B Cell Differentiation in MS (ABCD-SEP)

Analysis of B Cell Differentiation in Multiple Sclerosis

Interventional study with minimal risks and constraints, prospective, monocentric.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Biological Samples; Other: Biological Samples; Other: Biological Samples; Other: Biological Samples

Detailed Description

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) affecting primarily young adults. This disease is the leading cause of non-traumatic disability in this population.

MS has long been considered as a T-cell mediated disease. However, the remarkable efficacy of anti-CD20 monoclonal antibodies in this disease has highlighted the major role of B-lymphocytes in the pathophysiology of this disease.

Despite many advances made recently in understanding the role of B-lymphocytes in the pathophysiology of MS, the precise involvement of plasma cells and their function at different stages of the disease remains unclear. In this project, the investigators plan to analyze the differentiation abilities of circulating B-lymphocytes in patients with MS.

Follicular helper T cells (TFH) play a crucial role in B lymphocyte differentiation. These cells are located within germinal centers in secondary lymphoid organs, and their memory compartment also circulates in the blood. Several circulating TFH subpopulations have recently been defined, with different helping capacities. There is currently very little data on these cells in MS patients. The investigators therefore plan, in a second step, to characterize the phenotype of the different subpopulations of TFH at the periphery, but also in the CSF of MS patients.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laure Michel; Phone Number: +33 2 99 28 37 09; Email: laure.michel@chu-rennes.fr
• Study Contact Backup: Name: Emmanuelle Le Page; Phone Number: +33 2 99 28 37 09; Email: emmanuelle.le.page@chu-rennes.fr

Study Locations

• France
  • Rennes, France, 35033
    • Rennes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Regarding MS patients (remitting or progressive untreated):

• Adult (age greater than or equal to 18 years) of both sexes;
• MS fulfilling the criteria of McDonald 2017;
• Remittent or progressive form;
• No immunomodulatory or immunosuppressive therapy for at least 3 months;
• Free, informed and written consent signed by the patient.

Regarding Clinically Isolated Syndrome:

• Adult (age greater than or equal to 18 years) of both sexes;
• Clinically isolated syndrome suggestive of MS (at least two typical lesions in two different locations);
• Patient receiving a Lumbar Puncture (PL) for diagnostic purposes;
• No immunomodulatory or immunosuppressive therapy for at least 3 months;
• Free, informed and written consent signed by the patient.

Regarding non-MS patients with neurological inflammatory disease:

• Adult (age greater than or equal to 18 years) of both sexes;
• Patient with non-MS neurological inflammatory disease (examples: meningitis, neurolupus, neurosarcoidosis...);
• Patients with PL for diagnostic or surveillance purposes;
• No immunomodulatory or immunosuppressive therapy for at least 3 months;
• Free, informed and written consent signed by the patient.

Regarding healthy volunteers:

• Adult (age greater than or equal to 18 years) of both sexes;
• Free, informed and written consent signed by the volunteer.

Exclusion Criteria:

Regarding all patients:

• Pregnancy;
• Breastfeeding;
• Treatment with corticotherapy in the last month;
• Patient not affiliated to social security;
• Persons major subject to legal protection (safeguard of justice, guardianship, tutorship), persons deprived of their liberty.

Regarding healthy volunteers:

• Pregnancy;
• Breastfeeding;
• Not affiliated to social security;
• Persons major subject to legal protection (safeguard of justice, guardianship, tutorship), persons deprived of their liberty.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy volunteer; 45 subjects; A single visit	Other: Biological Samples; Venous sampling that is performed solely for the purpose of research. The total blood volume taken is 80 ml maximum (8 tubes of 10 ml).; Other: Biological Samples; Eight additional 10 ml tubes of blood and an additional 5 ml CSF tube will be taken from the patient during a sample taken for the patient's usual check-up /follow-up. Inpatients will also be offered stool removal.; Other: Biological Samples; The patient will be taken 8 additional tubes of 10 ml of blood (during a blood test performed for the usual assessment of the patient) and an additional 5 ml of CSF in a sample taken for the assessment of the patient.; Other: Biological Samples; Eight additional 10 ml tubes of blood will be taken from the patient during a sample taken for the patient's usual check-up / follow-up. Inpatients will also be offered stool removal
Other: Clinically Isolated Syndrome; • 35 subjects	Other: Biological Samples; Venous sampling that is performed solely for the purpose of research. The total blood volume taken is 80 ml maximum (8 tubes of 10 ml).; Other: Biological Samples; Eight additional 10 ml tubes of blood and an additional 5 ml CSF tube will be taken from the patient during a sample taken for the patient's usual check-up /follow-up. Inpatients will also be offered stool removal.; Other: Biological Samples; The patient will be taken 8 additional tubes of 10 ml of blood (during a blood test performed for the usual assessment of the patient) and an additional 5 ml of CSF in a sample taken for the assessment of the patient.; Other: Biological Samples; Eight additional 10 ml tubes of blood will be taken from the patient during a sample taken for the patient's usual check-up / follow-up. Inpatients will also be offered stool removal
Other: Non-MS patients with neurological inflammatory disease; • 30 subjects	Other: Biological Samples; Venous sampling that is performed solely for the purpose of research. The total blood volume taken is 80 ml maximum (8 tubes of 10 ml).; Other: Biological Samples; Eight additional 10 ml tubes of blood and an additional 5 ml CSF tube will be taken from the patient during a sample taken for the patient's usual check-up /follow-up. Inpatients will also be offered stool removal.; Other: Biological Samples; The patient will be taken 8 additional tubes of 10 ml of blood (during a blood test performed for the usual assessment of the patient) and an additional 5 ml of CSF in a sample taken for the assessment of the patient.; Other: Biological Samples; Eight additional 10 ml tubes of blood will be taken from the patient during a sample taken for the patient's usual check-up / follow-up. Inpatients will also be offered stool removal
Other: MS patients (remitting or progressive untreated); 30 untreated remittent patients; 30 progressive untreated patients	Other: Biological Samples; Venous sampling that is performed solely for the purpose of research. The total blood volume taken is 80 ml maximum (8 tubes of 10 ml).; Other: Biological Samples; Eight additional 10 ml tubes of blood and an additional 5 ml CSF tube will be taken from the patient during a sample taken for the patient's usual check-up /follow-up. Inpatients will also be offered stool removal.; Other: Biological Samples; The patient will be taken 8 additional tubes of 10 ml of blood (during a blood test performed for the usual assessment of the patient) and an additional 5 ml of CSF in a sample taken for the assessment of the patient.; Other: Biological Samples; Eight additional 10 ml tubes of blood will be taken from the patient during a sample taken for the patient's usual check-up / follow-up. Inpatients will also be offered stool removal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasmablasts frequency	Frequency of plasmablasts CD38hiCD27hi obtained after 6 days of differentiation of B cells in vitro, analyzed by flow cytometry	At Day 6 after differentiation of B cells

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Laure Michel, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Differentiation; B cells; Follicular helper T 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: 35RC18_8909_ABCD-SEP

Drug and device information, study documents

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