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Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis

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Official URL:https://doi.org/10.1084/jem.20071285
PubMed:View item in PubMed
Creators Name:Matus, S. and Burgos, P.V. and Bravo-Zehnder, M. and Kraft, R. and Porras, O.H. and Farias, P. and Barros, L.F. and Torrealba, F. and Massardo, L. and Jacobelli, S. and Gonzalez, A.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Page Range:3221-3234
Date:24 December 2007
Keywords:Apoptosis, Autoantibodies, Biological Models, Brain, Calcium, Cell Membrane, Central Nervous System, Central Nervous System Lupus Vasculitis, Epitopes, Neurons, Peptides, Proteins, Ribosomes, Synaptosomes, Animals, Rats
Abstract:The interesting observation was made 20 years ago that psychotic manifestations in patients with systemic lupus erythematosus are associated with the production of antiribosomal-P protein (anti-P) autoantibodies. Since then, the pathogenic role of anti-P antibodies has attracted considerable attention, giving rise to long-term controversies as evidence has either contradicted or confirmed their clinical association with lupus psychosis. Furthermore, a plausible mechanism supporting an anti-P-mediated neuronal dysfunction is still lacking. We show that anti-P antibodies recognize a new integral membrane protein of the neuronal cell surface. In the brain, this neuronal surface P antigen (NSPA) is preferentially distributed in areas involved in memory, cognition, and emotion. When added to brain cellular cultures, anti-P antibodies caused a rapid and sustained increase in calcium influx in neurons, resulting in apoptotic cell death. In contrast, astrocytes, which do not express NSPA, were not affected. Injection of anti-P antibodies into the brain of living rats also triggered neuronal death by apoptosis. These results demonstrate a neuropathogenic potential of anti-P antibodies and contribute a mechanistic basis for psychiatric lupus. They also provide a molecular target for future exploration of this and other psychiatric diseases.
Publisher:Rockefeller University Press (U.S.A.)
Item Type:Article

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