B Cell Differentiation in MS

Study Overview
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Brief Summary
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Interventional study with minimal risks and constraints, prospective, monocentric.

Detailed Description
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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.

Official Title
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Analysis of B Cell Differentiation in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Biological Samples
* Other: Biological Samples
* Other: Biological Samples
* Other: Biological Samples


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy volunteer<br>45 subjects A single visit | Other: Biological Samples<br>* 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).<br>|
| Other: Clinically Isolated Syndrome<br>• 35 subjects | Other: Biological Samples<br>* 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.<br>|
| Other: Non-MS patients with neurological inflammatory disease<br>• 30 subjects | Other: Biological Samples<br>* 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.<br>|
| Other: MS patients (remitting or progressive untreated)<br>30 untreated remittent patients 30 progressive untreated patients | Other: Biological Samples<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicular helper T cells, B cells, Differentiation