Background: Glutamate and its specific ionotropic receptors, including N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, are supposed to play an important role in neurodegeneration as well as neuronal regeneration. Although autoantibodies (aab) to glutamate receptors (GluR) have been identified in several neurologic diseases, including paraneoplastic encephalitis and Rasmussen's encephalitis (RE) with an increasing prevalence, the presence and role of anti-GluR aab in multiple sclerosis (MS) have not been studied yet. Objectives and Methods: In this study, we tested the serum samples of 56 subjects, including patients with relapsing-remitting MS (n = 25), patients with RE (n = 8), and healthy donors (HD; n = 23), for anti-GluR aab by immunoblot analysis of a panel of recombinantly expressed GluR proteins, including GluN1, GluN2C, GluA3, GluK2, and GluD2. Results: aab were mainly found directed against GluN1 and, except for one aab positive to GluK2 in 1 MS patient and 2 HD controls positive for GluA3, no other anti-GluR aab were detected. In the sera of RE patients, no anti-GluR aab were found. In patients with MS, 8 of the 25 sera (32%) tested positive for GluN1. Compared to the HD (6/23; 26%), this difference was not statistically significant (p = 0.28). Conclusions: Our study showed that if anti-GluR aab were detectable in HD and MS patients, they were mainly directed against GluN1 (in particular to oligomeric protein complexes) and were not found in RE. Those antibodies may have low titers and low affinities and might be considered an immune epiphenomenon. Hence, further studies will have to clarify their potential role as a surrogate marker for the extent of neuronal destruction or regeneration, respectively.

Keywords:
Multiple sclerosis, Rasmussen’s encephalitis, Autoimmunity, Glutamate receptors, Kainate, N-Methyl-D-aspartate, α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, B-cell response, Autoantibody
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2014
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