Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus

Nat Med. 2009 Jan;15(1):91-6. doi: 10.1038/nm.1892. Epub 2008 Dec 14.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Cytotoxins / immunology
  • Disease Models, Animal
  • Female
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology*
  • Maternal-Fetal Exchange / immunology
  • Mice
  • Mice, Inbred BALB C
  • Nervous System Malformations / etiology*
  • Nervous System Malformations / immunology
  • Neurons / immunology*
  • Neurons / metabolism
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / immunology*
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Antibodies, Antinuclear
  • Autoantibodies
  • Cytotoxins
  • Receptors, N-Methyl-D-Aspartate