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A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury
Journal article   Open access   Peer reviewed

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury

Sterling B Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O Torres, Uma M Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman and Ann M Stowe
Critical care medicine, Vol.47(3), pp.e206-e213
03/2019
DOI: 10.1097/CCM.0000000000003621
PMCID: PMC6377324
PMID: 30640221
url
https://doi.org/10.1097/CCM.0000000000003621View
Published (Version of record) Open Access

Abstract

Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury. A single center prospective observational study. Pediatric and cardiac ICUs at a single tertiary care, academic center. Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients INTERVENTIONS:: None. Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10-23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p < 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation. We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS.
 Flow Cytometry T-Lymphocytes, Cytotoxic - immunology Humans Child, Preschool Infant Male Extracorporeal Membrane Oxygenation - adverse effects Inflammation - immunology Brain Injuries - therapy Drug Discovery Inflammation - etiology Case-Control Studies Pilot Projects B-Lymphocytes - immunology Brain Injuries - immunology Adolescent Female Organ Dysfunction Scores Adaptive Immunity - immunology Brain - immunology Child Infant, Newborn

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