Multiple Organ Dysfunction Syndrome
Conditions
Keywords
Multiple organ dysfunction, Immunosuppression, mHLA-DR, Pediatrics, Secondary infection
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.
Interventions
BIOLOGICALBlood test
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.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 12 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| mHLA-DR expression : Characterization of alterations in the myeloid lineage | Day 1 | 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 |
| transcriptome : Characterization of alterations in the myeloid lineage | Day 1 | 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. |
| plasma cytokines : Characterization of alterations in the myeloid lineage | Day 1 | Cytokine levels 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. |
| Myeloid Derived Suppressor Cells (MDSC) measurement | Day 1 | Characterization of MDSC will be measured and compared between patient and control |
| blood counts : Characterization of alterations in the myeloid lineage | Day 1 | Blood cell counts will be compared between the groups secondary acquired infections and no secondary acquired infection occurring within 2 months. |
| MDSC measurement | Day 3 | Characterization of MDSC will be measured |
| 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. |
| Monocytic and dendritic subpopulations measurement | Day 1 | Characterization of monocytic and dendritic subpopulations will be realized and compared between patient and control. |
| Gamma-delta T lymphocytes measurement | Day 1 | Characterization of gamma-delta T lymphocytes will be realized and compared between patient and control. |
| 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. |
Countries
France
Outcome results
None listed