Phenotypic and Functional Study of 4BL B Cells in Multiple Sclerosis (MS) (4BLMS)

Recent works highlight the B cells involvement in multiple sclerosis (MS) pathology but their role remains poorly understood. It was previously described that activated memory B cells called 4BL due to the increased expression of 4-1BBL, an activation marker, induce pro-inflammatory response by activating T CD8+ lymphocytes. Those 4BL cells are also described in systemic inflammation in 80 years old people explaining the poor efficiency of vaccination in that sub population. Those 4BL cells can also induce anti-tumoral T cell response.

The hypothesize is that 4BL may induce a pathogenic inflammatory response in MS.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis

Detailed Description

the aim to compare the proportion of peripheral (blood) 4 BL cells but also 4-BL cells in cerebro spinal fluid (CSF) in MS compared to healthy controls and to other inflammatory neurological disease but also non inflammatory neurological disease.

For all groups of patients and controls it will collect blood and CSF only once (at diagnosis time for patients).

Blood collect from healthy controls will come from transfusion volunteers and we won't have CSF from them.

For patients from the MS group, the blood collect will be sequential at diagnosis, 3, 6, 12 and 24 months after during the follow up.

In the blood and CSF we will evaluate:

• percentage of 4 BL cells. 4 BL cells are found using cytometric parameters
• capacity of 4 BL cells to induce inflammatory response in vitro: percentage of induced activated TCD8 proliferation after cell culture using extracellular and intracellular cytometric parameters

• Study Type: Observational
• Enrollment (Anticipated): 172

Contacts and Locations

• Study Contact: Name: Hélène ZEPHIR, MD, PhD; Phone Number: +33 3 20 44 68 46; Email: helene.zephir@chru-lille.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

MS patients and controls: healthy controls and patients having non-MS neurological inflammatory disease and patients having other non inflammatory neurological disease.

Description

Inclusion Criteria for MS group:

• MS defined by McDonald 2017 criteria with a disease duration of less than 1 year
• between 18 and 60 years old patients
• naïve of any immune therapy or steroid intake
• patients who signed consent to the study

Inclusion Criteria for controls with inflammatory of non inflammatory neurological disease:

• patients who signed consent to the study
• between 18 and 60 years old patients
• naïve of any steroid intake or immune therapy

Inclusion criteria for healthy controls:

• control who signed consent at transfusion center for their blood collect to be used for study
• between 18 and 60 years old patients
• naïve of any steroid intake or immune therapy

Exclusion Criteria:

• pregnancy or breast-feeding
• patients or controls unable to sign the consent or to consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
multiple sclerosis patient; MS is defined according to McDonald criteria 2017. MS patients included have a disease duration of less than 1 year
other neurological inflammatory disease; autoimmune encephalitis, myasthenia gravis, chronic inflammatory demyelinating polyradiculitis
neurological non inflammatory disease; benign intracranial hypertension, degenerative disorder
healthy controls; transfusion volunteers from transfusion center

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage of 4 BL cells in blood between MS patients and healthy controls	4 BL are defined using cytometric parameters	Baseline: one session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage of 4 BL cells in blood between MS patients and patients with inflammatory and non inflammatory neurological disease	4 BL are defined using cytometric parameters	Baseline: one session
the percentage of 4 BL cells in CSF between MS patients and patients with inflammatory and non inflammatory neurological disease	4 BL are defined using cytometric parameters	Baseline: one session
to analyse over time the evolution of 4BL percentages in blood in MS patients	4 BL are defined using cytometric parameters	5 blood collection at baseline, 3, 6, 12, and 24 months after baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biological bank with mononuclear cells from all the groups fo that study	to constitute at Baseline a biological bank with mononuclear cells from all the groups fo that study	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Hélène Zephir, MD, PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: immunology; B cells
• 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: 2016_04; 2017-A00835-48 (Other Identifier: ID-RCB number, ANSM)

Drug and device information, study documents

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