IMMUNOLOGY OF AUTISM

自闭症的免疫学

• 批准号: 6353038
• 负责人: REED P. WARREN
• 金额: $ 18.66万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353038
• 关键词: autism; clinical research; histocompatibility typing; human subject; hypogammaglobulinemia; immunoglobulin A; immunologic assay /test; immunologic memory; immunology; major histocompatibility complex; polymerase chain reaction; serotonin

Mounting evidence suggests that some autistic children may be susceptible to an environmental pathogen (most likely a virus or bacterium) resulting from an inherited deficiency of their immune system. Unable to clear the pathogen in a timely and normal fashion, the child would be at increased risk for the pathogen (or pathogenic toxins) to directly interfere with developing brain (or brain function) and/or lead to the generation of an autoimmune mechanism that interferes with brain functioning. Circumstantial evidence for this hypothesis stems from the number of features that autism shares with established immune and autoimmune disorders including: genetic predisposition; general immune imbalances; association with viral and other infections; demonstration of antibodies in the serum against proteins of the central nervous system and an uneven sex distribution. We have recently found additional evidence for the pathogen-autoimmune hypothesis for some cases of autism including an increased frequency of the C4B null allele and elevated representations of the extended haplotype B44-S30-DR4 and two DRbeta1 HVR-3 alleles. All of these genes are part of the major histocompatibility complex that exerts important control over immune function. This component focuses on several recently observed preliminary abnormalities that we have observed in autism which may be related to the WA genes. Findings obtained in this component also will be correlated with results obtained in the other components of this grant including stratification of autism by psychiatric, cognitive, neuroimaging and electroretinographic parameters. Specifically, this component will: perform HLA studies and determine C4 plasma levels on additional autistic and normal subjects; attempt to establish a possible relationship between the HLA system and elevated serotonin levels in autism; explore the basis of possible MHC- associated immunoglobulin IgA deficiency in some autistic subjects; attempt to confirm and expand studies on WA-restricted reactivity with cells of the autistic child by the maternal immune system.

越来越多的证据表明一些自闭症儿童可能是 容易受到环境病原体的影响（最有可能是病毒或 细菌）由于其免疫的遗传性不足而产生 系统。无法及时清除病原体， 孩子的病原体（或致病性）的风险会增加 毒素）直接干扰发展的大脑（或大脑功能） 和/或导致产生一种自身免疫机制 干扰大脑功能。间接证据 假设源于自闭症与 已建立的免疫和自身免疫性疾病，包括：遗传 倾向；一般免疫失衡；与病毒和 其他感染；表现出抗体中抗体的抗体 中枢神经系统的蛋白质和性别分布不均匀。 我们最近发现了病原体 - 自由免疫的其他证据 在某些自闭症情况下的假设，包括增加频率 C4B无效等位基因和延长的高度表示 单倍型B44-S30-DR4和两个DRBETA1 HVR-3等位基因。所有这些基因 是主要的组织相容性复合物的一部分 控制免疫功能。该组件侧重于几个 最近观察到我们在 可能与WA基因有关的自闭症。在此获得的发现 组件也将与在另一个中获得的结果相关 这笔赠款的组成部分，包括自闭症分层 精神病，认知，神经影像学和电图学 参数。具体而言，该组成部分将：进行HLA研究和 确定其他自闭症和正常受试者的C4血浆水平； 试图在HLA系统和 自闭症中的5-羟色胺水平升高；探索可能的MHC-的基础 某些自闭症患者中相关的免疫球蛋白IgA缺乏； 试图确认和扩展对WA限制反应性的研究 母体免疫系统的自闭症儿童细胞。