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Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)

Lookup NU author(s): Dr Alison Yarnall, Dr Rachael Lawson, Dr Gordon Duncan, Dr Tien Kheng Khoo, Professor David Burn

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD. Methods Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale — part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated. Results TNF-α, IL1-β, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P ≤ 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P<0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P<0.05). Multiple linear regression analysis with adjustment for covariates confirmed "anti-inflammatory" component score was the strongest predictor of slower motor progression (β = −0.22, P=0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (β = −0.175, P=0.007). Conclusions Serum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD.


Publication metadata

Author(s): Williams-Gray CH, Wijeyekoon R, Yarnall AJ, Lawson RA, Breen DP, Evans JR, Cummings GA, Duncan GW, Khoo TK, Burn DJ, Barker RA, on behalf of the ICICLE-PD study group

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2016

Volume: 31

Issue: 7

Pages: 995-1003

Print publication date: 01/07/2016

Online publication date: 21/03/2016

Acceptance date: 06/01/2016

Date deposited: 03/05/2016

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/mds.26563

DOI: 10.1002/mds.26563


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