PMID- 28592329
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20181113
IS  - 1750-1326 (Electronic)
IS  - 1750-1326 (Linking)
VI  - 12
IP  - 1
DP  - 2017 Jun 7
TI  - Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a 
      step towards immunotherapeutic strategies.
PG  - 44
LID - 10.1186/s13024-017-0187-7 [doi]
LID - 44
AB  - BACKGROUND: Parkinson's' disease (PD) and Multiple System Atrophy (MSA) are 
      progressive brain disorders characterized by intracellular accumulations of 
      alpha-synuclein and nerve cell loss in specific brain areas. This loss causes 
      problems with movement, balance and/or autonomic functions. Naturally occurring 
      autoantibodies (NAbs) play potentially an important role in clearing or/and 
      blocking circulating pathological proteins. Little is known about the functional 
      properties of anti-alpha-synuclein NAbs in PD and MSA, and there have been opposing 
      reports regarding their plasma concentrations in these disorders. METHODS: We 
      have investigated the apparent affinity of anti-alpha-synuclein NAbs in plasma 
      samples from 46 PD patients, 18 MSA patients and 41 controls using competitive 
      enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) set-ups. 
      RESULTS: We found that the occurrence of high affinity anti-alpha-synuclein NAbs in 
      plasma from PD patients is reduced compared to healthy controls, and nearly 
      absent in plasma from MSA patients. Also, levels of alpha-synuclein/NAbs 
      immunocomplexes is substantially reduced in plasma from both patient groups. 
      Further, cross binding of anti-alpha-synuclein NAbs with beta- and gamma-synuclein monomers 
      suggest, the high affinity anti-alpha-synuclein plasma component, seen in healthy 
      individuals, is directed mainly against C-terminal epitopes. Furthermore, we also 
      observed reduced occurrence of high affinity anti-phosphorylated-alpha-synuclein NAbs 
      in plasma from PD and MSA patients. CONCLUSIONS: One interpretation implies that 
      these patients may have impaired ability to clear and/or block the effects of 
      pathological alpha-synuclein due to insufficient/absent concentration of NAbs and as 
      such provides a rationale for testing immune-based therapeutic strategies 
      directed against pathological alpha-synuclein. Following this interpretation, we can 
      hypothesize that high affinity autoantibodies efficiently bind and clear 
      potentially pathological species of alpha-synuclein in healthy brain, and that this 
      mechanism is impaired or absent in PD and MSA patients.
FAU - Brudek, Tomasz
AU  - Brudek T
AUID- ORCID: 0000-0001-5453-1817
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, 
      DK-2400, Copenhagen N, Denmark. tomasz.brudek@regionh.dk.
AD  - Bispebjerg Movement Disorders Biobank, Bispebjerg-Frederiksberg Hospital, 
      Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, DK-2400, 
      Copenhagen N, Denmark. tomasz.brudek@regionh.dk.
FAU - Winge, Kristian
AU  - Winge K
AD  - Department of Neurology, Bispebjerg-Frederiksberg Hospital, Copenhagen University 
      Hospital, Bispebjerg, Bispebjerg Bakke 23, DK-2400, Copenhagen N, Denmark.
AD  - Bispebjerg Movement Disorders Biobank, Bispebjerg-Frederiksberg Hospital, 
      Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, DK-2400, 
      Copenhagen N, Denmark.
FAU - Folke, Jonas
AU  - Folke J
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, 
      DK-2400, Copenhagen N, Denmark.
FAU - Christensen, Soren
AU  - Christensen S
AD  - , H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Copenhagen, Denmark.
FAU - Fog, Karina
AU  - Fog K
AD  - , H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Copenhagen, Denmark.
FAU - Pakkenberg, Bente
AU  - Pakkenberg B
AD  - Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg 
      Hospital, Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, 
      DK-2400, Copenhagen N, Denmark.
AD  - Institute of Clinical Medicine, Faculty of Health, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Pedersen, Lars Ostergaard
AU  - Pedersen LO
AD  - , H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20170607
PL  - England
TA  - Mol Neurodegener
JT  - Molecular neurodegeneration
JID - 101266600
RN  - 0 (Autoantibodies)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Aged
MH  - Autoantibodies/*immunology
MH  - Brain/metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple System Atrophy/*immunology/pathology
MH  - Parkinson Disease/diagnosis/*immunology
MH  - alpha-Synuclein/metabolism
PMC - PMC5463400
OTO - NOTNLM
OT  - Alpha-synuclein
OT  - Autoantibodies, Plasma
OT  - Multiple System Atrophy
OT  - Parkinson's disease
OT  - Synuclein
EDAT- 2017/06/09 06:00
MHDA- 2018/04/18 06:00
PMCR- 2017/06/07
CRDT- 2017/06/09 06:00
PHST- 2016/12/20 00:00 [received]
PHST- 2017/06/02 00:00 [accepted]
PHST- 2017/06/09 06:00 [entrez]
PHST- 2017/06/09 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/06/07 00:00 [pmc-release]
AID - 10.1186/s13024-017-0187-7 [pii]
AID - 187 [pii]
AID - 10.1186/s13024-017-0187-7 [doi]
PST - epublish
SO  - Mol Neurodegener. 2017 Jun 7;12(1):44. doi: 10.1186/s13024-017-0187-7.