PATHOGENIC MECHANISMS IN MYASTHENIA GRAVIS
重症肌无力的致病机制
基本信息
- 批准号:3399865
- 负责人:
- 金额:$ 11.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1984
- 资助国家:美国
- 起止时间:1984-07-01 至 1990-06-30
- 项目状态:已结题
- 来源:
- 关键词:acetylcholine acute disease /disorder antibody antigen antibody reaction autoimmune disorder chronic disease /disorder disease /disorder model electromyography electron microscopy electrophysiology guinea pigs humoral immunity laboratory mouse laboratory rat model design /development monoclonal antibody myasthenia gravis nicotinic receptors pathologic process tissue /cell culture
项目摘要
The overall goal of this study is to characterize the sequence of
events through which anti-acetylcholine receptor (anti-AChR)
antibodies induce the abnormalities in the antibody-mediated
autoimmune disease, myasthenia gravis (MG). It involves an
analysis of the three forms of experimental autoimmune
myasthenia gravis (EAMG), described in our laboratory, that are
induced by injection of monoclonal antibody (mAb) to AChR. The
acute form follows a single injection of mAb and is associated
with cellular inflammation and necrosis of the muscle endplate
membrane. The chronic phase, which occurs after repeated
injections, is characterized by simplified endplate membranes
with decreased AChR content in the absence of inflammation, as
is typical for MG. However, these animals failed to demonstrate
significant weakness or electrophysiologic evidence of blocked
neuromuscular transmission. The hyperacute form, which is
induced only by anti-AChR mAbs that block AChR function, may
be viewed as the mirror image of the chronic form i.e. marked
blockade of neuromuscular transmission with morphologically
normal endplates. The specific aims of this proposal consist of an
analysis of the mechanisms involved in the production of both the
hyperacute and the chronic forms of EAMG in rats. A more
complete model of MG will then be produced using various types
of mAbs acting via different mechanisms, and perhaps at
different times in the course of the illness. Finally the
hypotheses derived from these animal studies will be tested by
analyzing the characteristics of the antibodies from patients with
MG in relation to the disease characteristics. The study will
make use of a wide range of immunologic, biochemical,
electrophysiologic and morphologic techniques. The knowledge
gained from the study of this "model" autoimmune disease should
provide clues to the development of specific immunotherapy of
MG as well as providing information that is likely to be applicable
to other less well understood autoimmune diseases.
本研究的总体目标是表征
抗乙酰胆碱受体(抗AChR)事件
抗体诱导抗体介导的
自身免疫性疾病,重症肌无力(MG)。 它涉及到一个
实验性自身免疫三种形式的分析
重症肌无力(EAMG),在我们的实验室中描述,
通过注射抗AChR的单克隆抗体(mAb)诱导。 的
单次注射mAb后出现急性形式,
伴有细胞炎症和肌肉终板坏死
膜的 慢性期,发生在反复
注射,其特征在于简化终板膜
在没有炎症的情况下,AChR含量降低,
这是典型的MG。 然而,这些动物未能证明
明显的虚弱或电生理证据表明
神经肌肉传递 超急性型,
仅由阻断AChR功能的抗AChR单克隆抗体诱导,
被视为慢性形式的镜像,即标记
阻断神经肌肉传递,
正常终板。 该提案的具体目标包括:
分析了生产过程中所涉及的机制,
超急性和慢性形式的EAMG大鼠。 一个更
MG的完整模型,然后将使用各种类型的
单克隆抗体通过不同的机制发挥作用,
在疾病的不同时期。 最后
这些动物研究的假设将通过以下方法进行检验:
分析结核病患者的抗体特征,
MG与疾病特征有关。 这项研究将
利用广泛的免疫学,生物化学,
电生理学和形态学技术。 知识
从这种“模型”自身免疫性疾病的研究中获得的结果应该
为开发特异性免疫疗法提供线索。
MG以及提供可能适用的信息
其他不太了解的自身免疫性疾病。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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DAVID P RICHMAN其他文献
DAVID P RICHMAN的其他文献
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{{ truncateString('DAVID P RICHMAN', 18)}}的其他基金
Development of Animal Models of Anti-MuSK Myasthenia
抗MuSK肌无力动物模型的建立
- 批准号:
8048710 - 财政年份:2010
- 资助金额:
$ 11.25万 - 项目类别:
Development of Animal Models of Anti-MuSK Myasthenia
抗MuSK肌无力动物模型的建立
- 批准号:
8152160 - 财政年份:2010
- 资助金额:
$ 11.25万 - 项目类别:
IX INTERNATIONAL CONFERENCE ON MYASTHENIA GRAVIS
第九届重症肌无力国际会议
- 批准号:
2038867 - 财政年份:1997
- 资助金额:
$ 11.25万 - 项目类别:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
ACCHR 表位的结构/功能分析
- 批准号:
3100129 - 财政年份:1987
- 资助金额:
$ 11.25万 - 项目类别:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
ACCHR 表位的结构/功能分析
- 批准号:
3100128 - 财政年份:1987
- 资助金额:
$ 11.25万 - 项目类别:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
ACCHR 表位的结构/功能分析
- 批准号:
3100131 - 财政年份:1987
- 资助金额:
$ 11.25万 - 项目类别:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
ACCHR 表位的结构/功能分析
- 批准号:
3100126 - 财政年份:1987
- 资助金额:
$ 11.25万 - 项目类别:
STRUCTURE/FUNCTION ANALYSIS OF ACCHR EPITOPES
ACCHR 表位的结构/功能分析
- 批准号:
3100130 - 财政年份:1987
- 资助金额:
$ 11.25万 - 项目类别: