Plasma Levels of Danger-Associated Molecular Patterns in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED2)

Plasma Levels of Danger-Associated Molecular Patterns (DAMPs) in Young Children After Cardiac Surgery Under Cardiopulmonary Bypass (IMMUNOPED 2)

The investigators have previously reported that cardiac surgery with CPB ( cardiopulmonary bypass) in young infants induced a drastic reduction in mHLA-DR ( Human Leucocyte Antigen) expression, which represents one of innate immune mediator. Danger-Associated Molecular Patterns (DAMPs) can elicit immune response and may subsequentely induce an immune-suppressed state. The investigators hypothesize that CPB causes excessive DAMP release, leading to the development of immune suppression. Thus, DAMPs release will be assessed in patients undergoing CBP, and consequences on immune suppression will be evaluated.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgical Procedure
• Intervention / Treatment: Diagnostic test: Blood drop sampling

Detailed Description

Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 will be measured at four time points (prior to the onset of CPB, Hour 6 postoperative, day 1 and day 3 after surgery). HLA-DR gene expression will be determined before surgery and at day 3 postoperative. The direct effect of DAMPs release and immune suppression will be assessed by in vitro experiments.

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to pediatric resuscitation at the Nantes University Hospital after cardiac surgery under CEC ( extra-corporal circulation) and aged less than 3 months meeting the criteria for inclusion and non-inclusion of the study will be included. We can objectify the recruitment of 80 patients in total over 3 years.

Since natural evolution (variation of rates and their kinetics) of the secretion of different DAMPs during the first months of life is unknown, the investigators added a control group to know the expression and kinetics of DAMPs outside cardiac surgery under CEC. This control group will be defined by infants under 3 months of age undergoing heavy digestive surgery and having a central venous catheter to facilitate access to blood samples (n = 20).

Description

Inclusion Criteria:

• Patient admitted to pediatric intensive care at Nantes University Hospital after cardiac surgery with bypass graft
• Age ≤ 3 months corrected age. Control group: patients less than 3 months old following cardiac surgery without CEC or digestive surgery with a central venous catheter.

Exclusion Criteria:

• Futility of care with cessation of blood tests as part of a limitation of active therapies;
• Absence of parents for information
• Refusal of parents after information (Lack of parental consent)
• Blood volume collected for medical purposes incompatible with the needs of the research

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study population; The study population must correspond to the research inclusion criteria: Patient admitted to pediatric intensive care at Nantes University Hospital after cardiac surgery on bypass grafts	Diagnostic test: Blood drop sampling; For each patient included, 1 additional EDTA blood tube (2 ml) will be collected for research purposes at different times (4 visits), and 1 PAXgene-type tube adapted for pediatric collection of only 500 μl (2 visits).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.	Change of plasma levels of DAMPs after cardiopulmonary bypass Plasma levels of heat shock protein (HSP 70), high mobility group box (HMGB1), S100A9 and IL-33 before and after CBP.	prior to the onset of CPB, 6 hours, day 1 and day 3 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of DAMPs on immune function:In vitro change of HLA-DR expression.	In vitro change of HLA-DR expression induced by plasma containing different concentrations of DAMPs.	6 hours after surgery
Effect of DAMPs on immune function:Secretion of IL-10 ( Interleukine 10).	Secretion of IL-10 by different immune cells induced by plasma containing different concentrations of DAMPs.	6 hours after surgery

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Alexis Chenouard, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): December 2, 2025

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: June 7, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppression; infant; cardiopulmonary bypass; immunosuppression; infant
• Other Study ID Numbers: RC19_0402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No