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Characterising Natural Killer cells in early Parkinson’s disease

J. Holbrook, B. Patel, M. Camacho, C. Williams-Gray (Cambridge, United Kingdom)

Meeting: 2022 International Congress

Abstract Number: 1359

Keywords: Inflammation, Parkinson’s

Category: Parkinson's Disease: Molecular Mechanisms of Disease

Objective: To determine whether the number and phenotype of Natural Killer (NK) cells in the blood is altered in early Parkinson’s disease (PD).

Background: Accumulating evidence implicates immune dysregulation as a component of the development and progression of PD. Genome-wide association studies demonstrate association between multiple immune-related loci and PD, epidemiological studies indicate that use of anti-immunosuppressive and anti-inflammatory drugs reduces risk of developing PD, and a pro-inflammatory cytokine profile is associated with faster disease progression. Moreover, α-synuclein induces an immune response in vitro.
Changes in several immune cell types have been demonstrated in PD, particularly early in disease course. However, the precise immune cell types and mechanisms which are of most relevance to PD progression remain to be determined. NK cells are innate immune cells that specialise in the targeting and destruction of malignant or infected cells; upon activation they bind to and induce lysis of the target cell via the release of perforin and granzymes. They have thus far been only superficially investigated as to the role they may play in PD development and progression. This study aims to characterise NK cells in the blood in the early stages of PD and determine whether their profile is altered compared to age-matched controls.

Method: Venous blood samples are collected from PD and healthy controls (HC). Peripheral blood mononuclear cells (PBMCs) are isolated and immunostained with a panel of antibodies for surface markers on NK cells prior to analysis with flow cytometry. NK cells are identified as CD3- CD56+, with additional markers CD16, CD57, NKG2A, and NKG2D being used to distinguish potentially relevant NK cell subsets. NKT cells are also defined as CD3+ CD56+.
Inclusion criteria are age 55 – 80 years, < 2 years since PD diagnosis, Hoehn and Yahr </= 2, exclusion criteria were use of immunomodulatory drugs or autoimmune/inflammatory conditions. The target sample size is 20 HC and 20 PD.

Results: Preliminary data indicate a trend towards an increase in NK cells as a percentage of the total lymphocyte population. Further data collection is ongoing.

Conclusion: More in-depth immunophenotyping of NK cells is warranted, as NK cells remain an understudied immune cell type in PD and could represent a target for future immunotherapies.

To cite this abstract in AMA style:

J. Holbrook, B. Patel, M. Camacho, C. Williams-Gray. Characterising Natural Killer cells in early Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/characterising-natural-killer-cells-in-early-parkinsons-disease/. Accessed June 15, 2025.
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