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

Citation
La. Degiorgio et al., A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus, NAT MED, 7(11), 2001, pp. 1189-1193
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
1078-8956 → ACNP
Volume
7
Issue
11
Year of publication
2001
Pages
1189 - 1193
Database
ISI
SICI code
1078-8956(200111)7:11<1189:ASOLAA>2.0.ZU;2-S
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-TrpAsp/Glu-Tyr-Ser/Gly is a molecular mimic of do uble-stranded DNA. This sequence is also present in the extracellular domai n of murine and human NMDA (N-methyl-D-aspartate) receptor subunits NR2a an d 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-r eactivity mediate apoptotic death of neurons in vivo and in vitro. Finally, we show that the cerebrospinal fluid of a patient with systemic lupus eryt hematosus 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.