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

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.

Study Overview

• Status: Terminated
• Conditions: Severe Sepsis; Inflammatory Response Syndrome, Systemic
• Intervention / Treatment: Biological: Residue of blood further to NFS; Biological: Bone marrow collected during myelogram routinely performed during hospitalization in ICU; Biological: Residue of blood further to preoperative workup; Biological: Bone marrow collected during a myelogram carried out for hematological pathology workup

• Study Type: Observational
• Enrollment (Actual): 68

Contacts and Locations

Study Locations

• France
  • Limoges, France, 87042
    • CHU de Limoges

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patient hospitalized in intensive care for sepsis evolving for less than 48 hours with two criteria of systemic inflammatory response syndrome

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; 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; Biological: Bone marrow collected during myelogram routinely performed during hospitalization in ICU
Control; 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; Biological: Bone marrow collected during a myelogram carried out for hematological pathology workup

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimate): September 16, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Sepsis; Myeloid-Derivated suppressive cell; Inflammatory Response Syndrome, Systemic
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease; Shock; Sepsis; Toxemia; Syndrome; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: I16019 (MDSC)