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| Item Type: | Article |
|---|---|
| Title: | Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis |
| Creators Name: | Matus, S., Burgos, P.V., Bravo-Zehnder, M., Kraft, R., Porras, O.H., Farias, P., Barros, L.F., Torrealba, F., Massardo, L., Jacobelli, S. and Gonzalez, A. |
| 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. |
| 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 |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 204 |
| Number: | 13 |
| Page Range: | 3221-3234 |
| Date: | 24 December 2007 |
| Official Publication: | https://doi.org/10.1084/jem.20071285 |
| PubMed: | View item in PubMed |
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