Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

— MDSC-SLE  

Official title:

Involvement of Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05424627
• Other study ID #: 2022-A00601-42
• Status: Not yet recruiting
• Start date: July 15, 2022
• Est. completion date: January 15, 2027

Study information

• Verified date: June 2022
• Source: Central Hospital, Nancy, France
• Contact: Thomas Moulinet, MD
• Phone: +33383155304
• Email: t.moulinet[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: January 15, 2027
• Est. primary completion date: July 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Locations

Country	Name	City	State
France	Thomas Moulinet	Vandoeuvre les nancy	Lorraine

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MDSC percentage among total PBMC	Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score)	Baseline
Primary	MDSC percentage among total PBMC	Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score)	3 months
Primary	MDSC percentage among total PBMC	Correlation between MDSC percentage among total PBMC and Clinical activity of SLE (SLEDAI score)	6 months
Primary	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	Serum cytokine levels	pro and anti-inflammatory cytokine levels in serum	Baseline
Secondary	Serum cytokine levels	pro and anti-inflammatory cytokine levels in serum	3 months
Secondary	Serum cytokine levels	pro and anti-inflammatory cytokine levels in serum	6 months
Secondary	Serum cytokine levels	pro and anti-inflammatory cytokine levels in serum	Between 9 and 24 months if patient experience relapse during follow-up
Secondary	MDSC inflammasome activation	flow cytometry assessment of inflammasome activation within MDSCs	Baseline
Secondary	MDSC inflammasome activation	flow cytometry assessment of inflammasome activation within MDSCs	3 months
Secondary	MDSC inflammasome activation	flow cytometry assessment of inflammasome activation within MDSCs	6 months
Secondary	MDSC inflammasome activation	flow cytometry assessment of inflammasome activation within MDSCs	Between 9 and 24 months if patient experience relapse during follow-up
Secondary	Immunometabolic profile	flow cytometry assessment of metabolic profile of MDSCs	Baseline
Secondary	Immunometabolic profile	flow cytometry assessment of metabolic profile of MDSCs	3 months
Secondary	Immunometabolic profile	flow cytometry assessment of metabolic profile of MDSCs	6 months
Secondary	Immunometabolic profile	flow cytometry assessment of metabolic profile of MDSCs	Between 9 and 24 months if patient experience relapse during follow-up
Secondary	MDSC subpopulations percentage	flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC	Baseline
Secondary	MDSC subpopulations percentage	flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC	3 months
Secondary	MDSC subpopulations percentage	flow cytometry assessment of known (Monocytic, Granulocytic, Early-stage) and unknow subpopulations of MDSC	6 months
Secondary	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