Longitudinal cytokines in plasma extracellular vesicle enriched preparations and motor worsening in Parkinson disease
5 affiliations
- 1Department of Neurology, Taipei Medical University-Shuang Ho Hospital
- 2Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University
- 3Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University
- 4Melbourne School of Psychological Sciences, The University of Melbourne
- 5Melbourne Brain Centre for Imaging Unit, The University of Melbourne
Abstract
Introduction: Inflammation is implicated in Parkinson disease (PD), but the prognostic value of circulating cytokines beyond clinical information remains incompletely defined.
Methods: We studied cytokines measured in polymer-precipitated plasma extracellular vesicle (EV)-enriched preparations in a longitudinal cohort of 62 participants with PD; 21 healthy controls contributed baseline descriptive data. Fifteen cytokines were assessed using multiplex immunoassays. Contemporaneous cytokine -clinical score associations were examined using covariate-adjusted generalized estimating equations (GEE) with false discovery rate (FDR) correction. Prediction analyses used 147 consecutive follow-up intervals, with worsening defined as an increase of at least three points in the original Unified Parkinson's Disease Rating Scale Part III. ON-medication status for motor examinations was confirmed by patient report; exact dose-to-assessment intervals were not recorded. Clinical-only, cytokine-only and combined radial basis function support vector machine (RBF-SVM) models were compared using participant-grouped nested cross-validation.
Results: Eight of 105 cytokine-by-visit interactions met the FDR threshold after adjustment including baseline disease duration. Clinical-only, cytokine-only and combined pooled out-of-fold areas under the curve (AUCs) were 0.733, 0.722 and 0.784, respectively. The combined-minus-clinical AUC difference was 0.051 (95% confidence interval −0.009 to 0.112). At the five-point sensitivity threshold, the corresponding AUCs were 0.743, 0.675 and 0.790, with a difference of 0.047 (−0.023 to 0.112).
Discussion: Cytokines in EV-enriched preparations showed visit-dependent clinical associations and numerically higher discrimination when combined with clinical predictors within the RBF-SVM framework. Independent validation and matched conventional plasma measurements are needed to determine clinical usefulness and preparation-specific value.
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BibTeX
@article{hong2026longitudinal,
title = {{Longitudinal cytokines in plasma extracellular vesicle enriched preparations and motor worsening in Parkinson disease}},
author = {Chien-Tai Hong and Yi-Chen Hsieh and Lung Chan and Wei-Ting Chiu and Chin-Hsuan Sophie Lin and Chen-Chih Chung},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1973023},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973023/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal cytokines in plasma extracellular vesicle enriched preparations and motor worsening in Parkinson disease
AU - Chien-Tai Hong
AU - Yi-Chen Hsieh
AU - Lung Chan
AU - Wei-Ting Chiu
AU - Chin-Hsuan Sophie Lin
AU - Chen-Chih Chung
PY - 2026
DA - 2026/10/21
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1973023
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973023/full
AB - Introduction: Inflammation is implicated in Parkinson disease (PD), but the prognostic value of circulating cytokines beyond clinical information remains incompletely defined. Methods: We studied cytokines measured in polymer-precipitated plasma extracellular vesicle (EV)-enriched preparations in a longitudinal cohort of 62 participants with PD; 21 healthy controls contributed baseline descriptive data. Fifteen cytokines were assessed using multiplex immunoassays. Contemporaneous cytokine -clinical score associations were examined using covariate-adjusted generalized estimating equations (GEE) with false discovery rate (FDR) correction. Prediction analyses used 147 consecutive follow-up intervals, with worsening defined as an increase of at least three points in the original Unified Parkinson's Disease Rating Scale Part III. ON-medication status for motor examinations was confirmed by patient report; exact dose-to-assessment intervals were not recorded. Clinical-only, cytokine-only and combined radial basis function support vector machine (RBF-SVM) models were compared using participant-grouped nested cross-validation. Results: Eight of 105 cytokine-by-visit interactions met the FDR threshold after adjustment including baseline disease duration. Clinical-only, cytokine-only and combined pooled out-of-fold areas under the curve (AUCs) were 0.733, 0.722 and 0.784, respectively. The combined-minus-clinical AUC difference was 0.051 (95% confidence interval −0.009 to 0.112). At the five-point sensitivity threshold, the corresponding AUCs were 0.743, 0.675 and 0.790, with a difference of 0.047 (−0.023 to 0.112). Discussion: Cytokines in EV-enriched preparations showed visit-dependent clinical associations and numerically higher discrimination when combined with clinical predictors within the RBF-SVM framework. Independent validation and matched conventional plasma measurements are needed to determine clinical usefulness and preparation-specific value.
SN - 1664-3224
ER -