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

University Hospital, Lille

Status: Unknown

Conditions: Multiple Sclerosis

Study type: Observational

Funder types: Other

Identifiers

NCT03796611

2016_04

2017-A00835-48 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 172 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

172 participants in 4 patient groups

multiple sclerosis patient

Description:

MS is defined according to McDonald criteria 2017. MS patients included have a disease duration of less than 1 year

other neurological inflammatory disease

Description:

autoimmune encephalitis, myasthenia gravis, chronic inflammatory demyelinating polyradiculitis

neurological non inflammatory disease

Description:

benign intracranial hypertension, degenerative disorder

healthy controls

Description:

transfusion volunteers from transfusion center