Capillary Dysfunction and CD46-immunoreceptor (CD46) Type in MS

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

This project aims to contribute knowledge to early MS disease mechanisms at the brain-blood interface using a combined immunological and neuroimaging approach.

The aim is to provide a novel vascular model to assess MS disease activity, and to explore its potential as an early diagnostic biomarker, prior to blood-brain barrier disruption. Additionally, the investigators want to investigate influence of immune receptor defects upon disease activity and MS brain vascular system. These aims are addressed by investigating immune receptor signals and vascular imaging modalities acquired in newly diagnosed untreated MS cohort, followed at our institution.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Diagnostic test: Diagnostic criteria for MS

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 83

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark
    • Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients are recruited consecutively on admission for diagnostic investigations to the MS clinic, Department of Neurology, Aarhus University Hospital

Description

Inclusion Criteria:

Patients > 18 years Patients suspected with MS.

Exclusion Criteria:

Pregnancy. Drug/alcohol abuse. Cerebral tumor. Previous head injury. Previous use of immunosuppressing or modifying treatment within 6 months. Contraindications against contrast media. Baseline image analysis not available.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS patients/cases; Patients admitted for diagnostic investigations to the MS clinic were offered participation if aged >18 years and no previous use of immunosuppressing or modifying drugs within 6 months. The diagnosis healthy/diseased was made by 2017 Mc Donald criteria.	Diagnostic test: Diagnostic criteria for MS; The diagnosis healthy/diseased was made by 2017 Mc Donald criteria.
Healthy subjects/controls; Patients admitted for diagnostic investigations to the MS clinic were offered participation if aged >18 years and no previous use of immunosuppressing or modifying drugs within 6 months. The diagnosis healthy/diseased was made by 2017 Mc Donald criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Capillary dysfunction	DSC- metric	Baseline
CD46 dysfunction	CD46 immune receptor phenotype and function	Baseline

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Linda Sundvall, MD, Department of Neurology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 8, 2019

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis
• Other Study ID Numbers: MS_CD46_MRI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No