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

Williams-Gray, Caroline H; Wijeyekoon, Ruwani; Yarnall, Alison J; Lawson, Rachael A; Breen, David P; Evans, Jonathan R; Cummins, Gemma A; Duncan, Gordon W; Khoo, Tien K and Burn, David J, et al. (2016) In Movement Disorders 31(7). p.995-1003
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... (More)

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. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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published
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keywords
Serum immune markers, Parkinson disease
in
Movement Disorders
volume
31
issue
7
pages
9 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:84977581059
  • wos:000379942900014
ISSN
0885-3185
DOI
10.1002/mds.26563
language
English
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yes
id
cc2b3aca-e25e-4f3d-baf6-eb020df7bba3
date added to LUP
2016-11-23 13:11:11
date last changed
2017-11-14 09:52:44
@article{cc2b3aca-e25e-4f3d-baf6-eb020df7bba3,
  abstract     = {<p>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.</p><p>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.</p><p>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 &lt; 0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P &lt; 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).</p><p>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. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</p>},
  author       = {Williams-Gray, Caroline H and Wijeyekoon, Ruwani and Yarnall, Alison J and Lawson, Rachael A and Breen, David P and Evans, Jonathan R and Cummins, Gemma A and Duncan, Gordon W and Khoo, Tien K and Burn, David J and Barker, Roger A and , },
  issn         = {0885-3185},
  keyword      = {Serum immune markers,Parkinson disease},
  language     = {eng},
  number       = {7},
  pages        = {995--1003},
  publisher    = {John Wiley & Sons},
  series       = {Movement Disorders},
  title        = {Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)},
  url          = {http://dx.doi.org/10.1002/mds.26563},
  volume       = {31},
  year         = {2016},
}