An Observational Study to Investigate the Role of B Cells in Multiple Sclerosis

Decoding the B Cell Response in Multiple Sclerosis

Multiple sclerosis (MS) typically afflict young people in their twenties, when they start a career and establish a family. The disease thus imposes a severe impact on quality of life and heavy economic burdens on society. Critical barriers to progress in the field are the lack of knowledge of relevant immune cell subsets driving the pathology and the targets of the immune response within the central nervous system. In this project, we will test the hypothesis that a subgroup of MS patients is defined by a genetically determined B cell response against specific antigenic epitopes. The hypothesis is based on our recent, pioneering results showing that approximately half of MS patients have a restricted population of B cells in the cerebrospinal fluid defined by polymorphisms in the constant heavy-chain of the immunoglobulin B cell receptor, the G1m1 allotype. Here, we aim to characterize the G1m1 B cells, to disentangle the genetic basis of the B cell response, and to identify the molecular targets.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Analysis of B cells

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Andreas Lossius, MD, PhD; Phone Number: +47 93068515; Email: postmottak@medisin.uio.no

Study Locations

• Norway
  • Lørenskog, Norway
    • Recruiting
    • Akershus University Hospital
    • Contact: Trygve Holmøy, MD, PhD; Phone Number: +4767960000; Email: postmottak@ahus.no
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Pål Berg-Hansen; Phone Number: +47 22118080; Email: post@oslo-universitetssykehus.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients under diagnostic work-up for multiple sclerosis.

Description

Inclusion Criteria:

• Symptoms and brain MRI scans strongly suggestive of multiple sclerosis according to the 2017 McDonald revisions
• Intrathecal immunoglobulin G synthesis
• Age > 18 years

Exclusion Criteria:

• Treatment with immunomodulatory drugs

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Multiple sclerosis; Patients with relapsing-remitting multiple sclerosis	Other: Analysis of B cells; B cells from blood and cerebrospinal fluid will be analyzed using RNA-seq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The transcriptome of B cells from blood and cerebrospinal fluid	1 day (subject inclusion)
The immunglobulin receptors of B cells from blood and cerebrospinal fluid	1 day (subject inclusion)

Collaborators and Investigators

• Sponsor: University of Oslo
• Investigators: Principal Investigator: Andreas Lossius, University of Oslo

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 5, 2018
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (ACTUAL): July 16, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 314376 - FORSKER20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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