Day :
Keynote Forum
Czeslawa Kowal,
The Feinstein Institute for Medical Research, USA
Keynote: Anti-NMDA Receptor Antibodies and CNS Lupus
Time : 11:50-12:30
Biography:
Czeslawa Kowal completed her PhD in the Institute of Organic Chemistry of the Polish Academy of Sciences, Warsaw, Poland, and her postdoctoral training in molecular biology and in immunology at Columbia University and at the Albert Einstein College of Medicine New York. She has published 45 peer reviewed papers and book chapters in reputed journals. She is a member of the American Association of Immunologists.
Abstract:
Lupus is an autoimmune disease affecting primarily women in child bearing age. It is a multiorgan involvement disease, with frequent central nervous system (CNS) manifestation, most particularly, cognitive impairment. Lupus is characterized by the production of antinuclear autoantibodies and in particular, anti-dsDNA antibodies. We have created an animal model of CNS lupus in which autoantibodies cross-reactive with dsDNA and with the NMDA receptor (NMDAR) lead to an enhanced NMDAR activation and, at higher concentration to neuronal death when present in the brain parenchyma. We have shown that this requires breaching of the blood brain barrier. We have further demonstrated in the mouse model that the impact of these antibodies on neurons was concentration dependent and that at higher concentration, these antibodies promote neuronal excitotoxicity through enhanced mitochondrial permeability transition. In the model spatial recognition deficits are caused by the presence of these antibodies in the hippocampus. Structural analysis revealed a substantial reduction in dendritic processes and spines accompanied by a significant expansion of a place field size of surviving CA1 pyramidal. We and others have shown that the presence of these antibodies in the cerebrospinal fluid of lupus patients correlates with diffuse manifestations of CNS lupus. Recent studies of lupus patients harboring dsDNA and NMDAR reactive antibodies demonstrate an association with an impairment in spatial memory. This observation is in striking similarity to the mouse model.