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Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Not yet recruiting
Conditions
Systemic Lupus Erythematosus
Registration Number
NCT05424627
Lead Sponsor
Central Hospital, Nancy, France
Brief Summary

Systemic Lupus Erythematosus (SLE) is a chronic invalidating chronic condition, with potential articular, cutaneous, renal, and neurologic involvement. Its pathophysiology is complex, and involves genetic, environmental and hormonal factors, leading to tolerance rupture. Among regulatory cells, Myeloid Derived Suppressor Cells (MDSCs) have been described as being increased during SLE, furthermore during flares. MDSCs are defined phenotypically as being HLA-DR-CD3-CD19-CD33+CD11b+, and either CD14+ (Monocytic MDSCs), CD15+ (Granulocytic MDSCs), or CD14-CD15- (Early-stage MDSCs). However, data regarding their immunosuppressive properties are conflicting, some studies identifying regulatory properties, while other have demonstrated a pro-inflammatory involvement through the induction of Th17 lymphocytes.

The objectives of this study is to assess the involvement of MDSC in SLE through accurate phenotypical and functional assessment, as well as characterizing their immunometabolic profile, and to identify innovative therapeutic strategies.

Detailed Description

Systemic Lupus Erythematosus (SLE) is a chronic invalidating chronic condition, with potential articular, cutaneous, renal, and neurologic involvement. Its pathophysiology is complex, and involves genetic, environmental and hormonal factors, leading to tolerance rupture. Among regulatory cells, Myeloid Derived Suppressor Cells (MDSCs) have been described as being increased during SLE, furthermore during flares. MDSCs are defined phenotypically as being HLA-DR-CD3-CD19-CD33+CD11b+, and either CD14+ (Monocytic MDSCs), CD15+ (Granulocytic MDSCs), or CD14-CD15- (Early-stage MDSCs). However, data regarding their immunosuppressive properties are conflicting, some studies identifying regulatory properties, while other have demonstrated a pro-inflammatory involvement through the induction of Th17 lymphocytes.

To gain insight into the involvement of MDSC in SLE, both deep phenotypical characterization of MDSC and functional assessment will be performed, as well as immunometabolic characterization. This data will be correlated to the clinical presentation and activity of SLE.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Active systemic lupus erythematosus (SLEDAI > or = 1)
  • Written informed consent
Exclusion Criteria
  • Chronic or acute infection
  • Other active auto-immune condition
  • Active cancer
  • Age below 18

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
MDSC percentage among total PBMCBetween 9 and 24 months if patient experience relapse during follow-up

Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score)

Secondary Outcome Measures
NameTimeMethod
MDSC inflammasome activationBetween 9 and 24 months if patient experience relapse during follow-up

flow cytometry assessment of inflammasome activation within MDSCs

MDSC subpopulations percentageBetween 9 and 24 months if patient experience relapse during follow-up

flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC

Immunometabolic profileBetween 9 and 24 months if patient experience relapse during follow-up

flow cytometry assessment of metabolic profile of MDSCs

Serum cytokine levelsBetween 9 and 24 months if patient experience relapse during follow-up

pro and anti-inflammatory cytokine levels in serum

Trial Locations

Locations (1)

Thomas Moulinet

🇫🇷

Vandoeuvre les nancy, Lorraine, France

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