Following of Myeloid-derived Suppressor Cells (MDSC) in Severe Sepsis: What Relationship With Systemic Inflammatory Syndrome?

Study Overview
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Brief Summary
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Sepsis remains a major cause of death in developed countries. A better understanding of the mechanisms involved in the regulation of inflammatory and immune response of patients with severe sepsis is an important step that could open the way for new therapeutic approaches.

Official Title
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Following of Myeloid-derived Suppressor Cells (MDSC) in Severe Sepsis: What Relationship With Systemic Inflammatory Syndrome?

Conditions
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Severe Sepsis, Inflammatory Response Syndrome, Systemic

Intervention / Treatment
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* Biological: Residue of blood further to NFS
* Biological: Residue of blood further to preoperative workup
* Biological: Bone marrow collected during a myelogram carried out for hematological pathology workup
* Biological: Bone marrow collected during myelogram routinely performed during hospitalization in ICU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥18 years old Patient with two criteria of systemic inflammatory response syndrome and one of the four following criteria within 24 hours of hospitalization in ICU: Lactate >4 mmol/L PaO2 / FiO2 <200 in the presence of lung disease as infectious source Vasopressor: adrenaline or noradrenaline ≥0.25 µg/kg/min for at least 6 hours to maintain a systolic blood pressure ≥90 mmHg or mean arterial pressure ≥65 mmHg Thrombocytopenia linked to sepsis with platelet count <100,000 / ml or a decrease ≤50% within 48 hours Exclusion Criteria: Pregnancy progressive solid cancer HIV infection History of blood or inflammatory disease long-term immunosuppressive treatment Prior episode of Sepsis in the previous month Chronic Dialysis Patient Patient under guardianship Patient not affiliated with a social security system

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>Patient hospitalized in intensive care for sepsis evolving for less than 48 hours with two criteria of systemic inflammatory response syndrome | Biological: Residue of blood further to NFS<br> <br> Biological: Bone marrow collected during myelogram routinely performed during hospitalization in ICU<br> <br> |
| Control<br>10 Patients hospitalized for a hematologic pathology workup considered normal by two haematologists and 10 patients hospitalized for a preoperative workup. | Biological: Residue of blood further to preoperative workup<br> <br> Biological: Bone marrow collected during a myelogram carried out for hematological pathology workup<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peripheral Blood MDSC concentration during ICU hospitalization for Severe Sepsis | Number of patients showing an increase of Myeloid derived suppressive cells from baseline at Day 30. Kinetic of Myeloid derived suppressive cells through weekly measures of Absolute Cell Counts (using flow cytometry) | Average 30 days - Patients will be followed up until hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immuno- inflammatory status | Pro-inflammatory cytokines determined by flow cytometry | Day 0, Day3, Day 7 and once a week until the intensive care unit discharge | 
| MDSCs presence in the blood and bone marrow. | Concentration of MDSC in the blood determined by flow cytometry | Day 0 | 
| Assessment of MDSC specific gene expressions | Measurement of MDSC activation by real-time qRT-PCRMDSC cell culture | Day 0 vs Days 3, 7, 14, 21, 28 | 
| Assessment of MDSC functional status | Inhibition of T cell proliferation capacity (co-culture assay in vitro)MDSC cell culture | Day 0 vs Days 3, 7, 14, 21, 28 | 
| Mortality | Dead or alive | Day 28 and Day 90 | 
| Incidence of hospital acquired secondary infections at Day 28 | Incidence of hospital acquired secondary infections at Day 28 | Day 28 | 
| SOFA score | Calculating of SOFA score | Day 0, Day3, Day 7 and once a week until the intensive care unit discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloid-Derivated suppressive cell, Sepsis, Inflammatory Response Syndrome, Systemic