Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04697407 |
| Other study ID # |
35RC20_9867_BREGS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 23, 2021 |
| Est. completion date |
May 23, 2023 |
Study information
| Verified date |
May 2023 |
| Source |
Rennes University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is
the leading cause of non-traumatic disability in young adults. Pathophysiopathologically, MS
has long been considered a disease mediated primarily by CD4+ T cells. However, recent
clinical trials demonstrating significant efficacy of B-lymphocyte (B-lymphocyte) depletive
therapies have highlighted the major role of this cell population in the development of MS.
Thus, it has been shown that these cells, in addition to their ability to secrete pathogenic
antibodies, produce pro-inflammatory cytokines in this disease, and an imbalance between
these potentially pathogenic pro-inflammatory B-Ls and regulatory ("anti-inflammatory") B-Ls
(Bregs) has been suggested.
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. Our team has thus
demonstrated that this cytokine, essentially produced by CD4+ T lymphocytes, triggers the
differentiation of naïve human B cells in vitro into plasma cells. And, more recently, the
analysis of the early response of BLs in mice disabled for the IL-2 receptor specifically in
mature BLs (Il2rbfl/flCD19cre/+) suggests a role of IL-2 in the acquisition of
suppressive/regulatory functions. In addition, 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 signaling induces the polarization and/or regulatory function of
Bregs in vivo and that deregulation of this 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.
The objective of this study is the analysis of the Bregs population in the blood of MS
patients (at the diagnostic stage and in different forms) who are untreated compared to
controls who are healthy in various aspects.
