Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus.
Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus.
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系统性红斑狼疮(SLE)是一种由自身抗体(AABS)介导的、好发于育龄妇女的自身免疫性疾病。由于SLE母亲的后代表现出高频率的学习障碍，我们假设母亲转移的结合DNA和N-甲基-D-天冬氨酸受体(NMDAR)的AABS可能在胎儿大脑发育过程中发挥致病作用。在这里，我们描述了一种母体系统性红斑狼疮小鼠模型，在该模型中，怀孕的母鼠在整个妊娠过程中都携带有DNA特异的、NMDAR特异的AABS。母体循环中这些AABS的高滴度会导致胎儿大脑的组织学异常，并随后导致成年后代的认知障碍。这些数据支持这样一种范式，即在宫内暴露于神经毒性AABS会导致大脑发育异常，并产生长期后果。这一范例可能适用于多发性先天性神经精神障碍。
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by autoantibodies (AAbs) and preferentially affecting women of childbearing age. Since the offspring of mothers with SLE exhibit a high frequency of learning disorders, we hypothesized that maternally transferred AAbs that bind DNA and the N-methyl-D-aspartate receptor (NMDAR) could play a pathogenic role during fetal brain development. Here we describe a maternal SLE murine model wherein pregnant dams harbored DNA-specific, NMDAR-specific AAbs throughout gestation. High titers of these AAbs in maternal circulation led to histological abnormalities in fetal brain and subsequent cognitive impairments in adult offspring. These data support a paradigm in which in utero exposure to neurotoxic AAbs causes abnormal brain development with long-term consequences. This paradigm may apply to multiple congenital neuropsychiatric disorders.
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双链DNA（DSDNA）的肽替代物免疫可诱导自身抗体的产生和肾脏免疫球蛋白沉积。
影响因子：
15.3
作者：
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通讯作者：
Diamond, B
影响因子：
5.1
作者：
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通讯作者：
Mellgren, SI
DOI：
10.1016/s0165-3806(01)00126-2
发表时间：
2001-04-30
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Ritter, LM;Unis, AS;Meador-Woodruff, JH
通讯作者：
Meador-Woodruff, JH
影响因子：
--
作者：
Ross, G;Sammaritano, L;Lockshin, M
通讯作者：
Lockshin, M
DOI：
10.1073/pnas.0608397104
发表时间：
2006-12-26
影响因子：
11.1
作者：
Kowal, Czeslawa;DeGiorgio, Lorraine A.;Diamond, Betty
通讯作者：
Diamond, Betty