Clinical trial NCT03744351: B Cell Differentiation in MS
Official title: Analysis of B Cell Differentiation in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Follicular helper T cells
B cells
Differentiation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2018-11-16
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Interventional study with minimal risks and constraints, prospective, monocentric.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasmablasts frequency
timeFrame: At Day 6 after differentiation of B cells
Secondary outcomes:
Other outcomes:
Locations:
city: Rennes
country: France
facility: Rennes University Hospital
Study officials:
affiliation: Rennes University Hospital
name: Laure Michel
role: PRINCIPAL_INVESTIGATOR
References: