1056: Precision Medicine Immune Profiling of Pediatric Patients with Multiple Organ Dysfunction Syndrome.

Document Type

Conference Proceeding

Publication Date

2025

Publication Title

Critical care medicine

Abstract

Introduction: Multiple organ dysfunction syndrome (MODS) accounts for 11-80% of admissions and is associated with high morbidity and mortality in the pediatric intensive care unit (PICU). Classified as the failure of more than one organ, MODS, transitions from sepsis to a more severe state through immune dysregulation. This immune response is varied, with responses ranging from macrophage activation syndrome to immunoparalysis. The integration of clinical data with immune profiling could provide vital understanding of the disease process within and between each MODS patient. We hypothesize that the diverse etiologies of MODS will lead to unique immunophenotypes predictive of their disease course.

Methods: After IRB approval PICU patients < 18 years of age with MODS were consented and peripheral blood samples were obtained as close to diagnosis as possible, 2 additional timepoints during ICU stay were also collected. Control samples were collected from age and sex matched patients. Total nucleated cells were extracted from EDTA tubes by RBC lysis. Cells were labeled with conjugated antibodies and run on a ZE5 flow cytometer, FACS analysis was performed using FlowJo software, stats were analyzed using MedCalc.

Results: We enrolled 14 patients with MODS, 10 having 3 or more collections. Diagnoses for the cohort of MODS patients included eosinophilic myocarditis, hemophagocytic lymphohistiocytosis (HLH), and cardiomyopathy. Average length of stay was 13.3 days with 12 of the 14 patients requiring mechanical ventilation. Other organ involvement included liver failure (6/14), acute kidney injury (8/14) and sepsis (11/14). FACS analysis revealed differences in multiple immunophenotypes between MODS patients and controls including a decrease in lymphocytes, T cells, and DCs along with increases in myeloid, activated neutrophils, and B cells. These data allowed for N=1 precision medicine observations with increased M2 macrophages and overall PD-1 expression in our patient diagnosed HLH.

Conclusions: Timely diagnosis, understanding of immune response and initiating prompt therapy is imperative for successfully managing MODS. We demonstrate the utility of flow cytometry for rapid, reliable, and relevant information about the status of the patients’ immune system.

Volume

53

Issue

1 Suppl.

DOI

10.1097/01.ccm.0001102888.81574.ed

ISSN

1530-0293

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