IL-2 Signaling and Polarization of Regulatory LBs: Involvement in Multiple Sclerosis

NCT04697407 | Completed

• 1 other identifier: 35RC20_9867_BREGS
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte depletive therapies have highlighted the major role of this cell population in the development of MS. Among B-Ls, regulatory ("anti-inflammatory") B-Ls (Bregs) have protective functions in autoimmune diseases including MS, however the mechanisms that regulate the development and function of Bregs are poorly characterized. In our research laboratory (INSERM UMR1236), one of the lines of research focuses on the role of interleukin-2 (IL-2) signaling in the fate of the B lymphocyte. Numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2/IL2R signaling pathway in the pathogenesis of autoimmune diseases. The hypothesis is that IL-2/IL2R pathway could contribute, by a mechanism intrinsic to B lymphocytes, to the development of autoimmune diseases such as MS. While a defect in IL-2 signaling plays a critical role in the pathogenesis of MS, the impact of this defective signaling on regulatory B lymphocyte populations, which has been shown to play a protective role in the development of the disease, has never been studied. This study could help establish a new mechanism predisposing patients to develop the disease.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Frequency of Bregs in blood of MS patients

  Comparison of the frequency of Bregs in the blood of untreated MS patients (at the diagnostic stage and in different forms of MS: Relapsing-remitting (RR), Primary Progressive (PP) and Secondary Progressive (SP)) compared to healthy controls matched for age and gender.

  1 month

Secondary Outcomes (3)

• Frequency of Bregs in the CSF of MS patients

  1 month

• Comparison of IL-2, soluble IL2RA, IL-10, IL-21 and IL-5 protein concentrations

  1 month

• Comparison of the concentrations in Igs

  1 month

Study Arms (3)

MS Patients

EXPERIMENTAL

Patients with MS at any stage and for any type of MS : MS at the onset of the disease, Clinically isolated syndrome (CIS), Relapsing-remitting MS (RRMS), Primary progressive MS (PPMS), Secondary progressive MS (SPMS)

Biological: Blood sampling; Biological: CSF sampling

non MS Patients

ACTIVE COMPARATOR

Patients with a neurological and immunological disease except MS.

Biological: Blood sampling; Biological: CSF sampling

Healthy volunteers

ACTIVE COMPARATOR

Biological: Blood sampling

Interventions

Blood sampling BIOLOGICAL

In all groups, 80 ml of blood will be collected. For patients, this will be done during routine cares.

Healthy volunteers; MS Patients; non MS Patients

CSF sampling BIOLOGICAL

Only in both patients groups whom will have a CSF sampling in routine care, some CSF will be collected for the study in addition, with a limit of 5 ml for routine care and study.

MS Patients; non MS Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients at the onset of illness :
• With a strong suspicion of MS requiring an LP to confirm the diagnosis (suggestive neurological symptoms AND more than two typical lesions on MRI) ; OR
• MS patients (untreated RR, SP or PP) :
• With MS that meets the MacDonald 2017 criteria;
• With relapsing-remitting (RR), secondary-progressive (SP) or primary-progressive (PP) MS; OR
• Non-MS patients :
• Presenting a non MS neurological inflammatory disease (meningitis, neurolupus, neurosarcoidosis, autoimmune encephalitis, acute polyradiculoneuritis);
• Benefiting from an LP for diagnostic or monitoring purposes;
• AND
• At least 18 years old;
• Without immunomodulating or immunosuppressive background treatment for at least 3 months;
• Without systemic corticosteroid treatment for at least 3 months;
• Having signed a free, informed and written consent.
• Affiliated with a social security system
• At least 18 years old;

You may not qualify if:

• For all groups
• Pregnancy ;
• Breastfeeding ;
• Persons of full age subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.
• Healthy volunteers :
• Absence of autoimmune pathologies
• Without immunomodulating or immunosuppressive background treatment for at least 3 months;
• Without systemic corticosteroid treatment for at least 3 months.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

CHU Rennes

Rennes, France

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Laure Michel, Md

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: March 23, 2021
• Primary Completion: May 23, 2023
• Study Completion: May 23, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)