Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions.
Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions.
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DOI：
10.1002/aur.1657
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发表时间：
2017-01
期刊：
影响因子：
4.7
通讯作者：
Van de Water, Judy
中科院分区：
文献类型：
--
作者：
Krakowiak, Paula;Walker, Cheryl K.;Tancredi, Daniel;Hertz-Picciotto, Irva;Van de Water, Judy
关键词：
大约23%的自闭症谱系障碍（ASD）儿童的母亲会产生针对胎儿脑组织的特定抗体模式，而只有1%的正常发育儿童的母亲会检测到这种抗体模式。然而，目前尚不清楚是什么原因导致这些ASD特异性抗胎儿抗体的产生。我们在227名2-5岁ASD儿童的母亲中检查了ASD特异性抗胎儿抗体与妊娠期间代谢状况之间的关系，这些母亲参加了CHARGE（遗传学和环境导致的儿童自闭症风险）研究，并在研究登记后测量了这些抗胎儿脑抗体的血液样本。代谢疾病包括糖尿病、高血压疾病和孕前肥胖或超重。与健康母亲相比，ASD特异性抗胎儿脑抗体模式在妊娠期间诊断为糖尿病、高血压疾病或超重的母亲中更常见，但这些差异未达到统计学显著性。在145名儿童表现出严重ASD症状的母亲的子集中，与健康母亲相比，被诊断患有2型或妊娠糖尿病的母亲有ASD特异性抗胎儿抗体的可能性高出近3倍。此外，那些被诊断患有妊娠期糖尿病的人有超过3倍的可能性具有这些抗胎儿脑抗体。在这项探索性研究中，孩子患有严重ASD和被诊断患有糖尿病的母亲更有可能在2-5年后产生抗胎儿脑自身抗体。大约23%的自闭症谱系障碍（ASD）儿童的母亲会产生针对胎儿脑蛋白的特定模式的自身抗体，而在正常发育儿童的母亲中仅检测到1%。ASD特异性母体自身抗体的生物学机制尚不清楚。我们试图确定ASD特异性母体自身抗体是否与妊娠期间的代谢状况（MC）有关。参与者是227名2-5岁确诊ASD儿童的母亲，在2003年1月至2008年4月期间参加了CHARGE（遗传学和环境引起的儿童自闭症风险），并收集了血液样本并分析了抗胎儿脑自身抗体（Ab+）。MC包括糖尿病，高血压疾病，孕前肥胖或超重，从医疗记录或结构化的电话采访中确定。对数线性回归模型进行估计患病率比（PR）和95%的置信区间（CI）的基础上稳健的标准误差。五十六例（25%）母亲为Ab+。与健康母亲相比，患有糖尿病、高血压疾病或超重的母亲的Ab+患病率较高，但差异无统计学意义。在145名母亲的一个子集中，其子女表现出严重的ASD（31 Ab+），那些被诊断为2型或妊娠期糖尿病的母亲是Ab+的可能性的2.7倍（95% CI 1.1，6.6），控制交付付款人和吸烟。特别是糖尿病与Ab+患病率增加3.2倍相关（95% CI 1.2，8.6）。在这项探索性研究中，患有严重ASD和糖尿病的孩子的母亲更有可能在2-5年后产生抗胎儿脑自身抗体。
Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of antibodies to fetal brain tissue that have been detected in only 1% of mothers of typically developing children. However, it is unknown what causes these ASD-specific anti-fetal antibodies to be produced. We examined the relationship between ASD-specific anti-fetal antibodies and metabolic conditions during pregnancy in 227 mothers of 2–5 year old children with ASD, enrolled in the CHARGE (Childhood Autism Risk from Genetics and the Environment) Study, and who had blood samples measured for these anti-fetal brain antibodies after study enrollment. Metabolic conditions included diabetes, hypertensive disorders, and prepregnancy obesity or overweight. The presence of ASD-specific anti-fetal brain antibody patterns was more common among mothers diagnosed with diabetes, hypertensive disorders, or overweight during pregnancy compared to healthy mothers, but these differences did not reach statistical significance. In a subset of 145 mothers whose children exhibited severe ASD symptoms, those diagnosed with type 2 or gestational diabetes were nearly 3 times more likely to have ASD-specific anti-fetal antibodies compared to healthy mothers. Further, those diagnosed with gestational diabetes specifically were over 3 times more likely to have these anti-fetal brain antibodies. In this exploratory study, mothers whose children had severe ASD and who were diagnosed with diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later. Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD-specific maternal autoantibodies are poorly understood. We sought to determine whether ASD-specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2–5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti-fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log-linear regression models were performed to estimate prevalence ratios (PR) and 95% confidence intervals (CI) based on robust standard errors. Fifty-six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7-fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2-fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later.
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影响因子：
3.9
作者：
Gotham, Katherine;Pickles, Andrew;Lord, Catherine
通讯作者：
Lord, Catherine
DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
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通讯作者：
Van de Water J
影响因子：
4.7
作者：
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影响因子：
4.7
作者：
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Levitt, Pat