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
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
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.