A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus

Lorraine A. Degiorgio, Konstantin N. Konstantinov, Sunhee C. Lee, John A. Hardin, Bruce T. Volpe, Betty Diamond

Research output: Contribution to journalArticle

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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 sub-units 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.

Original languageEnglish (US)
Pages (from-to)1189-1193
Number of pages5
JournalNature Medicine
Volume7
Issue number11
DOIs
StatePublished - 2001

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Antinuclear Antibodies
Glutamate Receptors
Systemic Lupus Erythematosus
Cerebrospinal fluid
N-Methyl-D-Aspartate Receptors
Cerebrospinal Fluid
Antibodies
DNA
Neurology
Viperidae
Neurons
Central Nervous System
Kidney

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Degiorgio, L. A., Konstantinov, K. N., Lee, S. C., Hardin, J. A., Volpe, B. T., & Diamond, B. (2001). A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nature Medicine, 7(11), 1189-1193. https://doi.org/10.1038/nm1101-1189

A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. / Degiorgio, Lorraine A.; Konstantinov, Konstantin N.; Lee, Sunhee C.; Hardin, John A.; Volpe, Bruce T.; Diamond, Betty.

In: Nature Medicine, Vol. 7, No. 11, 2001, p. 1189-1193.

Research output: Contribution to journalArticle

Degiorgio, LA, Konstantinov, KN, Lee, SC, Hardin, JA, Volpe, BT & Diamond, B 2001, 'A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus', Nature Medicine, vol. 7, no. 11, pp. 1189-1193. https://doi.org/10.1038/nm1101-1189
Degiorgio, Lorraine A. ; Konstantinov, Konstantin N. ; Lee, Sunhee C. ; Hardin, John A. ; Volpe, Bruce T. ; Diamond, Betty. / A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. In: Nature Medicine. 2001 ; Vol. 7, No. 11. pp. 1189-1193.
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