Systemic Lupus Erythematosus
Conditions
Keywords
myeloid derived suppressor cells
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.
Interventions
None listed
Sponsors
Central Hospital, Nancy, France
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MDSC percentage among total PBMC | Baseline | Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum cytokine levels | Baseline | pro and anti-inflammatory cytokine levels in serum |
| MDSC inflammasome activation | Baseline | flow cytometry assessment of inflammasome activation within MDSCs |
| Immunometabolic profile | Baseline | flow cytometry assessment of metabolic profile of MDSCs |
| MDSC subpopulations percentage | Baseline | flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC |
Countries
France
Contacts
Primary ContactThomas Moulinet, MD
Outcome results
None listed