title: A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus.
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.
authors.affiliation: Department of Neurology & Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, New York, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: DeGiorgio
authors.forename: K N
authors.initials: KN
authors.lastname: Konstantinov
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: J A
authors.initials: JA
authors.lastname: Hardin
authors.forename: B T
authors.initials: BT
authors.lastname: Volpe
authors.forename: B
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000134:cerebrospinal fluid / Q000276:immunology*; D017209:Apoptosis; D002478:Cells, Cultured; D003429:Cross Reactions; D006801:Humans; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000276:immunology / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D016194:Receptors, N-Methyl-D-Aspartate