Frontiers in Neurology (Dec 2018)
Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease
- Rezzak Yilmaz,
- Antonio P. Strafella,
- Antonio P. Strafella,
- Antonio P. Strafella,
- Antonio P. Strafella,
- Antonio P. Strafella,
- Antonio P. Strafella,
- Alice Bernard,
- Claudia Schulte,
- Claudia Schulte,
- Lieneke van den Heuvel,
- Lieneke van den Heuvel,
- Nicole Schneiderhan-Marra,
- Thomas Knorpp,
- Thomas O. Joos,
- Frank Leypoldt,
- Frank Leypoldt,
- Johanna Geritz,
- Clint Hansen,
- Sebastian Heinzel,
- Anja Apel,
- Anja Apel,
- Thomas Gasser,
- Thomas Gasser,
- Anthony E. Lang,
- Anthony E. Lang,
- Anthony E. Lang,
- Anthony E. Lang,
- Anthony E. Lang,
- Daniela Berg,
- Daniela Berg,
- Daniela Berg,
- Walter Maetzler,
- Walter Maetzler,
- Walter Maetzler,
- Connie Marras,
- Connie Marras
Affiliations
- Rezzak Yilmaz
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Antonio P. Strafella
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Antonio P. Strafella
- Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University of Toronto, Toronto, ON, Canada
- Antonio P. Strafella
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- Antonio P. Strafella
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Antonio P. Strafella
- Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Hospital Network, University of Toronto, Toronto, ON, Canada
- Antonio P. Strafella
- Krembil Brain Institute, University Health Network, Toronto, ON, Canada
- Alice Bernard
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Claudia Schulte
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Claudia Schulte
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Lieneke van den Heuvel
- Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University of Toronto, Toronto, ON, Canada
- Lieneke van den Heuvel
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- Nicole Schneiderhan-Marra
- 0Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany
- Thomas Knorpp
- 0Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany
- Thomas O. Joos
- 0Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany
- Frank Leypoldt
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Frank Leypoldt
- 1Neuroimmunology, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany
- Johanna Geritz
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Clint Hansen
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Sebastian Heinzel
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Anja Apel
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Anja Apel
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Thomas Gasser
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Thomas Gasser
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Anthony E. Lang
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Anthony E. Lang
- Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University of Toronto, Toronto, ON, Canada
- Anthony E. Lang
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- Anthony E. Lang
- Krembil Brain Institute, University Health Network, Toronto, ON, Canada
- Anthony E. Lang
- 2Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
- Daniela Berg
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Daniela Berg
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Daniela Berg
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Walter Maetzler
- Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Walter Maetzler
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Walter Maetzler
- German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
- Connie Marras
- Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University of Toronto, Toronto, ON, Canada
- Connie Marras
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- DOI
- https://doi.org/10.3389/fneur.2018.01123
- Journal volume & issue
-
Vol. 9
Abstract
Background: Blood levels of immune markers have been proposed to 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 phenotypes 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
