Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease

Jonas Folke; Rasmus Rydbirk; Annemette Løkkegaard; Lisette Salvesen; Anne Mette Hejl; Charlotte Starhof; Sára Bech; Kristian Winge; Søren Christensen; Lars Østergaard Pedersen; Susana Aznar; Bente Pakkenberg; Tomasz Brudek

doi:10.3389/fimmu.2019.02253

Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease

Jonas Folke, Rasmus Rydbirk, Annemette Løkkegaard, Lisette Salvesen, Anne Mette Hejl, Charlotte Starhof, Sára Bech, Kristian Winge, Søren Christensen, Lars Østergaard Pedersen, Susana Aznar, Bente Pakkenberg, Tomasz Brudek^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

6 Citationer (Scopus)

8 Downloads (Pure)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	2253
Tidsskrift	Frontiers in Immunology
Vol/bind	10
Udgave nummer	SEP
ISSN	1664-3224
DOI	https://doi.org/10.3389/fimmu.2019.02253
Status	Udgivet - 2019

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10.3389/fimmu.2019.02253Licens: CC BY

Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s DiseaseForlagets udgivne version, 759 KBLicens: CC BY

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Folke, J., Rydbirk, R., Løkkegaard, A., Salvesen, L., Hejl, A. M., Starhof, C., Bech, S., Winge, K., Christensen, S., Pedersen, L. Ø., Aznar, S., Pakkenberg, B., & Brudek, T. (2019). Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease. Frontiers in Immunology, 10(SEP), Artikel 2253. https://doi.org/10.3389/fimmu.2019.02253

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title = "Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson{\textquoteright}s disease",

abstract = "Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson{\textquoteright}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{\textquoteright} 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.",

keywords = "Alpha-synuclein, Antigens, Autoantibodies, Autoimmunity, Multiple system atrophy, Neurology, Parkinson{\textquoteright}s disease, Plasma",

author = "Jonas Folke and Rasmus Rydbirk and Annemette L{\o}kkegaard and Lisette Salvesen and Hejl, {Anne Mette} and Charlotte Starhof and S{\'a}ra Bech and Kristian Winge and S{\o}ren Christensen and Pedersen, {Lars {\O}stergaard} and Susana Aznar and Bente Pakkenberg and Tomasz Brudek",

year = "2019",

doi = "10.3389/fimmu.2019.02253",

language = "English",

volume = "10",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Research Foundation",

number = "SEP",

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TY - JOUR

T1 - Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease

AU - Folke, Jonas

AU - Rydbirk, Rasmus

AU - Løkkegaard, Annemette

AU - Salvesen, Lisette

AU - Hejl, Anne Mette

AU - Starhof, Charlotte

AU - Bech, Sára

AU - Winge, Kristian

AU - Christensen, Søren

AU - Pedersen, Lars Østergaard

AU - Aznar, Susana

AU - Pakkenberg, Bente

AU - Brudek, Tomasz

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Alpha-synuclein

KW - Antigens

KW - Autoantibodies

KW - Autoimmunity

KW - Multiple system atrophy

KW - Neurology

KW - Parkinson’s disease

KW - Plasma

U2 - 10.3389/fimmu.2019.02253

DO - 10.3389/fimmu.2019.02253

M3 - Journal article

C2 - 31616427

AN - SCOPUS:85073149996

SN - 1664-3224

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

IS - SEP

M1 - 2253

ER -

Distinct autoimmune anti-α-synuclein antibody patterns in multiple system atrophy and parkinson’s disease

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