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CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis

Naughton, Michelle, Moffat, Jill, Eleftheriadis, George, de la Vega Gallardo, Nira, Young, Andrew, Falconer, John, Hawkins, Kristen, Pearson, Ben, Perbal, Bernard, Hogan, Andrew, Moynagh, Paul, Loveless, Sam ORCID:, Robertson, Neil P. ORCID:, Gran, Bruno, Kee, Rachael, Hughes, Stella, McDonnell, Gavin, Howell, Owain and Fitzgerald, Denise C. 2020. CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis. Journal of Neuroinflammation 17 (1) , 349. 10.1186/s12974-020-02025-7

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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. Keywords: Multiple sclerosis, CCN3, Myelin, Plasma, CSF

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: Attribution 4.0 International (CC BY 4.0)
Publisher: BioMed Central
ISSN: 1742-2094
Date of First Compliant Deposit: 15 January 2021
Date of Acceptance: 4 November 2020
Last Modified: 02 May 2023 18:34

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