FAULTY MATERNAL-FETAL IMMUNE REGULATION IN AUTISM

自闭症母体-胎儿免疫调节缺陷

• 批准号: 3381161
• 负责人: REED P. WARREN
• 金额: $ 27.56万
• 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 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381161
• 关键词: T lymphocyte; autism; behavior disorders; blocking antibody; brain; cell mediated cytotoxicity; child (0-11); complement pathway; density gradient ultracentrifugation; flow cytometry; human subject; immunogenetics; immunologic assay /test; immunopathology; leukocyte antigen typing; mixed lymphocyte reaction test; pregnancy disorder; pregnancy immunology; radiotracer; suppressor T lymphocyte

Several recent immunogenetic and clinical findings suggest a pathogenic relationship between autism and faulty immune regulation. The long-term objective of this project is an attempt to provide compelling evidence for or against the idea that unregulated immune processes create a specific brain lesion resulting in autism. The immediate objectives are to search for evidence that faulty maternal-fetal immune regulation is associated with autism and that such impaired regulation allows maternal immune elements to exist which have the potential to create brain lesions. An additional current objective is to determine the mechanistic basis of abnormal immune function of children with autism. The specific aims are: 1. study sharing of genetically-determined human leukocyte antigens (HLA) and extended haplotypes by parents of autistic children and attempt to determine if any HLA antigen or extended haplotype is associated with autism; 2. investigate the bases of abnormal T-cell function in mothers of autistic children using the T-cell blastogenesis assay, the interleukin assays and lymphocyte enumeration; 3. search for a lack of blocking factors in the sera of mothers of autistic children using the mixed lymphocyte culture assay; 4. explore maternal immunity against lymphocyte antigens of the autistic child, father and other children in the family using the antibody-dependent cell-mediated cytotoxicity assay and the complement-dependent cytotoxicity assay; 5. study the ability of OKT4+ suppressor T- cells in patients with autism to block antibody production by maternal lymphocytes, and 6. extend studies on abnormal T-cell immunity and natural killer cell activity in autistic patients.

最近的一些免疫遗传和临床发现表明 自闭症与免疫失调之间的致病关系 规定。 该项目的长期目标是尝试 提供令人信服的证据或反对以下想法 不受管制的免疫过程会产生特定的脑病变 导致自闭症。 直接的目标是搜索 证据表明孕产妇免疫调节错误是 与自闭症相关，这种监管受损允许 孕产妇的免疫元素存在可能 创建脑部病变。 目前的另一个目标是 确定异常免疫功能的机理基础 自闭症儿童。 具体目的是：1。遗传确定的研究共享 人类白细胞抗原（HLA）和扩展单倍型 自闭症儿童的父母，并试图确定是否有HLA 抗原或扩展单倍型与自闭症有关； 2。 研究母亲中T细胞功能异常的基础 使用T细胞囊泡分析的自闭症儿童， 白介素分析和淋巴细胞列出； 3。搜索 自闭症儿童母亲的血清缺乏阻塞因素 使用混合淋巴细胞培养试验； 4。探索产妇 对自闭症儿童的淋巴细胞抗原的免疫力，父亲 和家庭中的其他儿童使用抗体依赖性 细胞介导的细胞毒性测定和补体依赖性 细胞毒性测定； 5。研究Okt4+抑制剂T-的能力 自闭症患者的细胞通过 母体淋巴细胞和6。扩展了异常T细胞的研究 自闭症患者的免疫力和天然杀伤细胞活性。