Autism-specific maternal autoantibodies recognize critical proteins in developing brain.
Autism-specific maternal autoantibodies recognize critical proteins in developing brain.
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DOI：
10.1038/tp.2013.50
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发表时间：
2013-07-09
影响因子：
6.8
通讯作者：
Van de Water J
中科院分区：
文献类型：
--
作者：
Braunschweig D;Krakowiak P;Duncanson P;Boyce R;Hansen RL;Ashwood P;Hertz-Picciotto I;Pessah IN;Van de Water J
自闭症谱系障碍（ASD）起源于神经发育，在美国估计每88名儿童中就有1名受到影响。我们先前描述了ASD特异性母体自身抗体，识别胎儿脑抗原。在此，我们证明，乳酸脱氢酶A和B（LDH），cypin，应激诱导的磷蛋白1（STIP 1），胰蛋白酶反应介导蛋白1和2（CRMP 1，CRMP 2）和Y-盒结合蛋白，包括母体自身抗体相关（MAR）自闭症的七个主要抗原。在23%的ASD儿童母亲和仅1%的对照组中注意到对特异性抗原组合的排他性反应。母亲对LDH、STIP 1和CRMP 1和/或cypin具有特异性反应性的ASD儿童（7% vs对照组0%; P<0.0002;比值比为24.2（95%置信区间：1.45-405））与母亲缺乏这些抗体的ASD儿童相比，具有更高的刻板行为。我们描述了第一组具有临床意义的生物标志物，其对自闭症风险的特异性超过99%，从而促进了我们对MAR自闭症的病因机制和治疗可能性的理解。
Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45–405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.