Ignite Creation Date:
2024-05-06 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 1:53 PM
Study NCT ID:
NCT04697407
Status:
COMPLETED
Last Update Posted:
2023-05-24
First Post:
2021-01-04
Brief Title:
IL-2 Signaling and Polarization of Regulatory LBs Involvement in Multiple Sclerosis
Sponsor:
Rennes University Hospital
Organization:
Rennes University Hospital
Study Overview
Official Title:
BREGS - IL-2 Signaling and Polarization of Regulatory LBs Involvement in Multiple Sclerosis
Status:
COMPLETED
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BREGS
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-2IL2R signaling pathway in the pathogenesis of autoimmune diseases
The hypothesis is that IL-2IL2R 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 hypothesis is that IL-2IL2R 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
Detailed 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 Il2rbflflCD19cre suggests a role of IL-2 in the acquisition of suppressiveregulatory functions In addition numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2IL2R signaling pathway in the pathogenesis of autoimmune diseases
The hypothesis is that IL-2 signaling induces the polarization andor regulatory function of Bregs in vivo and that deregulation of this IL-2IL2R 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
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 Il2rbflflCD19cre suggests a role of IL-2 in the acquisition of suppressiveregulatory functions In addition numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2IL2R signaling pathway in the pathogenesis of autoimmune diseases
The hypothesis is that IL-2 signaling induces the polarization andor regulatory function of Bregs in vivo and that deregulation of this IL-2IL2R 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None