Encephalitis is an inflammatory disease of the brain caused by infection or autoimmune conditions. The most common type of autoimmune encephalitis (AE) is associated with high titers of antibodies against N-methyl-D- aspartate type glutamate receptors (NMDARs), termed ?NMDAR-AE. Anti-NMDAR antibodies bind, cross-link, and internalize NMDAR receptors leading to altered neuronal function. Removal of anti-NMDAR antibodies has thus been the focus of first-line therapy, but recurrent attacks occur even in treated patients. Anti-NMDAR antibodies are produced by antibody secreting cells (ASCs), which arise from the memory B cell pool. We hypothesize that memory B cells and ASCs of ?NMDAR-AE patients express antibodies that bind to NMDARs. Establishing that the memory B cell pool of ?NMDAR-AE patients harbors a high frequency of NMDAR-reactive memory B cells would be the first step towards understanding the immunopathogenesis of ?NMDAR-AE, and may prompt consideration of additive therapies that would effectively remove NMDAR- reactive memory B cells early in the treatment and management of ?NMDAR-AE patients.
Patients with the most common form of autoimmune encephalitis make proteins called antibodies that bind to neurons and interfere with normal neuron function. Antibodies are made by specialized cells of the immune system called B cells. Our goal for this project is to identify the stage of development at which B cells make antibodies to neurons, and evaluate whether this information can help us understand how the disease develops.
| Venkatesan, Arun; Adatia, Krishma (2017) Anti-NMDA-Receptor Encephalitis: From Bench to Clinic. ACS Chem Neurosci 8:2586-2595 |
| Filatenkov, Alexander; Richardson, Timothy E; Daoud, Elena et al. (2017) Persistence of parenchymal and perivascular T-cells in treatment-refractory anti-N-methyl-D-aspartate receptor encephalitis. Neuroreport 28:890-895 |
