Cerebrospinal fluid and plasma distribution of anti-α-synuclein IgMs and IgGs in multiple system atrophy and Parkinson's disease
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Cerebrospinal fluid and plasma distribution of anti-α-synuclein IgMs and IgGs in multiple system atrophy and Parkinson's disease. / Folke, Jonas; Rydbirk, Rasmus; Løkkegaard, Annemette; Hejl, Anne Mette; Winge, Kristian; Starhof, Charlotte; Salvesen, Lisette; Pedersen, Lars Østergaard; Aznar, Susana; Pakkenberg, Bente; Brudek, Tomasz.
In: Parkinsonism and Related Disorders, Vol. 87, 2021, p. 98-104.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Cerebrospinal fluid and plasma distribution of anti-α-synuclein IgMs and IgGs in multiple system atrophy and Parkinson's disease
AU - Folke, Jonas
AU - Rydbirk, Rasmus
AU - Løkkegaard, Annemette
AU - Hejl, Anne Mette
AU - Winge, Kristian
AU - Starhof, Charlotte
AU - Salvesen, Lisette
AU - Pedersen, Lars Østergaard
AU - Aznar, Susana
AU - Pakkenberg, Bente
AU - Brudek, Tomasz
N1 - Publisher Copyright: © 2021 Elsevier Ltd
PY - 2021
Y1 - 2021
N2 - Introduction: Ubiquitous naturally occurring autoantibodies (nAbs) against alpha-synuclein (α-syn) may play important roles in the pathogenesis of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Recently, we reported reduced high-affinity/avidity anti-α-syn nAbs levels in plasma from MSA and PD patients, along with distinct inter-group immunoglobulin (Ig)G subclass distributions. The extent to which these observations in plasma may reflect corresponding levels in the cerebrospinal fluid (CSF) is unknown. Methods: Using competitive and indirect ELISAs, we investigated the affinity/avidity of CSF anti-α-syn nAbs as well as the CSF and plasma distribution of IgG subclasses and IgM nAbs in a cross-sectional cohort of MSA and PD patients. Results: Repertoires of high-affinity/avidity anti-α-syn IgG nAbs were reduced in CSF samples from MSA and PD patients compared to controls. Furthermore, anti-α-syn IgM nAb levels were relatively lower in CSF and plasma from MSA patients but were reduced only in plasma from PD patients. Interestingly, anti-α-syn IgG subclasses presented disease-specific profiles both in CSF and plasma. Anti-α-syn IgG1, IgG2 and IgG3 levels were relatively increased in CSF of MSA patients, whereas PD patients showed increased anti-α-syn IgG2 and reduced anti-α-syn IgG4 levels. Conclusions: Differences in the plasma/CSF distribution of anti-α-syn nAbs seem to be a common feature of synucleinopathies. Our data add further support to the notion that MSA and PD patients may have compromised immune reactivity towards α-syn. The differing α-syn-specific systemic immunological responses may reflect their specific disease pathophysiologies. These results are encouraging for further investigation of these immunological mechanisms in neurodegenerative diseases.
AB - Introduction: Ubiquitous naturally occurring autoantibodies (nAbs) against alpha-synuclein (α-syn) may play important roles in the pathogenesis of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Recently, we reported reduced high-affinity/avidity anti-α-syn nAbs levels in plasma from MSA and PD patients, along with distinct inter-group immunoglobulin (Ig)G subclass distributions. The extent to which these observations in plasma may reflect corresponding levels in the cerebrospinal fluid (CSF) is unknown. Methods: Using competitive and indirect ELISAs, we investigated the affinity/avidity of CSF anti-α-syn nAbs as well as the CSF and plasma distribution of IgG subclasses and IgM nAbs in a cross-sectional cohort of MSA and PD patients. Results: Repertoires of high-affinity/avidity anti-α-syn IgG nAbs were reduced in CSF samples from MSA and PD patients compared to controls. Furthermore, anti-α-syn IgM nAb levels were relatively lower in CSF and plasma from MSA patients but were reduced only in plasma from PD patients. Interestingly, anti-α-syn IgG subclasses presented disease-specific profiles both in CSF and plasma. Anti-α-syn IgG1, IgG2 and IgG3 levels were relatively increased in CSF of MSA patients, whereas PD patients showed increased anti-α-syn IgG2 and reduced anti-α-syn IgG4 levels. Conclusions: Differences in the plasma/CSF distribution of anti-α-syn nAbs seem to be a common feature of synucleinopathies. Our data add further support to the notion that MSA and PD patients may have compromised immune reactivity towards α-syn. The differing α-syn-specific systemic immunological responses may reflect their specific disease pathophysiologies. These results are encouraging for further investigation of these immunological mechanisms in neurodegenerative diseases.
KW - Alpha-synuclein
KW - Autoantibodies
KW - Biomarker
KW - Cerebrospinal fluids
KW - Multiple system atrophy
KW - Parkinson's disease
U2 - 10.1016/j.parkreldis.2021.05.001
DO - 10.1016/j.parkreldis.2021.05.001
M3 - Journal article
C2 - 34020303
AN - SCOPUS:85106527926
VL - 87
SP - 98
EP - 104
JO - Parkinsonism & Related Disorders
JF - Parkinsonism & Related Disorders
SN - 1353-8020
ER -
ID: 272174955