Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease
Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Jonas Folke Emil Bergholt Bente Pakkenberg Susana Aznar Tomasz Brudek |
| author_facet | Jonas Folke Emil Bergholt Bente Pakkenberg Susana Aznar Tomasz Brudek |
| author_sort | Jonas Folke |
| collection | DOAJ |
| description | Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-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 αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-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-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, 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. |
| first_indexed | 2024-03-09T23:35:19Z |
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| id | doaj.art-a3ed666ed1634a79b0d98aef2c916dba |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:35:19Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3ed666ed1634a79b0d98aef2c916dba2023-11-23T17:02:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312655410.3390/ijms23126554Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s DiseaseJonas Folke0Emil Bergholt1Bente Pakkenberg2Susana Aznar3Tomasz Brudek4Centre for Neuroscience & Stereology, Department of Neurology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, DenmarkCentre for Neuroscience & Stereology, Department of Neurology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, DenmarkCentre for Neuroscience & Stereology, Department of Neurology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, DenmarkCentre for Neuroscience & Stereology, Department of Neurology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, DenmarkCentre for Neuroscience & Stereology, Department of Neurology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, DK-2400 Copenhagen NV, DenmarkMultiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-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 αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-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-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, 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.https://www.mdpi.com/1422-0067/23/12/6554multiple system atrophyParkinson’s diseasenaturally occurring autoantibodies (nAbs)alpha-synucleinprodromal |
| spellingShingle | Jonas Folke Emil Bergholt Bente Pakkenberg Susana Aznar Tomasz Brudek Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease International Journal of Molecular Sciences multiple system atrophy Parkinson’s disease naturally occurring autoantibodies (nAbs) alpha-synuclein prodromal |
| title | Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease |
| title_full | Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease |
| title_fullStr | Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease |
| title_full_unstemmed | Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease |
| title_short | Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease |
| title_sort | alpha synuclein autoimmune decline in prodromal multiple system atrophy and parkinson s disease |
| topic | multiple system atrophy Parkinson’s disease naturally occurring autoantibodies (nAbs) alpha-synuclein prodromal |
| url | https://www.mdpi.com/1422-0067/23/12/6554 |
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