Pediatric Immune Response to Multi-Organ Dysfunction

Not Applicable

Completed

• Conditions: Multiple Organ Dysfunction Syndrome
• Interventions: Biological: Blood test

• Registration Number: NCT04438460
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Multiple organ dysfunction (MOD) is defined by the association of at least two failures of vital organs, with various etiologies (septic shock, polytrauma, acute respiratory distress syndrome, etc.). Associated mortality remains high in children (between 20 and 50%).

In septic shock, one of the main causes of MOD, induced immunosuppression can occur, with immune alterations affecting all cells of immunity. This induced immunosuppression is associated with an additional risk of secondary acquired infections and death in adults. Among all the cells and all the markers studied, the expression of Human Leukocyte Antigen - DR isotype (HLA-DR) on the surface of the monocyte (mHLA-DR, expressed in number of sites per cell) appeared as one of the best biomarkers of this induced immunosuppression. Decreased expression of monocyte Human Leukocyte Antigen - DR isotype (mHLA-DR) in adults is linked to an increased risk of developing secondary infection and death.

These results were confirmed by team in the context of pediatric septic shock, with an attack of innate immunity in the foreground. Persistent lowering of mHLA-DR for more than 3 days after onset of shock was associated with the occurrence of secondary acquired infections: 50% of children had mHLA-DR of less than 8000 sites / cells on D3, of which 60 % developed secondary infection within 30 days. No child with mHLA-DR greater than 8000 sites / cells had secondary infection.

Such immune alterations appear to be non-specific for septic shock, as they have also been described after multiple trauma or severe respiratory infections.

The hypothesize is that multi-systemic aggression leading to multi-visceral failure syndrome could also lead to significant immunosuppression, regardless of the etiology of this MOD.

At present, the proportion of persistent immunosuppression induced by MOD, all etiologies combined, is poorly documented in pediatrics. Estimating this proportion in a large pediatric cohort, while exploring as fully as possible the associated immune alterations and acquired secondary infections, would improve the pathophysiological understanding and pediatric specificities of this phenomenon.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-28
• Study First Submitted QC: 2020-06-16
• Study First Posted: 2020-06-18
• Study Start: 2020-07-29
• Primary Completion: 2024-04-16
• Study Completion: 2024-04-16
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-27
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

Patient Group:

• 1 month < Age < 12 years
• Multiple organ dysfunction within 48 hours following intensive care unit admission
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority

Control Group:

• 1 month < Age < 12 years
• Hospitalized for simple elective surgery
• Beneficiary of a social security scheme.
• Consent signed by at least one parent / holder of parental authority

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Exclusion Criteria

Patient Group:

• Weight < 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment
• Hepatic cirrhosis
• Polymerase Chain Reaction (PCR) Severe acute respiratory syndrome coronavirus (SARS-CoV-2) positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
• Pediatric inflammatory multisystem syndrome (PIMS)

Control Group:

• Weight < 5 kg
• Known immunosuppression
• Prolonged corticotherapy
• Chronic inflammatory disease
• Malignant pathology with ongoing treatment
• Ongoing infection
• Organ failure
• Hepatic cirrhosis
• PCR SARS-CoV-2 positive or patient with Pediatric Inflammatory Multisystem Syndrome (PIMS)
• Pediatric inflammatory multisystem syndrome (PIMS)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Blood test	60 children aged 1 month to 12 years hospitalized for simple elective surgery will be included in this study
Patient group	Blood test	150 children aged 1 month to 12 years with multi-visceral failure syndrome within 48 hours of hospitalization in pediatric resuscitation will be included in this study

Primary Outcome Measures

Name	Time	Method
Secondary acquired infection (SAI)	Day 60	This criterion will be related to the duration of follow-up and expressed as an incidence of SAI occurrence.This incidence will be calculated in the two groups "Presence of immunosuppression" and "Absence of immunosuppression", defined from the value of mHLA-DR at D3-D5: "Presence of immunosuppression" if mHLA-DR \< 8000 sites/cells and "Absence of immunosuppression" if mHLA-DR ≥ 8000 sites/cells. The diagnosis of secondary acquired infection will be made by an independent committee.

Secondary Outcome Measures

Name	Time	Method
Monocytic and dendritic subpopulations measurement	Day 60	Characterization of monocytic and dendritic subpopulations will be realized
mHLA-DR expression : Characterization of alterations in the myeloid lineage	Day 60	mHLA-DR expressed as a number of site / cell will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Myeloid Derived Suppressor Cells (MDSC) measurement	Day 1	Characterization of MDSC will be measured and compared between patient and control
plasma cytokines : Characterization of alterations in the myeloid lineage	Day 60	Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
blood counts : Characterization of alterations in the myeloid lineage	Day 60	Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte	Day 1	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte. It will be compared between patient and control.
Intra-cellular production of TNFα by the monocyte	Day 3	Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.
Gamma-delta T lymphocytes measurement	Day 60	Characterization of gamma-delta T lymphocytes will be realized
transcriptome : Characterization of alterations in the myeloid lineage	Day 60	Gene expression through messenger ribonucleic acid (mRNA) analysis will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
mHLA-DR measurement	Day 60	Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.
MDSC measurement	Day 3	Characterization of MDSC will be measured

Trial Locations

Locations (2)

Hopital Mère Enfant; 🇫🇷 Nantes, France

Hôpital Femme Mère Enfant; 🇫🇷 Bron, France