No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors,Translational Neurodegeneration

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No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors
Translational Neurodegeneration ( IF 10.8 ) Pub Date : 2019-04-03 , DOI: 10.1186/s40035-019-0153-0
Franziska Hopfner _{1,

2} , Stefanie H Müller ₁ , Dagmar Steppat ₃ , Joanna Miller ₃ , Nele Schmidt ₁ , Klaus-Peter Wandinger ₄ , Frank Leypoldt _{1,

4} , Daniela Berg _{1,

5,

6} , Andre Franke ₇ , Wolfgang Lieb ₈ , Lukas Tittmann ₈ , Monika Balzer-Geldsetzer _{9,

10} , Simon Baudrexel _{11,

12} , Richard Dodel _{9,

10} , Ruediger Hilker-Roggendorf _{11,

12} , Elke Kalbe _{13,

14} , Jan Kassubek ₁₅ , Thomas Klockgether ₁₆ , Inga Liepelt-Scarfone _{5,

6} , Brit Mollenhauer _{17,

18} , Petra Neuser ₁₉ , Kathrin Reetz _{20,

21} , Oliver Riedel ₂₂ , Claudia Schulte _{5,

6} , Jörg B Schulz _{20,

21} , Annika Spottke ₁₆ , Alexander Storch _{23,

24,

25} , Claudia Trenkwalder _{17,

18} , Hans-Ulrich Wittchen _{2,

26,

27} , Karsten Witt _{1,

28,

29} , Ullrich Wüllner ₁₆ , Günther Deuschl ₁ , Gregor Kuhlenbäumer ₁

Affiliation

1Department of Neurology, University Hospital Schleswig Holstein, Arnold-Heller Str. 3, 24105 Kiel, Germany.
27Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstraße 7, 80336 München, Germany.
2Center of Blood Transfusion, University Hospital Schleswig Holstein, Kiel & Lübeck, Germany.
3Department of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany.
14Center for Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany.
15DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
4Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.
5Institute of Epidemiology, University Hospital Schleswig-Holstein, Kiel, Germany.
6Chair of Geriatric Medicine, University Hospital Essen, Essen, Germany.
7Department of Neurology, Philipps-University Marburg, Marburg, Germany.
8Department of Neurology, Goethe University, Frankfurt/Main, Germany.
9Brain Imaging Center, Goethe University, Frankfurt/Main, Germany.
10Department of Medical Psychology | Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Cologne, Cologne, Germany.
11Psychological Gerontology, Institute of Gerontology, University of Vechta, Vechta, Germany.
12Department of Neurology, University of Ulm, Ulm, Germany.
13Department of Neurology, University of Bonn, and German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
16Paracelsus-Elena-Klinik, Kassel, Germany.
17Institute of Neuropathology and Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
18Coordinating Centre for Clinical Trials, Philipps-University, Marburg, Germany.
19Department of Neurology, RWTH Aachen University, Aachen, Germany.
20JARA-BRAIN Institute of Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Aachen, Germany.
21Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstrasse 30, 28359 Bremen, Germany.
22Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
23German Center for Neurodegenerative Diseases (DZNE), Research Site Rostock, 18147 Rostock, Germany.
24Department of Neurology, University of Rostock, 18147 Rostock, Germany.
25Technische Universtität Dresden, Institute of Clinical Psychology and Psychotherapy, Chemnitzer Str. 46, 01187 Dresden, Germany.
26Technische Universtität Dresden, Center for Epidemiological and Longitudinal Studies (CELOS), Chemnitzer Str. 46, 01187 Dresden, Germany.
28Department of Neurology, European Medical School, University Oldenburg, Oldenburg, Germany.
29Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.

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. 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. 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. 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.

中文翻译：

帕金森病与针对 NMDA 型谷氨酸受体的自身抗体之间没有关联

针对 N-甲基-D-天冬氨酸 (NMDA) 型谷氨酸受体的 IgG 类自身抗体定义了一种新的自身免疫性脑炎实体。检查 NMDA IgA/IgM 抗体在帕金森病伴/不伴痴呆患者中的流行率的研究产生了相互矛盾的结果。我们在没有和有认知障碍的帕金森患者（n = 296）和没有神经精神疾病的对照（n = 295）的大型、良好表型样本中测量了 NMDA 抗体。详细的表型分析和大量数据使抗体状态与诊断亚组以及疾病严重程度和认知障碍的定量指标具有统计学意义的相关性。使用完善的验证试验分析患者和对照血清中的 NMDA 抗体。我们使用抗 NMDA 抗体阳性作为主要的自变量，并将其与疾病状态和表型特征相关联。NMDA IgA/IgM 抗体的频率在帕金森患者 (13%) 中低于对照组 (22%)，在两组中均高于之前的研究。根据认知障碍，NMDA IgA/IgM 抗体与帕金森病的诊断亚类既不显着相关，也不与疾病严重程度和认知障碍的定量指标显着相关。阳性 NMDA 抗体状态与对照组的年龄呈正相关，但与帕金森患者无关。NMDA 抗体不太可能在帕金森病的发病机制或进展中发挥重要作用，例如帕金森病伴痴呆，

更新日期：2020-04-22

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