Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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
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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.

Official Title
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Involvement of Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDSC percentage among total PBMC | Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score) | Baseline | 
| MDSC percentage among total PBMC | Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score) | 3 months | 
| MDSC percentage among total PBMC | Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score) | 6 months | 
| MDSC percentage among total PBMC | Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score) | Between 9 and 24 months if patient experience relapse during follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokine levels | pro and anti-inflammatory cytokine levels in serum | Baseline | 
| Serum cytokine levels | pro and anti-inflammatory cytokine levels in serum | 3 months | 
| Serum cytokine levels | pro and anti-inflammatory cytokine levels in serum | 6 months | 
| Serum cytokine levels | pro and anti-inflammatory cytokine levels in serum | Between 9 and 24 months if patient experience relapse during follow-up | 
| MDSC inflammasome activation | flow cytometry assessment of inflammasome activation within MDSCs | Baseline | 
| MDSC inflammasome activation | flow cytometry assessment of inflammasome activation within MDSCs | 3 months | 
| MDSC inflammasome activation | flow cytometry assessment of inflammasome activation within MDSCs | 6 months | 
| MDSC inflammasome activation | flow cytometry assessment of inflammasome activation within MDSCs | Between 9 and 24 months if patient experience relapse during follow-up | 
| Immunometabolic profile | flow cytometry assessment of metabolic profile of MDSCs | Baseline | 
| Immunometabolic profile | flow cytometry assessment of metabolic profile of MDSCs | 3 months | 
| Immunometabolic profile | flow cytometry assessment of metabolic profile of MDSCs | 6 months | 
| Immunometabolic profile | flow cytometry assessment of metabolic profile of MDSCs | Between 9 and 24 months if patient experience relapse during follow-up | 
| MDSC subpopulations percentage | flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC | Baseline | 
| MDSC subpopulations percentage | flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC | 3 months | 
| MDSC subpopulations percentage | flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC | 6 months | 
| MDSC subpopulations percentage | flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC | Between 9 and 24 months if patient experience relapse during follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myeloid derived suppressor cells