MUltiple Sclerosis : T Cell / B Cell Exploration

Study Overview
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Brief Summary
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This study, an ancillary to ABCD-SEP (NCT03744351), will be interested in more precisely characterizing circulating and infiltrating TH cells in Multiple Sclerosis whether at the transcriptomic level or at the functional level.

Detailed Description
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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) affecting mostly young adults between 20 and 40 years of age. This disease is the leading cause of non-traumatic disability in young adults. MS has long been considered a predominantly T-cell mediated disease. However, the remarkable efficacy of anti-CD20 monoclonal antibodies in this disease has demonstrated the major role of B-cell in the pathophysiology of this disease. The B-cell have many functions: these cells are indeed able to secrete cytokines (pro and anti inflammatory), to present antigens to T lymphocytes, but also to differentiate into plasmocytic cells and thus to secrete immunoglobulins. Several studies have shown that B-cell in patients with MS secrete significantly more pro-inflammatory cytokines (GM-CSF, IL-6, TNFα). In addition, infiltrates and tertiary lymphoid structures have been found in the meninges of patients with MS, particularly in progressive forms of the disease. It seems clear to this day that these cells are strongly involved in the development of MS. Despite the many advances made recently in understanding the role of B-cell in the pathophysiology of MS, the precise involvement of plasma cells and their functions at different stages of the disease remains unclear. Folluclar helper T cells (TFH) play a crucial role in lymphocyte B differentiation. These cells are located within the germinal centers in the secondary lymphoid organs, and their memory compartment also circulates in the blood. Several circulating TFH subpopulations have recently been defined, with different helping capacities. This study, an ancillary to ABCD-SEP (NCT03744351), will be interested in more precisely characterizing circulating and infiltrating TH cells in Multiple Sclerosis whether at the transcriptomic level or at the functional level.

Official Title
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T Cell/B Cell Collaboration in Multiple Sclerosis: Exploring an Intimate Relationship

Conditions
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Multiple Sclerosis

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 health insurance; 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the transcriptome profile of infiltrating TFH cells from CIS patients to non-MS patients with neurological inflammatory diseases | Comparison of each gene expression of infiltrating TFH cells from CIS patients to those of non-MS patients with neurological inflammatory diseases by RNAsequencing | At inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the transcriptome profile of infiltrating TFH cells from CIS patients to healthy volunteers. | Comparison of each gene expression of infiltrating TFH cells from CIS patients to those of healthy volunteers (HV) by RNAsequencing | At inclusion | 
| To compare the B cell differentiation helping abilities of TFH cells from MS patients to those of HV | Analysis of B cell phenotype after 7 days of in vitro coculture assays and comparison of the frequencies between MS patients and HV | At inclusion | 
| To compare the migration abilities of TFH cells from MS patients to those of HV | Analysis of the rate, number and phenotype of migrating TFH cells after 12 to 24 hours using an in vitro model of Blood Brain Barrier in MS patients compared to HV | At inclusion |