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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunology, B cells