No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors.

Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment ( n  = 296) and controls ( n  = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.
Methods: NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.
Results: The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.
Conclusion: It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.
Competing Interests: Ethics committee approval was obtained for all studies involved (Dept. of Neurology of Kiel University, Landscape, popgen).Nothing to report.F. Hopfner received grants from the German Research Council (DFG), Stefanie H. Müller, Dagmar Steppat, Joanna Miller, Nele Schmidt, Claudia Schulte, Petra Neuser, Inga Liepelt-Scarfone, Brit Mollenhauer, Lucas Tittmann, Monika Balzer-Geldsetzer, Simon Baudrexel, Elke Kalbe, Oliver Riedel report no disclosures. Richard Dodel has received lecture fees from Novartis, Lilly, Octapharma, Pfizer and has received research support from the EU Horizon 2020, the AOK Gesundheitskasse Hessen, AOK Gesundheitskasse Sachsen und Thüringen, the M.J.Fox Foundation, the Internationale Parkinson Fonds and the Faber-Stiftung. Frank Leypoldt, Klaus-Peter Wandinger Andre Franke received grants from the German Research Council (DFG). Wolfgang Lieb was supported by a grant from the German Federal Ministry of Education and Research (01EY1103). Daniela Berg is a member of the UCB advisory board and receives grants from Michael J. Fox Foundation, Janssen Pharmaceutica N.V., German Parkinson’s Disease Association (dPV), BMWi, BMBF, Parkinson Fonds Deutschland gGmbH, UCB Pharma GmbH, TEVA Pharma GmbH, EU, Novartis Pharma GmbH, Lundbeck, and Damp foundation. Ruediger Hilker-Roggendorf has received speaker honoraria from Medtronic, Orion, GlaxoSmithKline, TEVA, Cephalon, Solvay, Desitin, Ipsen, Merz, Archimedes Pharma and Boehringer Ingelheim as well as travel funding from Medtronic, Allergan and Cephalon. He has served on a scientific advisory board for Cephalon and has received research funding from the Deutsche Parkinson Vereinigung (dPV), Bundesministerium für Bildung und Forschung and Goethe University Frankfurt. Alexander Storch has received funding from the Deutsche Forschungsgemeinschaft (German Research Association) and the Helmholtz-Association. He has received honoraria for presentations/advisory boards/consultations from AbbVie, Bial, Bayer, Grünenthal, Teva, Desitin and UCB. He has received royalties from Kohlhammer Verlag and Elsevier Press. He serves as an editorial board member of Stem Cells, Stem Cells International, Open Biotechnology Journals, and jbc The Journal of Biological Chemistry. Annika Spottke, Jörg B. Schulz, Karsten Witt and Hans-Ulrich Wittchen report no disclosures. Jan Kassubek has received consulting fees as an advisory board member and honoraria as a speaker from UCB Pharma, Bial, Teva Pharmaceuticals, AbbVie, Zambon, Medtronic, Novartis, Desitin, Boehringer Ingelheim. Thomas Klockgether receives/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Bundesministerium für Gesundheit (BMG), the Robert Bosch Foundation. the European Union (EU), and the National Institutes of Health (NIH). He serves on the editorial board of The Cerebellum and the Journal of Neurology. He has received consulting fees from Biohaven. Ullrich Wüllner served as consultant and lecturer and on advisory boards for Boehringer-Ingelheim, Glaxo-SmithKline, Pfizer Pharma GmbH, UCB Pharma and received grant/research funding from BMBF, DFG, NAF, dPV and the EU (6th framework). Claudia Trenkwalder reports personal fees from Britannia, during the conduct of the study; grants from Michael J. Fox Foundation, the European Commission Horizon 2020 Program: ‘Propag-Ageing’, MundiPharma, Vifor, personal fees from Britannia, Novartis, UCB, MundiPharma, Vifor, Benevolent, Orion Pharma, Pfizer, personal fees from Grünenthal, UCB and AbbVie., outside the submitted work. Kathrin Reetz is funded by the German Federal Ministry of Education and Research (BMBF 01GQ1402), has received honoraria for presentations from Lilly and research grants from Pfizer, Merck and the Alzheimer Forschung Initiative e.V. (AFI 13812). Günther Deuschl has received lecture fees from UCB, Medtronic and Desitin and has been serving as a consultant for Medtronic, Sapiens, Boston Scientific and Britannica. He received royalties from Thieme publishers. He receives through his institution funding for his research from the German Research Council, the German Ministery of Education and Health and Medtronic. All authors are government employees. Gregor Kuhlenbäumer receives research support from the German Research Council (DFG) and the Christian-Albrechts-University Kiel.