Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis
Item Type: | Article |
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Title: | Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis |
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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. |
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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. |
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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 |
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Source: | Journal of Experimental Medicine |
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ISSN: | 0022-1007 |
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Publisher: | Rockefeller University Press |
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Volume: | 204 |
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Number: | 13 |
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Page Range: | 3221-3234 |
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Date: | 24 December 2007 |
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Official Publication: | https://doi.org/10.1084/jem.20071285 |
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PubMed: | View item in PubMed |
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