Clinical trial NCT04438460: Pediatric Immune Response to Multi-Organ Dysfunction
Official title: Pediatric Immune Response to Multi-Organ Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Organ Dysfunction Syndrome
Keywords: Multiple organ dysfunction
Immunosuppression
mHLA-DR
Pediatrics
Secondary infection
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2020-06-18
Enrollment: 186
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

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)

Primary outcomes:
measure: Secondary acquired infection (SAI)
timeFrame: Day 60
Secondary outcomes:
measure: blood counts : Characterization of alterations in the myeloid lineage
timeFrame: Day 1
measure: mHLA-DR expression : Characterization of alterations in the myeloid lineage
timeFrame: Day 1
measure: transcriptome : Characterization of alterations in the myeloid lineage
timeFrame: Day 1
measure: plasma cytokines : Characterization of alterations in the myeloid lineage
timeFrame: Day 1
measure: blood counts : Characterization of alterations in the myeloid lineage
timeFrame: Day 3
measure: mHLA-DR expression : Characterization of alterations in the myeloid lineage
timeFrame: Day 3
measure: transcriptome : Characterization of alterations in the myeloid lineage
timeFrame: Day 3
measure: plasma cytokines : Characterization of alterations in the myeloid lineage
timeFrame: Day 3
measure: blood counts : Characterization of alterations in the myeloid lineage
timeFrame: Day 60
measure: mHLA-DR expression : Characterization of alterations in the myeloid lineage
timeFrame: Day 60
measure: transcriptome : Characterization of alterations in the myeloid lineage
timeFrame: Day 60
measure: plasma cytokines : Characterization of alterations in the myeloid lineage
timeFrame: Day 60
measure: mHLA-DR measurement
timeFrame: Day 60
measure: Myeloid Derived Suppressor Cells (MDSC) measurement
timeFrame: Day 1
measure: Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte
timeFrame: Day 1
measure: MDSC measurement
timeFrame: Day 3
measure: Intra-cellular production of TNFα by the monocyte
timeFrame: Day 3
measure: Monocytic and dendritic subpopulations measurement
timeFrame: Day 1
measure: Gamma-delta T lymphocytes measurement
timeFrame: Day 1
measure: Monocytic and dendritic subpopulations measurement
timeFrame: Day 3
measure: Gamma-delta T lymphocytes measurement
timeFrame: Day 3
measure: Monocytic and dendritic subpopulations measurement
timeFrame: Day 60
measure: Gamma-delta T lymphocytes measurement
timeFrame: Day 60
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Nantes
country: France
facility: Hopital Mère Enfant
Study officials:
References: