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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.01123

Serum inflammatory profile for the discrimination of clinical subtypes in Parkinson’s disease

 Rezzak Yilmaz1, Antonio Strafella2, Alice Bernard3,  Claudia Schulte3,  Lieneke van den Huevel4,  Nicole Schneiderhan-Marra5, Thomas Knorpp5, Thomas Joos5,  Frank Leypoldt1,  Johanna Geritz1*,  Clint Hansen1, Anja Apel3, Thomas Gasser3, Anthony Lang2,  Daniela Berg1,  Walter Maetzler1 and Connie Marras6
  • 1Department of Neurology, Christian-Albrechts-University of Kiel, Germany
  • 2Institute of Medical Science, University of Toronto, Canada
  • 3Hertie-Institut für klinische Hirnforschung (HIH), Germany
  • 4Toronto Western Hospital, Canada
  • 5Natural and Medical Sciences Institute, Germany
  • 6Division of Neurology, Department of Medicine, University of Toronto, Canada

Background: Blood levels of immune markers discriminate patients with Parkinson’s disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified.
Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients.
Methods: Phenotypes of clinical PD from Tübingen, Germany (n=145) and Toronto, Canada (n=90) were defined regarding clinical subtype, disease onset, severity and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical subtype after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in-vivo brain microglial activation.
Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET.
Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes.

Keywords: Parkinson’s disease, Immune markers, Interleukins, Cytokines, Parkinsion's disease subtypes

Received: 08 Sep 2018; Accepted: 06 Dec 2018.

Edited by:

Tobias Warnecke, University Hospital Münster, Germany

Reviewed by:

Nico Melzer, University of Münster, Germany
Avner Thaler, Tel Aviv Sourasky Medical Center, Israel
Stefan Bittner, Johannes Gutenberg University Mainz, Germany  

Copyright: © 2018 Yilmaz, Strafella, Bernard, Schulte, van den Huevel, Schneiderhan-Marra, Knorpp, Joos, Leypoldt, Geritz, Hansen, Apel, Gasser, Lang, Berg, Maetzler and Marras. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ms. Johanna Geritz, Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Schleswig-Holstein, Germany, j.geritz@neurologie.uni-kiel.de