Immune reactivity to synapsin in the neuropathy and ataxia of celiac disease

乳糜泻神经病变和共济失调中突触蛋白的免疫反应

基本信息

批准号：
7364150
负责人：
ARMIN ALAEDINI
金额：
$ 18.38万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
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：
2007-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7364150
关键词：
Address Affect Affinity Animals Antibodies Antibody Affinity Antibody Formation Antigen Targeting Ataxia Autoantigens Autoimmune Diseases Autoimmune Process Axonal Neuropathy Binding Binding Proteins Biosensor Celiac Disease Cerebellar Ataxia Characteristics Classification Clinical Complex Coupled Diagnosis Diet Disease Enzyme-Linked Immunosorbent Assay Epitope Mapping Epitopes Gliadin Gluten Human Idiopathic Neuropathy Immune Immunoblotting Immunoglobulin G Individual Inflammation Light Maps Mediating Molecular Mimicry Nervous system structure Neurologic Neurologic Deficit Neurons Neuropathy Oryctolagus cuniculus Pathology Patients Peripheral Nervous System Peripheral Nervous System Diseases Phenotype Proteins Serum Site Small Intestines Spectrum Analysis Surface Plasmon Resonance Symptoms Synapsin I Synapsins Synaptic Vesicles Syndrome Techniques Testing Tissues Treatment Efficacy Two-Dimensional Gel Electrophoresis Western Blotting Wheat anti-IgA base disease phenotype gastrointestinal symptom immunoaffinity chromatography nano nervous system disorder neurotransmitter release relating to nervous system research study

项目摘要

DESCRIPTION (provided by applicant): Neuropathy and ataxia are among the most common and debilitating extraintestinal complications occurring in patients with celiac disease or gluten sensitivity. These neurologic deficits are believed to be immune mediated, possibly driven by molecular mimicry. However, until now, no putative neural target antigen had been identified. In preliminary studies, we found that antibodies to wheat gliadin immunostain neurons in the nervous system. Using immunoblotting, immunoaffinity chromatography, 2- dimensional gel electrophoresis, and nano-LC/MS/MS techniques, we identified the cross-reactive autoantigen as synapsin I, a central and peripheral nervous system protein involved in neurotransmitter release. Epitope mapping revealed the major immunoreactive sites to be located in the functionally important C domain of synapsin I, which is known to mediate the interaction of the protein with synaptic vesicles. In addition, affinity purified human IgG and IgA anti-gliadin antibodies were also found to cross- react with synapsin I. Our hypothesis is that in some patients with celiac disease, the anti-gliadin antibody response cross-reacts with synapsin I and that the immune reactivity is associated with neurologic deficits in celiac disease, such as cerebellar ataxia or peripheral neuropathy. The following specific aims are proposed to address our hypothesis: i) To determine whether there is an association between antibody reactivity to synapsin I and celiac neuropathy or ataxia. 2) To determine whether specific antibody isotype or affinity is associated with the presence of neurological disease or particular phenotypes. 3) To map the epitope(s) of synapsin I targeted by human antibodies, determining whether reactivity against certain epitopes is associated with the occurrence of neurologic disease or a particular syndrome. The proposed studies are expected to shed light on how central and peripheral nervous system deficits may be associated with gluten sensitivity. They may also serve to provide a useful marker for the diagnosis of the associated peripheral neuropathy or cerebellar ataxia, and offer a rationale for examining the efficacy of therapies that target autoimmune mechanisms in affected individuals.

描述（由申请人提供）：神经病和共济失调是腹腔疾病或麸质敏感性患者中最常见和令人衰弱的肠外并发症之一。这些神经系统缺陷被认为是免疫介导的，可能是由分子模仿驱动的。但是，到目前为止，尚未发现假定的神经靶抗原。在初步研究中，我们发现神经系统中针对小麦麦芽麦苷免疫抑制蛋白神经元的抗体。使用免疫印迹，免疫亲和力色谱，2-维凝胶电泳和纳米-LC/MS/MS技术，我们确定了交叉反应自身抗原是突触I，是突触I，是一种中枢和周围神经系统蛋白参与神经素释放剂的中枢和周围神经系统蛋白。表位映射揭示了主要的免疫反应位点位于突触素I功能上重要的C结构域中，已知可以介导蛋白质与突触囊泡的相互作用。 In addition, affinity purified human IgG and IgA anti-gliadin antibodies were also found to cross- react with synapsin I. Our hypothesis is that in some patients with celiac disease, the anti-gliadin antibody response cross-reacts with synapsin I and that the immune reactivity is associated with neurologic deficits in celiac disease, such as cerebellar ataxia or peripheral neuropathy.提出了以下具体目的来解决我们的假设：i）确定抗体反应性与突触I与乳糜泻神经病或共济失调之间是否存在关联。 2）确定特定的抗体同种型或亲和力是否与神经系统疾病或特定表型的存在有关。 3）绘制由人抗体靶向的突触I的表位，确定针对某些表位的反应性是否与神经系统疾病或特定综合征的发生有关。拟议的研究预计将阐明中心神经系统缺陷如何与面筋敏感性相关。它们还可以为诊断相关的周围神经病或小脑共济失调提供有用的标记，并为检查受影响个体的自身免疫机制的疗法的疗效提供了理由。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel immune response to gluten in individuals with schizophrenia.

DOI：
10.1016/j.schres.2009.08.009
发表时间：
2010-05
期刊：
SCHIZOPHRENIA RESEARCH
影响因子：
4.5
作者：
Samaroo, Diana;Dickerson, Faith;Kasarda, Donald D.;Green, Peter H. R.;Briani, Chiara;Yolken, Robert H.;Alaedini, Armin
通讯作者：
Alaedini, Armin