Naughton, Michelle and Moffatt, Jill and Eleftheriadis, George and de la Vega Gallardo, Nira and Young, Andrew and Hawkins, Kristen and Pearson, Ben and Perbal, Bernard and Hogan, Andrew E. and Moynagh, Paul N. and Loveless, Sam and Robertson, Neil P. and Gran, Bruno and Kee, Rachael and Hughes, Stella and McDonnell, Gavin and Howell, Owain and Fitzgerald, Denise C. (2020) CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis. Journal of Neuroinflammation, 17 (349). pp. 1-13. ISSN 1742-2094

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Abstract

Background: Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods: CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results: Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions: This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.

Item Type:	Article
Keywords:	Multiple sclerosis; CCN3; Myelin; Plasma; CSF;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	14912
Identification Number:	https://doi.org/10.1186/s12974-020-02025-7.
Depositing User:	Andrew Hogan
Date Deposited:	11 Oct 2021 12:20
Journal or Publication Title:	Journal of Neuroinflammation
Publisher:	Springer Nature
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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