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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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Autores principales: Albus, Alexandra, Kronimus, Yannick, Burg-Roderfeld, Monika, van der Wurp, Hendrik, Willbold, Dieter, Ziehm, Tamar, Dodel, Richard, Ross, Jean Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526238/
https://www.ncbi.nlm.nih.gov/pubmed/37759704
http://dx.doi.org/10.3390/biom13091303
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author Albus, Alexandra
Kronimus, Yannick
Burg-Roderfeld, Monika
van der Wurp, Hendrik
Willbold, Dieter
Ziehm, Tamar
Dodel, Richard
Ross, Jean Alexander
author_facet Albus, Alexandra
Kronimus, Yannick
Burg-Roderfeld, Monika
van der Wurp, Hendrik
Willbold, Dieter
Ziehm, Tamar
Dodel, Richard
Ross, Jean Alexander
author_sort Albus, Alexandra
collection PubMed
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.
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spelling pubmed-105262382023-09-28 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 Albus, Alexandra Kronimus, Yannick Burg-Roderfeld, Monika van der Wurp, Hendrik Willbold, Dieter Ziehm, Tamar Dodel, Richard Ross, Jean Alexander Biomolecules Brief Report 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. MDPI 2023-08-25 /pmc/articles/PMC10526238/ /pubmed/37759704 http://dx.doi.org/10.3390/biom13091303 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Albus, Alexandra
Kronimus, Yannick
Burg-Roderfeld, Monika
van der Wurp, Hendrik
Willbold, Dieter
Ziehm, Tamar
Dodel, Richard
Ross, Jean Alexander
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 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 Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526238/
https://www.ncbi.nlm.nih.gov/pubmed/37759704
http://dx.doi.org/10.3390/biom13091303
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