Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus.
Ji Y Lee, Patricio T Huerta, Jie Zhang, Czeslawa Kowal, Eva Bertini, Bruce T Volpe, Betty Diamond
Albert Einstein College of Medicine, Department of Microbiology & Immunology, Bronx, NY 10461, USA.
Nature medicine 2009 Jan
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.
Citation
Ji Y Lee, Patricio T Huerta, Jie Zhang, Czeslawa Kowal, Eva Bertini, Bruce T Volpe, Betty Diamond. Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus. Nature medicine. 2009 Jan;15(1): 91-6
PMID: 19079257
View Free Full Text