PMID- 34020303
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20220126
IS  - 1873-5126 (Electronic)
IS  - 1353-8020 (Linking)
VI  - 87
DP  - 2021 Jun
TI  - Cerebrospinal fluid and plasma distribution of anti-alpha-synuclein IgMs and IgGs in 
      multiple system atrophy and Parkinson's disease.
PG  - 98-104
LID - S1353-8020(21)00164-4 [pii]
LID - 10.1016/j.parkreldis.2021.05.001 [doi]
AB  - INTRODUCTION: Ubiquitous naturally occurring autoantibodies (nAbs) against 
      alpha-synuclein (alpha-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-alpha-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-alpha-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-alpha-syn IgG nAbs were reduced in CSF samples from MSA 
      and PD patients compared to controls. Furthermore, anti-alpha-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-alpha-syn IgG subclasses presented 
      disease-specific profiles both in CSF and plasma. Anti-alpha-syn IgG1, IgG2 and IgG3 
      levels were relatively increased in CSF of MSA patients, whereas PD patients 
      showed increased anti-alpha-syn IgG2 and reduced anti-alpha-syn IgG4 levels. CONCLUSIONS: 
      Differences in the plasma/CSF distribution of anti-alpha-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 alpha-syn. The 
      differing alpha-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.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Folke, Jonas
AU  - Folke J
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, University Hospital of Copenhagen, Nielsine Nielsens Vej 6B, entrance 
      11B, DK-2400, Copenhagen, NW, Denmark; Copenhagen Center for Translational 
      Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, 
      Nielsine Nielsens Vej, 4B, entrance 80, DK-2400, Copenhagen, NW, Denmark. 
      Electronic address: Jonas.folke@regionh.dk.
FAU - Rydbirk, Rasmus
AU  - Rydbirk R
AD  - Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 
      5, DK-2200, Copenhagen, N, Denmark.
FAU - Lokkegaard, Annemette
AU  - Lokkegaard A
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital 
      of Copenhagen, Ebba Lunds Vej 44, DK-2400, Copenhagen, NW, Denmark.
FAU - Hejl, Anne-Mette
AU  - Hejl AM
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital 
      of Copenhagen, Ebba Lunds Vej 44, DK-2400, Copenhagen, NW, Denmark.
FAU - Winge, Kristian
AU  - Winge K
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital 
      of Copenhagen, Ebba Lunds Vej 44, DK-2400, Copenhagen, NW, Denmark; Novo Nordisk 
      Foundation, Tuborg Havnevej 19, DK-2900, Hellerup, Denmark.
FAU - Starhof, Charlotte
AU  - Starhof C
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital 
      of Copenhagen, Ebba Lunds Vej 44, DK-2400, Copenhagen, NW, Denmark.
FAU - Salvesen, Lisette
AU  - Salvesen L
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, University Hospital 
      of Copenhagen, Ebba Lunds Vej 44, DK-2400, Copenhagen, NW, Denmark.
FAU - Pedersen, Lars Ostergaard
AU  - Pedersen LO
AD  - H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
FAU - Aznar, Susana
AU  - Aznar S
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, University Hospital of Copenhagen, Nielsine Nielsens Vej 6B, entrance 
      11B, DK-2400, Copenhagen, NW, Denmark; Copenhagen Center for Translational 
      Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, 
      Nielsine Nielsens Vej, 4B, entrance 80, DK-2400, Copenhagen, NW, Denmark.
FAU - Pakkenberg, Bente
AU  - Pakkenberg B
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, University Hospital of Copenhagen, Nielsine Nielsens Vej 6B, entrance 
      11B, DK-2400, Copenhagen, NW, Denmark; Institute of Clinical Medicine, Faculty of 
      Health, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, N, 
      Denmark.
FAU - Brudek, Tomasz
AU  - Brudek T
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, University Hospital of Copenhagen, Nielsine Nielsens Vej 6B, entrance 
      11B, DK-2400, Copenhagen, NW, Denmark; Copenhagen Center for Translational 
      Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, 
      Nielsine Nielsens Vej, 4B, entrance 80, DK-2400, Copenhagen, NW, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210512
PL  - England
TA  - Parkinsonism Relat Disord
JT  - Parkinsonism & related disorders
JID - 9513583
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Autoantibodies)
RN  - 0 (Biomarkers)
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
RN  - 0 (anti-IgG)
RN  - 0 (anti-IgM)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Anti-Idiotypic/blood/cerebrospinal fluid/immunology
MH  - *Autoantibodies/blood/cerebrospinal fluid/immunology
MH  - Biomarkers/blood/cerebrospinal fluid
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Multiple System Atrophy/blood/cerebrospinal fluid/immunology
MH  - *Parkinson Disease/blood/cerebrospinal fluid/immunology
MH  - alpha-Synuclein/*immunology
OTO - NOTNLM
OT  - Alpha-synuclein
OT  - Autoantibodies
OT  - Biomarker
OT  - Cerebrospinal fluids
OT  - Multiple system atrophy
OT  - Parkinson's disease
EDAT- 2021/05/22 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/05/21 20:27
PHST- 2020/11/24 00:00 [received]
PHST- 2021/04/09 00:00 [revised]
PHST- 2021/05/03 00:00 [accepted]
PHST- 2021/05/22 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/05/21 20:27 [entrez]
AID - S1353-8020(21)00164-4 [pii]
AID - 10.1016/j.parkreldis.2021.05.001 [doi]
PST - ppublish
SO  - Parkinsonism Relat Disord. 2021 Jun;87:98-104. doi: 
      10.1016/j.parkreldis.2021.05.001. Epub 2021 May 12.