Lower lymphocyte count is associated with increased risk of Parkinson’s disease

With your already increased risk of Parkinsons you'll want your doctor to ameliorate this possible problem.  It is YOUR DOCTOR'S RESPONSIBILITY to prevent Parkinsons.

Parkinson’s Disease May Have Link to Stroke March 2017 

The latest here:

Lower lymphocyte count is associated with increased risk of Parkinson’s disease

Melanie P Jensen (MBBS)

Benjamin Meir Jacobs (MRCP)

Ruth Dobson (MRCP; PhD)

Sara Bandres‐Ciga (PhD)

Cornelis Blauwendraat (PhD)

Anette Schrag (MD; PhD)

… See all authors

First published: 02 February 2021

https://doi.org/10.1002/ana.26034

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.26034.

Abstract

Objectives: 

Patients with established Parkinson’s disease (PD) display differences in
peripheral blood biomarkers of immune function, including leukocyte differential counts, compared to controls. These differences may be useful biomarkers to predict PD and shed light on pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with increased risk of subsequent PD diagnosis.

Methods: 

We examined the relationship between incident PD and baseline differential leukocyte count and other blood markers of acute inflammation in UK Biobank, a longitudinal cohort with >500 000 participants. We used a range of sensitivity analyses and Mendelian randomization (MR) to further explore the nature of associations.

Results: 

After excluding individuals with comorbidities which could influence biomarkers of inflammation, 465 incident PD cases and 312,125 controls remained. Lower lymphocyte count was associated with increased risk of subsequent PD diagnosis (per 1-SD decrease in lymphocyte count OR 1.18, 95% CI 1.07-1.32, p adjusted=0.01). There was some evidence that reductions in eosinophil and monocyte counts and CRP were associated with increased PD risk, as was higher neutrophil count. Only the association between lower lymphocyte count and increased PD risk remained robust to sensitivity analyses. MR suggested that the effect of lower lymphocyte count on PD risk may be causal (per 1-SD decrease in lymphocyte count; OR MR 1.09, 95% CI 1.01-1.18, p=0.02).

Interpretation: 

We provide converging evidence from observational analyses in UKB and MR that lower lymphocyte count is associated with an increased risk of subsequent PD.

Introduction 

Parkinson’s disease (PD) affects 2% of the population over 65.¹The diagnosis is made once motor signs appear, however by this stage ~50% of nigrostriatal neurons have been lost.²There is an urgent unmet clinical need for earlier identification of PD and development of therapies which could slow, prevent, or reverse the progression of the disease. Immune dysregulation may play a role in the pathogenesis of PD. The white blood cell(WBC) differential is a crude marker of immune function but is simple to measure in large scale observational studies. Previous studies have found lower lymphocyte counts in PD patients compared with controls, driven by reductions in helper-CD4+, rather than cytotoxic-CD8+, T-cell and B-cells counts.^3-7Case-control studies have also identified higher neutrophil and lower lymphocyte counts in patients with established PD compared with controls.⁸Converging evidence from genetic, epidemiological, and cytokine profiling studies has added further weight to the view that immune dysregulation may play a role in the pathogenesis of PD.⁹Human Leukocyte Antigen genes (HLA-DRB1/DRB5) have been identified as risk loci for PD in genome-wide association studies (GWAS).^{10, 11}In vitro, alpha-synuclein-derived peptides are preferentially displayed on major histocompatibility (MHC) molecules associated with PD risk, suggesting that PD-associated HLA haplotypes could drive an adaptive immune response targeted towards alpha-synuclein epitopes.^{12, 13}Variants in the leucine-rich repeat kinase 2 (LRRK2) gene, a target for proinflammatory signals, confer effects in the same direction on risk of PD and Crohn’s disease.¹⁴Observational studies have reported reduced risk of PD and reduced penetrance in LRRK2-associated PD with use of immunosuppressants and non-steroidal anti-inflammatory drugs.^{15, 16}The prospective ICICLE-PD cohort study found that a baseline ‘pro-inflammatory’ cytokine serum profile in PD patients was associated with faster motor deterioration than an ‘anti-inflammatory’ profile.¹⁷