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

• Published in: Journal of neuroinflammation Vol. 17; no. 1; p. 349
• Main Authors: 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, Robertson, Neil P., Gran, Bruno, Kee, Rachael, Hughes, Stella, McDonnell, Gavin, Howell, Owain, Fitzgerald, Denise C.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.11.2020; BioMed Central
• Subjects: Adult; Aged; Aged, 80 and over; Astrocytes; Blood vessels; Body mass index; Brain - drug effects; Brain - metabolism; Brain research; CD4 antigen; Cell interaction; Central nervous system; Cerebrospinal fluid; Cohort Studies; Disease; Disease Progression; Enzyme-linked immunosorbent assay; Ethics; Female; Gene expression; Genetic aspects; Humans; Hybridization; Immune response; Immunoreactivity; Interferon-beta - therapeutic use; Lymphocytes; Lymphocytes T; Male; Middle Aged; Monoclonal antibodies; mRNA; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - metabolism; Myelin; Natalizumab - therapeutic use; Nephroblastoma Overexpressed Protein - biosynthesis; Nephroblastoma Overexpressed Protein - genetics; Plasma; Proteins; R&D; Regeneration; Research & development; Treatment Outcome; Weight control; β-Interferon; United Kingdom; Plasma; Multiple sclerosis; CCN3; Myelin; CSF
• DOI: 10.1186/s12974-020-02025-7
• ISSN: 1742-2094

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. 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. 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. 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.