FAULTY IMMUNE REGULATION IN AUTISM

自闭症患者的免疫调节错误

• 批准号: 2245347
• 负责人: REED P. WARREN
• 金额: $ 11.47万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2245347
• 关键词: CD antigens; alleles; antibody formation; autoantibody; autoimmune disorder; brain; child (0-11); complement; early infantile autism; enzyme linked immunosorbent assay; flow cytometry; genetic markers; histocompatibility typing; human subject; immunogenetics; laboratory mouse; major histocompatibility complex; monocyte; myelin basic proteins; myelination; natural killer cells; polymerase chain reaction; serotonin receptor; suppressor T lymphocyte; tissue /cell culture; western blottings

Autism is a severe developmental disorder characterized by abnormalities in the manner in which the brain collects and integrates information resulting in abnormal communication and social skills. Currently, there is no known single cause for autism; however, recent investigations suggest that autism has a biological basis and results from a combination of factors including genetic, immunologic, viral or other. Several recent immunogenetic and immunoregulatory findings, in our laboratory and elsewhere, suggest that some cases of autism may result from an autoimmune mechanism. Moreover, autism expresses several disease characteristics as seen in known autoimmune disorders such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. This project will attempt to gain concrete evidence for or against the existence of autoimmune mechanisms in autism. This renewal proposal has four specific aims: (1) a confirmation and expansion of studies of a recent exciting finding that we have made on an association of the extended major histocompatibility complex (MHC) complex and the C4B null (QO) allele with autism. Most autoimmune disorders are associated with the MHC and several autoimmune diseases are associated with null alleles of the C4 complement loci;(2) an investigation of the basis and relevance of abnormal immune regulatory function in autistic children with the results being compared with those from healthy subjects and subjects with idiopathic mental retardation; (3) a study of in vitro antibody production and suppressor T cell regulation; and (4) an exploration of the sera of autistic subjects for specific autoantibodies against the brain-tissue antigens myelin basic protein, serotonin receptor and neuron-axon filament proteins. The proposed studies may firmly establish a biological correlate or marker for autism and, hopefully, lead to eventual therapeutic intervention with immunomodulating agents for this severe disorder.

自闭症是一种严重的发育障碍，其特征是 大脑收集和 整合导致异常沟通和的信息 社交技能。 目前，没有已知的单一原因 自闭症；但是，最近的调查表明自闭症具有 生物学基础和来自多种因素的结果 包括遗传，免疫学，病毒或其他。 最近的几个 在我们的实验室和 在其他地方，建议某些自闭症病例可能是由 自身免疫机制。 此外，自闭症表达了几种疾病 在已知的自身免疫性疾病中看到的特征，例如 多发性硬化症，类风湿关节炎和全身性狼疮 红斑。 该项目将尝试获得具体的证据 用于自闭症中自身免疫机制或反对或反对。 该续订提案具有四个具体目标：（1）确认 并扩展了我们最近有一个令人兴奋的发现的研究 建立在扩展的主要组织兼容性的关联上 复合物（MHC）复合物和自闭症的C4B NULL（QO）等位基因。 大多数自身免疫性疾病与MHC相关，几个 自身免疫性疾病与C4的无效等位基因有关 补充基因座；（2）调查的基础和相关性 自闭症儿童的免疫调节功能异常 将结果与健康受试者和 特发性智力低下的受试者； （3）一项研究 体外抗体产生和抑制T细胞调节；和 （4）探索特定自闭症学科的血清 针对脑组织抗原髓磷脂的自身抗体基本 蛋白质，5-羟色胺受体和神经元 - 轴突丝蛋白。 拟议的研究可能会牢固建立生物学相关性 或自闭症的标记，希望最终导致治疗 对这种严重疾病的免疫调节剂的干预。