The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease
The accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson’s disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Sy...
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2218-273X/13/9/1303 |
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| author | Alexandra Albus Yannick Kronimus Monika Burg-Roderfeld Hendrik van der Wurp Dieter Willbold Tamar Ziehm Richard Dodel Jean Alexander Ross |
| author_facet | Alexandra Albus Yannick Kronimus Monika Burg-Roderfeld Hendrik van der Wurp Dieter Willbold Tamar Ziehm Richard Dodel Jean Alexander Ross |
| author_sort | Alexandra Albus |
| collection | DOAJ |
| description | The accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson’s disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Syn. This potentially demonstrates an already existing, naturally decomposing, and protective system. Thus, quantitative or qualitative alterations, such as the modified antigen binding of so-called naturally occurring autoantibodies against α-Syn (nAbs-α-Syn), may induce disease onset and/or progression. We investigated the serum titers and binding characteristics of nAbs-α-Syn in patients suffering from sporadic Parkinson’s disease (n = 38), LRRK2 mutation carriers (n = 25), and healthy controls (n = 22). Methods: Titers of nAbs-α-Syn were assessed with ELISA and binding affinities and kinetics with SPR. Within the patient cohort, we discriminated between idiopathic and genetic (LRRK2-mutated) variants. Results: ELISA experiments revealed no significant differences in nAbs-α-Syn serum titers among the three cohorts. Moreover, the α-Syn avidity of nAbs-α-Syn was also unchanged. Conclusions: Our findings indicate that nAbs-α-Syn concentrations or affinities in healthy and diseased persons do not differ, independent of mutations in LRRK2. |
| first_indexed | 2024-03-10T22:59:27Z |
| format | Article |
| id | doaj.art-84da892dc7cc4d129de8969df7963d3a |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T22:59:27Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-84da892dc7cc4d129de8969df7963d3a2023-11-19T09:45:06ZengMDPI AGBiomolecules2218-273X2023-08-01139130310.3390/biom13091303The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s DiseaseAlexandra Albus0Yannick Kronimus1Monika Burg-Roderfeld2Hendrik van der Wurp3Dieter Willbold4Tamar Ziehm5Richard Dodel6Jean Alexander Ross7Therapy Research in Neurogeriatrics, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, GermanyTherapy Research in Neurogeriatrics, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, GermanyDepartment of Chemistry and Biology, Fresenius University of Applied Sciences, 65510 Idstein, GermanyTherapy Research in Neurogeriatrics, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, GermanyInstitute of Physical Biology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Physical Biology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyTherapy Research in Neurogeriatrics, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, GermanyTherapy Research in Neurogeriatrics, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, GermanyThe accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson’s disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Syn. This potentially demonstrates an already existing, naturally decomposing, and protective system. Thus, quantitative or qualitative alterations, such as the modified antigen binding of so-called naturally occurring autoantibodies against α-Syn (nAbs-α-Syn), may induce disease onset and/or progression. We investigated the serum titers and binding characteristics of nAbs-α-Syn in patients suffering from sporadic Parkinson’s disease (n = 38), LRRK2 mutation carriers (n = 25), and healthy controls (n = 22). Methods: Titers of nAbs-α-Syn were assessed with ELISA and binding affinities and kinetics with SPR. Within the patient cohort, we discriminated between idiopathic and genetic (LRRK2-mutated) variants. Results: ELISA experiments revealed no significant differences in nAbs-α-Syn serum titers among the three cohorts. Moreover, the α-Syn avidity of nAbs-α-Syn was also unchanged. Conclusions: Our findings indicate that nAbs-α-Syn concentrations or affinities in healthy and diseased persons do not differ, independent of mutations in LRRK2.https://www.mdpi.com/2218-273X/13/9/1303alpha-synucleinnaturally occurring autoantibodiesParkinson’s diseaseLRRK2PARK8 |
| spellingShingle | Alexandra Albus Yannick Kronimus Monika Burg-Roderfeld Hendrik van der Wurp Dieter Willbold Tamar Ziehm Richard Dodel Jean Alexander Ross The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease Biomolecules alpha-synuclein naturally occurring autoantibodies Parkinson’s disease LRRK2 PARK8 |
| title | The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease |
| title_full | The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease |
| title_fullStr | The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease |
| title_full_unstemmed | The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease |
| title_short | The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease |
| title_sort | avidity of autoreactive alpha synuclein antibodies in leucine rich repeat kinase 2 mutation carriers is not altered compared to healthy controls or patients with parkinson s disease |
| topic | alpha-synuclein naturally occurring autoantibodies Parkinson’s disease LRRK2 PARK8 |
| url | https://www.mdpi.com/2218-273X/13/9/1303 |
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