This is a application to study the contribution of a particular autoantibody to aspects of neuropsychiatric lupus. Four proposed research projects derive from the observation that a subset of anti-DNA antibodies present in the serum of lupus patients cross-reacts with NMDA receptors (NMDARs) and is capable of mediating apoptotic death of neurons leading to hippocampal (cognitive) or amygdale (behavioral) impairment. The immediate goals of the Program are four-fold;each goal is addressed in a specific project: Project 1: to determine whether there is variability in the electrophysiologic signature of monoclonal antibodies to the NMDAR corresponding with functional variability;Project 2: to determine whether maternal antibodies to the NMDAR cause impairment in fetal brain development;Project 3: to determine if antibody-mediated impairment of the hippocampus or amygdala can be detected by functional magnetic resonance imaging in patients with lupus and Project 4: to determine whether we can develop therapeutic strategies for neuroprotection. The Program includes an Administrative Core with an Advisory Committee to facilitate the research agenda. There is a Behavior Core, a Histology Core and a Monoclonal Antibody Core to provide high quality, uniform quality immunohistology and behavioral analysis as well as standardized batches of monoclonal anti-NMDAR antibodies for Projects 1, 2 and 4. This Program represents a multidisciplinary approach to a perplexing and disabling problem in patients with systemic lupus. The investigators have track records of productivity and collaborative interactions that ensure the success of this endeavor.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-KS-I (J1))
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Johnson, David R
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Feinstein Institute for Medical Research
United States
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