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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
186
For patient group, blood tests will be performed at day 1-2, day 3-5 and day 60. For control group, blood test will be performed the day of elective surgery.
Hôpital Femme Mère Enfant
Bron, France
Hopital Mère Enfant
Nantes, France
Secondary acquired infection (SAI)
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.
Time frame: Day 60
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time frame: Day 1
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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
Time frame: Day 1
transcriptome : Characterization of alterations in the myeloid lineage
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.
Time frame: Day 1
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time frame: Day 1
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months
Time frame: Day 3
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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.
Time frame: Day 3
transcriptome : Characterization of alterations in the myeloid lineage
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.
Time frame: Day 3
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time frame: Day 3
blood counts : Characterization of alterations in the myeloid lineage
Blood cell counts will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time frame: Day 60
mHLA-DR expression : Characterization of alterations in the myeloid lineage
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.
Time frame: Day 60
transcriptome : Characterization of alterations in the myeloid lineage
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.
Time frame: Day 60
plasma cytokines : Characterization of alterations in the myeloid lineage
Cytokine levels will be compared between the groups "secondary acquired infections" and "no secondary acquired infection" occurring within 2 months.
Time frame: Day 60
mHLA-DR measurement
Evaluation of the immunological recovery at month 2 with regard to the initial state and in comparison with the controls.
Time frame: Day 60
Myeloid Derived Suppressor Cells (MDSC) measurement
Characterization of MDSC will be measured and compared between patient and control
Time frame: Day 1
Intra-cellular production of tumor necrosis factor alpha (TNFα) by the monocyte
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.
Time frame: Day 1
MDSC measurement
Characterization of MDSC will be measured
Time frame: Day 3
Intra-cellular production of TNFα by the monocyte
Evaluate the feasibility of a new test : measure of the intra-cellular production of TNF α by the monocyte.
Time frame: Day 3
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control.
Time frame: Day 1
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control.
Time frame: Day 1
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Time frame: Day 3
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized
Time frame: Day 3
Monocytic and dendritic subpopulations measurement
Characterization of monocytic and dendritic subpopulations will be realized
Time frame: Day 60
Gamma-delta T lymphocytes measurement
Characterization of gamma-delta T lymphocytes will be realized
Time frame: Day 60
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