Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, United States.
Brain Behav Immun. 2011 Mar;25(3):514-23. doi: 10.1016/j.bbi.2010.11.017. Epub 2010 Dec 4.
Autism is a heterogeneous disorder with a poorly understood biological basis. Some children with autism harbor plasma autoantibodies that target brain proteins. Similarly, some mothers of children with autism produce antibodies specific to autism that target pairs of fetal brain proteins at 37/73 and 39/73 kDa. We explored the relationship between the presence of brain-specific autoantibodies and several behavioral characteristics of autism in 277 children with an autism spectrum disorder and 189 typically developing age-matched controls. Further, we used maternal autoantibody data to investigate potential familial relationships for the production of brain-directed autoantibodies. We demonstrated by Western blot that autoantibodies specific for a 45 kDa cerebellar protein in children were associated with a diagnosis of autism (p=0.017) while autoantibodies directed towards a 62 kDa protein were associated with the broader diagnosis of autism spectrum disorder (ASD) (p=0.043). Children with such autoantibodies had lower adaptive (p=0.0008) and cognitive function (p=0.005), as well as increased aberrant behaviors (p<0.05) compared to children without these antibodies. No correlation was noted for those mothers with the most specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62 kDa bands. Collectively, these data suggest that antibodies towards brain proteins in children are associated with lower adaptive and cognitive function as well as core behaviors associated with autism. It is unclear whether these antibodies have direct pathologic significance, or if they are merely a response to previous injury. Future studies are needed to determine the identities of the protein targets and explore their significance in autism.
自闭症是一种具有复杂生物学基础且表现多样的疾病。一些自闭症患儿的血浆中存在针对脑部蛋白的自身抗体。同样，一些自闭症患儿的母亲会产生针对自闭症的特异性抗体，这些抗体能识别胎脑蛋白中的一对分子量分别为 37/73 和 39/73kDa 的蛋白。我们通过对 277 名自闭症谱系障碍患儿和 189 名年龄匹配的正常发育对照者进行研究，探究了脑部特异性自身抗体的存在与自闭症几种行为特征之间的关系。此外，我们还利用母亲的自身抗体数据，调查了产生脑部靶向自身抗体的潜在家族关系。我们通过 Western blot 证实，患儿中针对小脑 45kDa 蛋白的特异性自身抗体与自闭症的诊断相关（p=0.017），而针对 62kDa 蛋白的自身抗体与更广泛的自闭症谱系障碍（ASD）诊断相关（p=0.043）。与没有这些抗体的患儿相比，具有此类抗体的患儿的适应性（p=0.0008）和认知功能（p=0.005）较低，且异常行为增加（p<0.05）。我们未发现具有最特异的抗胎儿脑自身抗体模式的母亲与具有 45 或 62kDa 条带自身抗体的患儿之间存在相关性。综合这些数据表明，患儿针对脑部蛋白的自身抗体与较低的适应性和认知功能以及与自闭症相关的核心行为有关。这些抗体是否具有直接的病理意义，或者它们是否仅仅是对先前损伤的反应，目前还不清楚。未来的研究需要确定蛋白靶标的身份，并探讨其在自闭症中的意义。
