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 C Morriss, Fenghua Tian, Lakshmi Raman, Ann M Stowe

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: 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. DESIGN: A single center prospective observational study. SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center. PATIENTS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)e206-e213
JournalCritical care medicine
Volume47
Issue number3
DOIs
StatePublished - Mar 1 2019

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Extracorporeal Membrane Oxygenation
Adaptive Immunity
Brain Injuries
Pediatrics
Brain
Homeostasis
Organ Dysfunction Scores
Near-Infrared Spectroscopy
Interleukin-8
Tertiary Care Centers
Observational Studies
Flow Cytometry
B-Lymphocytes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury. / Ortega, Sterling B.; Pandiyan, Poornima; Windsor, Jana; Torres, Vanessa O.; Selvaraj, Uma M.; Lee, Amy; Morriss, Michael C; Tian, Fenghua; Raman, Lakshmi; Stowe, Ann M.

In: Critical care medicine, Vol. 47, No. 3, 01.03.2019, p. e206-e213.

Research output: Contribution to journalArticle

Ortega, Sterling B. ; Pandiyan, Poornima ; Windsor, Jana ; Torres, Vanessa O. ; Selvaraj, Uma M. ; Lee, Amy ; Morriss, Michael C ; Tian, Fenghua ; Raman, Lakshmi ; Stowe, Ann M. / A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury. In: Critical care medicine. 2019 ; Vol. 47, No. 3. pp. e206-e213.
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AU - Ortega, Sterling B.

AU - Pandiyan, Poornima

AU - Windsor, Jana

AU - Torres, Vanessa O.

AU - Selvaraj, Uma M.

AU - Lee, Amy

AU - Morriss, Michael C

AU - Tian, Fenghua

AU - Raman, Lakshmi

AU - Stowe, Ann M

PY - 2019/3/1

Y1 - 2019/3/1

N2 - OBJECTIVES: 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. DESIGN: A single center prospective observational study. SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center. PATIENTS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

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