The Association Between Capillary Dysfunction and CD46 Phenotype in Early Diagnosed MS Patients

Multiple sclerosis (MS) is considered a virus-mediated autoimmune disease in the central nerve system characterized by blood brain barrier (BBB) disruption. Conventional magnetic resonance imaging (MRI) is currently an invaluable diagnostic tool as structural lesions are accepted biomarkers. However, MRI lesions correlate poorly with disease burden underlining the clinical-radiological paradox. Therefore, more advanced MRI are needed to provide additional information beyond what is obtainable from conventional scans. Perfusion MRI alterations preceding overt BBB disruption and lesions have been described suggesting a microvascular pathology as an etiological contributor to MS lesions. Transient diffusion decrease observed by diffusion MRI support the hypothesis of a hypoxic event prior to BBB disruption. A new model of perfusion MRI (DSC) enables microvascular function assessment in MS. This model is yet to be tested on MS patients. Furthermore, emerging evidence suggest that virus receptor CD46 affects immunologic susceptibility to MS. CD46 is highly expressed on cerebral vascular endothelium and may protect BBB integrity.

The hypothesis for this project is that CD46 activity is modulator of MS disease development, where CD46 modifications increases vulnerability to BBB disruption by attenuation of normal flow responses in MS brains.

Aims: Besides testing correlations between microvascular dysfunction and MS clinical outcome, this have prompted the investigators to investigate DSC-metric and predicted microvascular dysfunction in relation to defective CD46-driven immune responses.

Method: For this the investigators conducted our MRI study performed in a clinical research setting, and the - immunological study performed in a laboratory setting. Both studies are based on newly diagnosed MS patient assessments conducted at Department of Neurology, Aarhus University Hospital. All subjects undergo clinical examination, blood/cerebrospinal fluid samples and a comprehensive 3Tesla (3T) MRI protocol. MRI parameters and immune responses are compared between study groups and related to clinical outcome.