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IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment

Item Type:Article
Title:IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment
Creators Name:Pruess, H. and Hoeltje, M. and Maier, N. and Gomez, A. and Buchert, R. and Harms, L. and Ahnert-Hilger, G. and Schmitz, D. and Terborg, C. and Kopp, U. and Klingbeil, C. and Probst, C. and Kohler, S. and Schwab, J.M. and Stoecker, W. and Dalmau, J. and Wandinger, K.P.
Abstract:Objective: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. Methods: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. Results: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. Conclusions: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.
Keywords:Adrenal Cortex Hormones, Alzheimer Disease, Atrophy, Autoimmunity, Biological Markers, Cognition Disorders, Cyclophosphamide, Disease Progression, Electrophysiology, Fluorodeoxyglucose F18, Frontal Lobe, Hippocampus, Immunoglobulin A, Immunohistochemistry, Immunotherapy, Lewy Body Disease, Magnetic Resonance Imaging, Murine-Derived Monoclonal Antibodies, Neurons, N-Methyl-D-Aspartate Receptors, Plasma Exchange, Positron-Emission Tomography, Radiopharmaceuticals, Synapses, Temporal Lobe, Treatment Outcome, Western Blotting
Publisher:American Academy of Neurology
Page Range:1743-1753
Date:29 May 2012
Official Publication:https://doi.org/10.1212/WNL.0b013e318258300d
PubMed:View item in PubMed

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