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. 2023 Aug 25;13(9):1303. doi: 10.3390/biom13091303.

Abstract

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.

Keywords: LRRK2; PARK8; Parkinson’s disease; alpha-synuclein; naturally occurring autoantibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies
  • Humans
  • Leucine
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / genetics
  • Mutation
  • Parkinson Disease* / genetics
  • alpha-Synuclein* / immunology

Substances

  • alpha-Synuclein
  • Autoantibodies
  • Leucine
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

Grants and funding

This study was supported by the Michael J. Fox Foundation. The publication is supported by the Open Access Publication Fund of the University of Duisburg-Essen.