Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease
Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring...
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2019-09-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02253/full |
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doaj-d8a97787e33849beb9489320df1be6042020-11-24T20:50:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02253461166Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s DiseaseJonas Folke0Rasmus Rydbirk1Annemette Løkkegaard2Lisette Salvesen3Anne-Mette Hejl4Charlotte Starhof5Sára Bech6Kristian Winge7Kristian Winge8Søren Christensen9Lars Østergaard Pedersen10Susana Aznar11Bente Pakkenberg12Bente Pakkenberg13Tomasz Brudek14Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation, Hellerup, DenmarkBispebjerg Movement Disorders Biobank, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkH. Lundbeck A/S, Copenhagen, DenmarkDepartment of Immunology and Microbiology, Faculty of Health, University of Copenhagen, Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkInstitute of Clinical Medicine, Faculty of Health, University of Copenhagen, Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkAggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring autoantibodies (NAbs) with high-affinity/avidity toward α-synuclein are reduced in MSA and PD patients. Here, we aimed to evaluate the plasma immunoglobulin (Ig) composition binding α-syn and other amyloidogenic neuropathological proteins, and to correlate them with disease severity and duration in MSA and PD patients. All participants were recruited from a single neurological unit and the plasma samples were stored for later research at the Bispebjerg Movement Disorder Biobank. All patients were diagnosed according to current consensus criteria. Using multiple variable linear regression analyses, we observed higher levels of anti-α-syn IgG1 and IgG3 NAbs in MSA vs. PD, higher levels of anti-α-syn IgG2 NAbs in PD compared to controls, whereas anti-α-syn IgG4 NAbs were reduced in PD compared to MSA and controls. Anti-α-syn IgM levels were decreased in both MSA and PD. Further our data supported that MSA patients' immune system was affected with reduced IgG1 and IgM global levels compared to PD and controls, with further reduced global IgG2 levels compared to PD. These results suggest distinct autoimmune patterns in MSA and PD. These findings suggest a specific autoimmune physiological mechanism involving responses toward α-syn, differing in neurodegenerative disease with overlapping α-syn pathology.https://www.frontiersin.org/article/10.3389/fimmu.2019.02253/fullautoimmunityantigensautoantibodiesneurologyplasmaalpha-synuclein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jonas Folke Rasmus Rydbirk Annemette Løkkegaard Lisette Salvesen Anne-Mette Hejl Charlotte Starhof Sára Bech Kristian Winge Kristian Winge Søren Christensen Lars Østergaard Pedersen Susana Aznar Bente Pakkenberg Bente Pakkenberg Tomasz Brudek |
spellingShingle |
Jonas Folke Rasmus Rydbirk Annemette Løkkegaard Lisette Salvesen Anne-Mette Hejl Charlotte Starhof Sára Bech Kristian Winge Kristian Winge Søren Christensen Lars Østergaard Pedersen Susana Aznar Bente Pakkenberg Bente Pakkenberg Tomasz Brudek Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease Frontiers in Immunology autoimmunity antigens autoantibodies neurology plasma alpha-synuclein |
author_facet |
Jonas Folke Rasmus Rydbirk Annemette Løkkegaard Lisette Salvesen Anne-Mette Hejl Charlotte Starhof Sára Bech Kristian Winge Kristian Winge Søren Christensen Lars Østergaard Pedersen Susana Aznar Bente Pakkenberg Bente Pakkenberg Tomasz Brudek |
author_sort |
Jonas Folke |
title |
Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease |
title_short |
Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease |
title_full |
Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease |
title_fullStr |
Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease |
title_full_unstemmed |
Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease |
title_sort |
distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-09-01 |
description |
Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring autoantibodies (NAbs) with high-affinity/avidity toward α-synuclein are reduced in MSA and PD patients. Here, we aimed to evaluate the plasma immunoglobulin (Ig) composition binding α-syn and other amyloidogenic neuropathological proteins, and to correlate them with disease severity and duration in MSA and PD patients. All participants were recruited from a single neurological unit and the plasma samples were stored for later research at the Bispebjerg Movement Disorder Biobank. All patients were diagnosed according to current consensus criteria. Using multiple variable linear regression analyses, we observed higher levels of anti-α-syn IgG1 and IgG3 NAbs in MSA vs. PD, higher levels of anti-α-syn IgG2 NAbs in PD compared to controls, whereas anti-α-syn IgG4 NAbs were reduced in PD compared to MSA and controls. Anti-α-syn IgM levels were decreased in both MSA and PD. Further our data supported that MSA patients' immune system was affected with reduced IgG1 and IgM global levels compared to PD and controls, with further reduced global IgG2 levels compared to PD. These results suggest distinct autoimmune patterns in MSA and PD. These findings suggest a specific autoimmune physiological mechanism involving responses toward α-syn, differing in neurodegenerative disease with overlapping α-syn pathology. |
topic |
autoimmunity antigens autoantibodies neurology plasma alpha-synuclein |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02253/full |
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