Clinical trial NCT05424627: Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus
Official title: Involvement of Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Systemic Lupus Erythematosus
Keywords: myeloid derived suppressor cells
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2022-06-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with active SLE

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.

Eligibility criteria: 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

Primary outcomes:
measure: MDSC percentage among total PBMC
timeFrame: Baseline
measure: MDSC percentage among total PBMC
timeFrame: 3 months
measure: MDSC percentage among total PBMC
timeFrame: 6 months
measure: MDSC percentage among total PBMC
timeFrame: Between 9 and 24 months if patient experience relapse during follow-up
Secondary outcomes:
measure: Serum cytokine levels
timeFrame: Baseline
measure: Serum cytokine levels
timeFrame: 3 months
measure: Serum cytokine levels
timeFrame: 6 months
measure: Serum cytokine levels
timeFrame: Between 9 and 24 months if patient experience relapse during follow-up
measure: MDSC inflammasome activation
timeFrame: Baseline
measure: MDSC inflammasome activation
timeFrame: 3 months
measure: MDSC inflammasome activation
timeFrame: 6 months
measure: MDSC inflammasome activation
timeFrame: Between 9 and 24 months if patient experience relapse during follow-up
measure: Immunometabolic profile
timeFrame: Baseline
measure: Immunometabolic profile
timeFrame: 3 months
measure: Immunometabolic profile
timeFrame: 6 months
measure: Immunometabolic profile
timeFrame: Between 9 and 24 months if patient experience relapse during follow-up
measure: MDSC subpopulations percentage
timeFrame: Baseline
measure: MDSC subpopulations percentage
timeFrame: 3 months
measure: MDSC subpopulations percentage
timeFrame: 6 months
measure: MDSC subpopulations percentage
timeFrame: Between 9 and 24 months if patient experience relapse during follow-up
Other outcomes:
Locations:
city: Vandoeuvre les nancy
country: France
facility: Thomas Moulinet
state: Lorraine
Study officials:
affiliation: CHRU de Nancy
name: Thomas Moulinet
role: PRINCIPAL_INVESTIGATOR
References: