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MDSC-SLE: Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus

Sponsor
Central Hospital, Nancy, France (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05424627
Collaborator
(none)
80
Enrollment
1
Location
54
Anticipated Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

    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.

    Study Design

    Study Type:
    Observational [Patient Registry]
    Anticipated Enrollment :
    80 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Involvement of Myeloid Derived Suppressor Cells in Systemic Lupus Erythematosus
    Anticipated Study Start Date :
    Jul 15, 2022
    Anticipated Primary Completion Date :
    Jul 15, 2026
    Anticipated Study Completion Date :
    Jan 15, 2027

    Outcome Measures

    Primary Outcome Measures

    1. MDSC percentage among total PBMC [Baseline]

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

    2. MDSC percentage among total PBMC [3 months]

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

    3. MDSC percentage among total PBMC [6 months]

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

    4. MDSC percentage among total PBMC [Between 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

    1. Serum cytokine levels [Baseline]

      pro and anti-inflammatory cytokine levels in serum

    2. Serum cytokine levels [3 months]

      pro and anti-inflammatory cytokine levels in serum

    3. Serum cytokine levels [6 months]

      pro and anti-inflammatory cytokine levels in serum

    4. Serum cytokine levels [Between 9 and 24 months if patient experience relapse during follow-up]

      pro and anti-inflammatory cytokine levels in serum

    5. MDSC inflammasome activation [Baseline]

      flow cytometry assessment of inflammasome activation within MDSCs

    6. MDSC inflammasome activation [3 months]

      flow cytometry assessment of inflammasome activation within MDSCs

    7. MDSC inflammasome activation [6 months]

      flow cytometry assessment of inflammasome activation within MDSCs

    8. MDSC inflammasome activation [Between 9 and 24 months if patient experience relapse during follow-up]

      flow cytometry assessment of inflammasome activation within MDSCs

    9. Immunometabolic profile [Baseline]

      flow cytometry assessment of metabolic profile of MDSCs

    10. Immunometabolic profile [3 months]

      flow cytometry assessment of metabolic profile of MDSCs

    11. Immunometabolic profile [6 months]

      flow cytometry assessment of metabolic profile of MDSCs

    12. Immunometabolic profile [Between 9 and 24 months if patient experience relapse during follow-up]

      flow cytometry assessment of metabolic profile of MDSCs

    13. MDSC subpopulations percentage [Baseline]

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

    14. MDSC subpopulations percentage [3 months]

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

    15. MDSC subpopulations percentage [6 months]

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

    16. MDSC subpopulations percentage [Between 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Thomas Moulinet Vandoeuvre les nancy Lorraine France 54500

    Sponsors and Collaborators

    • Central Hospital, Nancy, France

    Investigators

    • Principal Investigator: Thomas Moulinet, CHRU de Nancy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Thomas MOULINET, MD, Central Hospital, Nancy, France
    ClinicalTrials.gov Identifier:
    NCT05424627
    Other Study ID Numbers:
    • 2022-A00601-42
    First Posted:
    Jun 21, 2022
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Thomas MOULINET, MD, Central Hospital, Nancy, France
    myeloid derived suppressor cells
    Additional relevant MeSH terms:
    Lupus Erythematosus, Systemic

    Study Results

    No Results Posted as of Jun 21, 2022