Clinical trial NCT03796611: Phenotypic and Functional Study of 4BL B Cells in Multiple Sclerosis (MS)
Official title: Phenotypic and Functional Study of 4BL B Cells in Multiple Sclerosis (MS)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis
Keywords: immunology
B cells
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2019-01-08
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: MS patients and controls: healthy controls and patients having non-MS neurological inflammatory disease and patients having other non inflammatory neurological disease.

Brief summary: 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: 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

Eligibility 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

Primary outcomes:
measure: the percentage of 4 BL cells in blood between MS patients and healthy controls
timeFrame: Baseline: one session
Secondary outcomes:
measure: the percentage of 4 BL cells in blood between MS patients and patients with inflammatory and non inflammatory neurological disease
timeFrame: Baseline: one session
measure: the percentage of 4 BL cells in CSF between MS patients and patients with inflammatory and non inflammatory neurological disease
timeFrame: Baseline: one session
measure: to analyse over time the evolution of 4BL percentages in blood in MS patients
timeFrame: 5 blood collection at baseline, 3, 6, 12, and 24 months after baseline
Other outcomes:
measure: biological bank with mononuclear cells from all the groups fo that study
timeFrame: through study completion, an average of 2 years
Locations:
Study officials:
affiliation: University Hospital, Lille
name: Hélène ZEPHIR, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: