PMID- 35742998
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20240514
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 12
DP  - 2022 Jun 12
TI  - Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and 
      Parkinson's Disease.
LID - 10.3390/ijms23126554 [doi]
LID - 6554
AB  - Multiple-system trophy (MSA) and Parkinson's Disease (PD) are both progressive, 
      neurodegenerative diseases characterized by neuropathological deposition of 
      aggregated alpha-synuclein (alphaSyn). The causes behind this aggregation are still 
      unknown. We have reported aberrancies in MSA and PD patients in naturally 
      occurring autoantibodies (nAbs) against alphaSyn (anti-alphaSyn-nAbs), which are 
      important partakers in anti-aggregatory processes, immune-mediated clearance, and 
      anti-inflammatory functions. To elaborate further on the timeline of autoimmune 
      aberrancies towards alphaSyn, we investigated here the Immunoglobulin (Ig) affinity 
      profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-alphaSyn-nAbs in 
      serum samples from prodromal (p) phases of MSA and PD. Using an 
      electrochemiluminescence competition immunoassay, we confirmed that the 
      repertoire of high-affinity anti-alphaSyn-nAbs is significantly reduced in pMSA and 
      pPD. Further, we demonstrated that pPD had increased anti-alphaSyn IgG-total levels 
      compared to pMSA and controls, concordant with increased anti-alphaSyn IgG1 levels in 
      pPD. Anti-alphaSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with 
      controls, whereas anti-alphaSyn IgG3 levels were reduced in pMSA compared to pPD and 
      controls. The results indicate that the impaired reactivity towards alphaSyn occurs 
      prior to disease onset. The apparent lack of high-affinity anti-alphaSyn nAbs may 
      result in reduced clearance of alphaSyn, leading to aggregation of the protein. Thus, 
      this study provides novel insights into possible causes behind the pathogenesis 
      in synucleinopathies such as MSA and PD.
FAU - Folke, Jonas
AU  - Folke J
AUID- ORCID: 0000-0002-0940-3098
AD  - Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen 
      University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, 
      Denmark.
AD  - Copenhagen Center for Translational Research, Copenhagen University Hospital, 
      Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, Denmark.
FAU - Bergholt, Emil
AU  - Bergholt E
AD  - Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen 
      University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, 
      Denmark.
FAU - Pakkenberg, Bente
AU  - Pakkenberg B
AD  - Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen 
      University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, 
      Denmark.
AD  - Institute of Clinical Medicine, Faculty of Health, University of Copenhagen, 
      DK-2100 Copenhagen O, Denmark.
FAU - Aznar, Susana
AU  - Aznar S
AD  - Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen 
      University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, 
      Denmark.
AD  - Copenhagen Center for Translational Research, Copenhagen University Hospital, 
      Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, Denmark.
FAU - Brudek, Tomasz
AU  - Brudek T
AD  - Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen 
      University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, 
      Denmark.
AD  - Copenhagen Center for Translational Research, Copenhagen University Hospital, 
      Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, Denmark.
LA  - eng
GR  - TPP 10-008/HX/HSRD VA/United States
PT  - Journal Article
DEP - 20220612
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Autoantibodies
MH  - Humans
MH  - Immunoglobulin G
MH  - *Multiple System Atrophy
MH  - *Parkinson Disease/metabolism
MH  - alpha-Synuclein/metabolism
PMC - PMC9224313
OTO - NOTNLM
OT  - Parkinson's disease
OT  - alpha-synuclein
OT  - multiple system atrophy
OT  - naturally occurring autoantibodies (nAbs)
OT  - prodromal
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/06/12
CRDT- 2022/06/24 01:21
PHST- 2022/05/24 00:00 [received]
PHST- 2022/06/08 00:00 [revised]
PHST- 2022/06/10 00:00 [accepted]
PHST- 2022/06/24 01:21 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/06/12 00:00 [pmc-release]
AID - ijms23126554 [pii]
AID - ijms-23-06554 [pii]
AID - 10.3390/ijms23126554 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jun 12;23(12):6554. doi: 10.3390/ijms23126554.