A Subset of Lupus anti-DNA Antibodies Cross-Reacts With the NR2 Glutamate Receptor in Systemic Lupus Erythematosus

Nat Med. 2001 Nov;7(11):1189-93. doi: 10.1038/nm1101-1189.

Abstract

In systemic lupus erythematosus, antibodies against double-stranded DNA are a major contributor to renal disease. We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA. This sequence is also present in the extracellular domain of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a and NR2b. Here we show that the NR2 receptor is recognized by both murine and human anti-DNA antibodies. Moreover, anti-DNA antibodies with this cross-reactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus erythematosus contains these antibodies and also mediates neuronal death via an apoptotic pathway. These observations indicate that lupus antibodies cross-react with DNA and NMDA receptors, gain access to cerebrospinal fluid and may mediate non-thrombotic and non-vasculitic abnormalities of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / cerebrospinal fluid
  • Antibodies, Antinuclear / immunology*
  • Apoptosis
  • Cells, Cultured
  • Cross Reactions
  • Humans
  • In Vitro Techniques
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / immunology
  • Neurons / pathology
  • Receptors, N-Methyl-D-Aspartate / immunology*

Substances

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