Skip to main content
Top
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Parkinson's Disease | Letter to the Editor

Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease

Authors: Caroline Perner, Florian Perner, Nayana Gaur, Silke Zimmermann, Otto W. Witte, Florian H. Heidel, Julian Grosskreutz, Tino Prell

Published in: Journal of Neuroinflammation | Issue 1/2019

Login to get access

Abstract

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. There is increasing evidence that PD pathology is accompanied by an inflammatory response. This is highly relevant for understanding disease progression and the development of novel neuroprotective therapies.

Objective

Assessing potential dysregulation of a panel of inflammatory mediators in the peripheral blood mononuclear cells (PBMCs) and plasma of PD patients and in the context of clinical outcome metrics.

Methods

We performed a screening of selected cell-surface chemokine receptors and adhesion molecules in PBMCs from PD patients and age-matched healthy controls in a flow cytometry-based assay. ELISA was used to quantify VCAM1 levels in the plasma of PD patients. Lymphocytic chemotactic ability was assessed using a modified Boyden chamber assay.

Results

VLA4 expression was significantly downregulated on CD3+ T cells, CD56+ NK cells, and CD3+/CD56+ NK-T cells from PD patients; further, an increase of the soluble VLA4 ligand VCAM1 in patient plasma was noted. sVCAM1 in PD patients was even higher than reported for patients with multiple sclerosis, neuromyelitis optica, and rheumatoid arthritis. sVCAM1 levels correlated with the disease stage (Hoehn and Yahr scale) and motor impairment. Chemoattraction with SDF-1α revealed impaired motility of lymphocytes from PD patients relative to controls.

Conclusion

Our data provides evidence for a functional dysregulation of the sVCAM1-VLA4 axis in PD. Further studies evaluating the therapeutic potential of this axis are warranted.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124:901–5.CrossRef Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124:901–5.CrossRef
2.
go back to reference Brochard V, Combadiere B, Prigent A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119:182–92.PubMed Brochard V, Combadiere B, Prigent A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119:182–92.PubMed
3.
go back to reference Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918–34.CrossRef Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918–34.CrossRef
4.
go back to reference Perner C, Perner F, Stubendorff B, et al. Dysregulation of chemokine receptor expression and function in leukocytes from ALS patients. J Neuroinflammation. 2018;15:99.CrossRef Perner C, Perner F, Stubendorff B, et al. Dysregulation of chemokine receptor expression and function in leukocytes from ALS patients. J Neuroinflammation. 2018;15:99.CrossRef
5.
go back to reference Navarro-Hernandez RE, Oregon-Romero E, Vazquez-Del Mercado M, Rangel-Villalobos H, Palafox-Sanchez CA, Munoz-Valle JF. Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical activity. Association with genetic polymorphisms. Dis Markers. 2009;26:119–26.CrossRef Navarro-Hernandez RE, Oregon-Romero E, Vazquez-Del Mercado M, Rangel-Villalobos H, Palafox-Sanchez CA, Munoz-Valle JF. Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical activity. Association with genetic polymorphisms. Dis Markers. 2009;26:119–26.CrossRef
6.
go back to reference Kalinowska-Lyszczarz A, Michalak S, Pawlak MA, Losy J, Kozubski W. Serum sPECAM-1 and sVCAM-1 levels are associated with conversion to multiple sclerosis in patients with optic neuritis. J Neuroimmunol. 2016;300:11–4.CrossRef Kalinowska-Lyszczarz A, Michalak S, Pawlak MA, Losy J, Kozubski W. Serum sPECAM-1 and sVCAM-1 levels are associated with conversion to multiple sclerosis in patients with optic neuritis. J Neuroimmunol. 2016;300:11–4.CrossRef
7.
8.
go back to reference Tchalla AE, Wellenius GA, Sorond FA, et al. Elevated soluble vascular cell adhesion molecule-1 is associated with cerebrovascular resistance and cognitive function. J Gerontol A Biol Sci Med Sci. 2017;72:560–6.PubMed Tchalla AE, Wellenius GA, Sorond FA, et al. Elevated soluble vascular cell adhesion molecule-1 is associated with cerebrovascular resistance and cognitive function. J Gerontol A Biol Sci Med Sci. 2017;72:560–6.PubMed
9.
go back to reference Skorvanek M, Martinez-Martin P, Kovacs N, et al. Differences in MDS-UPDRS scores based on Hoehn and Yahr stage and disease duration. Mov Disord Clin Pract. 2017;4:536–44.CrossRef Skorvanek M, Martinez-Martin P, Kovacs N, et al. Differences in MDS-UPDRS scores based on Hoehn and Yahr stage and disease duration. Mov Disord Clin Pract. 2017;4:536–44.CrossRef
10.
go back to reference Herlofson K, Heijnen CJ, Lange J, et al. Inflammation and fatigue in early, untreated Parkinson’s disease. Acta Neurol Scand. 2018. Herlofson K, Heijnen CJ, Lange J, et al. Inflammation and fatigue in early, untreated Parkinson’s disease. Acta Neurol Scand. 2018.
11.
go back to reference George G, Valiya Parambath S, Lokappa SB, Varkey J. Construction of Parkinson’s disease marker-based weighted protein-protein interaction network for prioritization of co-expressed genes. Gene. 2019;697:67–77.CrossRef George G, Valiya Parambath S, Lokappa SB, Varkey J. Construction of Parkinson’s disease marker-based weighted protein-protein interaction network for prioritization of co-expressed genes. Gene. 2019;697:67–77.CrossRef
Metadata
Title
Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease
Authors
Caroline Perner
Florian Perner
Nayana Gaur
Silke Zimmermann
Otto W. Witte
Florian H. Heidel
Julian Grosskreutz
Tino Prell
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1482-8

Other articles of this Issue 1/2019

Journal of Neuroinflammation 1/2019 Go to the issue