Brain-specific in the plasma Autoantibodies of subjects with autistic spectrum disorder

Brain-specific in the plasma Autoantibodies of subjects with autistic spectrum disorder
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DOI:
10.1196/annals.1381.010
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发表时间:
2007-01-01
期刊:
AUTOIMMUNITY, PT C
影响因子:
--
通讯作者:
de Water, Judy Van
de Water, Judy Van
中科院分区:
其他
文献类型:
--
作者:
Cabanlit, Maricel;Wills, Sharifia;de Water, Judy Van

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虽然自闭症谱系障碍(ASD)的诊断是基于行为参数,但一些研究已经报道了免疫系统异常,并提示自身免疫在ASD发病机制中的可能作用。在这项研究中,我们试图评估自闭症儿童(AU)血浆中脑特异性自身抗体的发生率,并与年龄匹配的对照组进行比较,包括无ASD的兄弟姐妹、典型发育(TD)对照组和其他发育障碍但非自闭症(DD)的儿童。172例患者(AU组,n = 63,中位年龄:43个月;TD组,n = 63,中位年龄:48个月;兄弟姐妹组,n = 25,中位年龄:61个月;DD组,n = 21,中位年龄:38个月)的血浆采用Western blot分析,检测针对成人大脑特定区域(包括下丘脑和丘脑)蛋白提取物的IgG抗体的存在。与TD对照组相比,在AU患者的血浆中检测到类似52 kDa MW的条带,其发生率显著高于TD对照组(分别在丘脑和下丘脑中为29%对8%,P = 0.0027和30%对11%,P = 0.01)。观察到对三种脑蛋白(42-48 kDa MW)的反应性,特别是在下丘脑,与13%的TD对照组相比,AU患者的发病率增加了37% (P = 0.004)。多种脑特异性自身抗体在AU患儿中出现的频率明显更高。虽然这些自身抗体在AU中的潜在作用目前尚不清楚,但它们的存在表明儿童早期对一种或多种神经抗原的自我耐受性丧失。
Although autism spectrum disorder (ASD) is diagnosed on the basis of behavioral parameters, several studies have reported immune system abnormalities and suggest the possible role of autoimmunity in the pathogenesis of ASD. In this study we sought to assess the incidence of brain-specific autoantibodies in the plasma of children with autism (AU) compared to age-matched controls including, siblings without ASD, typically developing (TD) controls, and children with other developmental disabilities, but not autism (DD). Plasma from 172 individuals (AU, n = 63, median age: 43 months; TD controls, n = 63, median age: 48 months; siblings, n = 25, median age: 61 months; and DD controls, n = 21, median age: 38 months) was analyzed by Western blot for the presence of IgG antibodies against protein extracts from specific regions of the human adult brain including the hypothalamus and thalamus. The presence of a similar to 52 kDa MW band, in the plasma of subjects with AU, was detected with a significantly higher incidence when compared to plasma from TD controls (29% vs. 8%, P = 0.0027 and 30% vs. 11%, P = 0.01, in the thalamus and hypothalamus, respectively). Reactivity to three brain proteins (42-48 kDa MW), in particular in the hypothalamus, were observed with increased incidence in 37% of subjects with AU compared to 13% TD controls (P = 0.004). Multiple brain-specific autoantibodies are present at significantly higher frequency in children with AU. While the potential role of these autoantibodies in AU is currently unknown, their presence suggests a loss of self-tolerance to one or more neural antigens during early childhood.