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- Title
Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus.
- Authors
Lee, Ji Y; Huerta, Patricio T; Zhang, Jie; Kowal, Czeslawa; Bertini, Eva; Volpe, Bruce T; Diamond, Betty
- Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by autoantibodies and preferentially affecting women of childbearing age. Because the offspring of mothers with SLE show a high frequency of learning disorders, we hypothesized that maternally transferred autoantibodies that bind DNA and the N-methyl-D-aspartate receptor (NMDAR) could have a pathogenic role during fetal brain development. Here we describe a maternal SLE mouse model wherein pregnant dams harbored DNA-specific, NMDAR-specific autoantibodies throughout gestation. High titers of these autoantibodies 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 autoantibodies causes abnormal brain development with long-term consequences. This paradigm may apply to multiple congenital neuropsychiatric disorders.
- Publication
Nature medicine, 2009, Vol 15, Issue 1, p91
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.1892