明,特异性抗聚糖抗体与恢复不良相关。我们的小组检查了抗聚糖抗体对周围神经修复的作用,发现这些抗体在临床前模型中抑制损伤轴突的再生。这个翻译项目的总体目标是研究抗神经节苷脂抗体对轴突再生的病理生物学作用的机制,并制定策略,可以防止抗聚糖抗体对神经修复的有害影响。我们的初步结果表明,特异性激活Fc-γ受体(Fc?Rs),特别是在受损神经中募集的巨噬细胞上的表达是Ab介导的神经修复抑制的关键决定因素。此外,糖基化的抗神经节苷脂抗体是至关重要的,在他们的相互作用与Fc?Rs和抗glyca Ab的去糖基化抑制其对神经修复的抑制作用。此外,人静脉内免疫球蛋白的唾液酸化部分(sIVIG)(IVIG的次要组分)抑制Ab介导的轴突再生抑制。我们假设,抗聚糖抗体结合神经细胞表面的神经节苷脂,形成免疫复合物的近端损伤轴突和这些反过来结合到特定的激活Fc?邻近胶质细胞表达受体诱导组织炎症影响轴突再生。此外,IgG Fc与先天免疫受体的相互作用严重依赖于IgG糖基化,并且可以操纵这种糖基化状态(对致病性Ab和IVIG)以改变抗神经节苷脂Ab或IVIG介导的作用。这一更新申请将测试这些假设的以下具体目标:目标1将检查特定的Fc的作用?Rs和神经胶质细胞表达Fc?RS介导神经损伤;目的2将研究N-聚糖结构的作用,进行抗聚糖抗体,在他们的相互作用与Fc?Rs诱导炎症;目的3将检查Fc/IgG唾液酸化作为IVIG功效的决定因素通过所谓的“DC-SIGN-Th 2”抗炎途径的作用。这些转化和“原理证明”研究对轴突再生失败具有病理生物学和治疗意义,特别是在自身免疫性疾病如免疫神经病和多发性硬化中的免疫损伤/炎症后观察到的轴突再生失败,其中轴突修复失败对疾病的严重程度和恢复至关重要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KAZIM A SHEIKH其他文献
KAZIM A SHEIKH的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('KAZIM A SHEIKH', 18)}}的其他基金
Blockade of colony stimulating factor 1 receptor to reduce inflammatory nerve injury
阻断集落刺激因子 1 受体以减少炎症神经损伤
- 批准号:
10195632 - 财政年份:2021
- 资助金额:
$ 33.25万 - 项目类别:
Modulation of FcRn: A strategy to prevent autoantibody-mediated nerve injury
FcRn 的调节:预防自身抗体介导的神经损伤的策略
- 批准号:
8684787 - 财政年份:2014
- 资助金额:
$ 33.25万 - 项目类别:
Modulation of FcRn: A strategy to prevent autoantibody-mediated nerve injury
FcRn 的调节:预防自身抗体介导的神经损伤的策略
- 批准号:
8806622 - 财政年份:2014
- 资助金额:
$ 33.25万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8446439 - 财政年份:2011
- 资助金额:
$ 33.25万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8245788 - 财政年份:2011
- 资助金额:
$ 33.25万 - 项目类别:
Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
无创成像在临床上量化周围神经损伤和修复
- 批准号:
8106764 - 财政年份:2011
- 资助金额:
$ 33.25万 - 项目类别:
Biologic Effects of Anti-Ganglioside Antibodies
抗神经节苷脂抗体的生物学效应
- 批准号:
8761854 - 财政年份:2007
- 资助金额:
$ 33.25万 - 项目类别:
Biologic effects of anti-ganglisiode antibodies
抗神经节苷脂抗体的生物学效应
- 批准号:
7695001 - 财政年份:2007
- 资助金额:
$ 33.25万 - 项目类别:
Biologic effects of anti-ganglisiode antibodies
抗神经节苷脂抗体的生物学效应
- 批准号:
7844987 - 财政年份:2007
- 资助金额:
$ 33.25万 - 项目类别:
Biologic effects of anti-ganglisiode antibodies
抗神经节苷脂抗体的生物学效应
- 批准号:
7320622 - 财政年份:2007
- 资助金额:
$ 33.25万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 33.25万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 33.25万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 33.25万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 33.25万 - 项目类别:
Studentship