title: Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus.
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.
authors.affiliation: Albert Einstein College of Medicine, Department of Microbiology & Immunology, Bronx, NY 10461, USA.
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Patricio T
authors.initials: PT
authors.lastname: Huerta
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Czeslawa
authors.initials: C
authors.lastname: Kowal
authors.forename: Eva
authors.initials: E
authors.lastname: Bertini
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D003603:Cytotoxins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology*; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009421:Nervous System Malformations / Q000209:etiology* / Q000276:immunology; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D003603:Cytotoxins; D016194:Receptors, N-Methyl-D-Aspartate