Coutinho Ester, Jacobson Leslie, Pedersen Marianne Giørtz, Benros Michael Eriksen, Nørgaard-Pedersen Bent, Mortensen Preben Bo, Harrison Paul J, Vincent Angela
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Department of Economics and Business Economics, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
J Neurol Neurosurg Psychiatry. 2017 Sep;88(9):718-721. doi: 10.1136/jnnp-2016-315251. Epub 2017 Jun 1.
BACKGROUND, METHODS AND OBJECTIVES: Maternal autoantibodies to neuronal proteins may be one cause of neurodevelopmental disorders. This exploratory study used the Danish archived midgestational sera and their nationwide registers to search for antibodies to the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein-like 2 (CASPR2) in maternal sera, and to relate them to subsequent psychiatric diagnoses in the woman or her child.
In a sample of 192 women, there was no association between antibody status and subsequent psychosis in the mothers. However, NMDAR antibodies (n=4) or CASPR2 antibodies (n=1) were identified in 5/11 (45.5%) women whose children were given a diagnosis of mild or unspecified mental retardation or disorders of psychological and motor development (collectively abbreviated as mental retardation and/or disorders of psychological development (MR/DPD)) compared with 9/176 (5.1%) of the remaining mother (p<0.001). These findings were followed up in a specifically selected cohort, in which CASPR2 antibodies were detected in 7/171 (4.1%) mothers of MR/DPD progeny, compared with only 1/171 (0.6%) control mother (p=0.067). The combined sample showed a significantly higher frequency of CASPR2 antibodies in mothers of MD/DPD children (p=0.01). These autoantibodies were not increased in mothers of children with autistic spectrum disorder.
These findings complement the known roles of CASPR2 in brain development, and warrant further epidemiological and experimental studies to clarify the role of CASPR2 and possibly other antibodies in neurodevelopmental disorders.
背景、方法与目的：母体针对神经元蛋白的自身抗体可能是神经发育障碍的原因之一。这项探索性研究利用丹麦存档的孕中期血清及其全国登记系统，在母体血清中寻找针对N-甲基-D-天冬氨酸受体（NMDAR）和接触蛋白相关蛋白样2（CASPR2）的抗体，并将其与女性自身或其子女随后的精神疾病诊断相关联。
在192名女性样本中，抗体状态与母亲随后的精神病之间没有关联。然而，在其子女被诊断为轻度或未明确的智力发育迟缓或心理与运动发育障碍（统称为智力发育迟缓及/或心理发育障碍（MR/DPD））的11名女性中，有5名（45.5%）检测到NMDAR抗体（n = 4）或CASPR2抗体（n = 1），而其余母亲中有9名（5.1%）检测到此类抗体（p<0.001）。在一个专门挑选的队列中对这些发现进行了随访，其中在MR/DPD后代的171名母亲中有7名（4.1%）检测到CASPR2抗体，而对照母亲中只有1名（0.6%）检测到（p = 0.067）。合并样本显示，MR/DPD儿童的母亲中CASPR2抗体的频率显著更高（p = 0.01）。自闭症谱系障碍儿童的母亲中这些自身抗体并未增加。
这些发现补充了CASPR2在大脑发育中的已知作用，有必要进行进一步的流行病学和实验研究，以阐明CASPR2以及可能的其他抗体在神经发育障碍中的作用。
