title: Female mouse fetal loss mediated by maternal autoantibody.
abstract: Systemic lupus erythematosus (SLE), a disease of women during childbearing years, is characterized by the production of double-stranded DNA antibodies. A subset of these antibodies, present in 40% of patients, cross-reacts with the NR2A and NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR). In this study, we show that, in mouse models, these antibodies cause a loss of female fetus viability by inducing apoptosis of NR2A-expressing neurons within the brainstem late in fetal development; gender specificity derives from a time-dependent increased expression of NR2A in female brainstem or increased vulnerability of female fetal neurons to signaling through NR2A-containing NMDARs. This paradigm is consistent with available data on the sex ratio of live births of women with SLE. It represents a novel mechanism by which maternal autoantibodies can severely affect fetal health in a gender-specific fashion and raises the question of how many maternal antibodies affect brain development or exhibit gender-specific fetal effects.
authors.affiliation: Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, NorthShore–Long Island Jewish Health System, Manhasset, NY 11030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Dun
authors.initials: D
authors.lastname: Zhou
authors.forename: Ji
authors.initials: J
authors.lastname: Lee
authors.forename: Haitao
authors.initials: H
authors.lastname: Niu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Faust
authors.forename: Stephen
authors.initials: S
authors.lastname: Frattini
authors.forename: Czeslawa
authors.initials: C
authors.lastname: Kowal
authors.forename: Patricio T
authors.initials: PT
authors.lastname: Huerta
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001921:Brain / Q000196:embryology* / Q000473:pathology; D005260:Female; D005313:Fetal Death / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012737:Sex Factors; D012744:Sex Ratio
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; C526794:aspartyl-tryptophyl-glutamyl-tyrosyl-seryl-valyl-tryptophyl-leucyl-seryl-asparagine