Circulating blood cellular glucose transporters - Surrogate biomarkers for neonatal hypoxic-ischemic encephalopathy assessed by novel scoring systems.

Abstract

OBJECTIVE:

We examined Red Blood Cell (RBC) Glucose Transporter isoform 1 (GLUT1) and White Blood Cell (WBC) Glucose Transporter isoform 3 (GLUT3) protein concentrations to assess their potential as surrogate biomarkers for the presence of hypoxic-ischemic encephalopathy (HIE) and response to therapeutic hypothermia (TH), with respect to the neurodevelopmental prognosis.

STUDY DESIGN:

A prospective feasibility study of 10 infants with HIE and 8 age-matched control subjects was undertaken. Following parental consent, blood samples were obtained at baseline before institution of TH (<6 h of life), during TH, at rewarming and post-TH in the HIE group with a baseline sample from the control group. GLUT1 and GLUT3 were measured by Enzyme-linked immunosorbent assay (ELISA) with brain biomarkers, Neuron-Specific Enolase (NSE) and Glial Fibrillary Acidic Protein (GFAP). Novel "HIE-high risk" and "Neurological" scores were developed to help identify HIE and to assess severity and prognosis, respectively.

RESULTS:

RBC GLUT1 concentrations were increased at the baseline pre-TH time point in HIE versus control subjects (p = .006), normalizing after TH (p = .05). An association between GLUT1 and NSE concentrations (which was reflective of the HIE-high risk and the Neuro-scores) in controls and HIE pre-TH was seen (R2 = 0.36, p = .008), with GLUT1 demonstrating 90% sensitivity and 88% specificity for presence of HIE identified by Sarnat Staging. WBC GLUT3 concentrations were low and no different in HIE versus control, and GFAP concentrations trended higher during re-warming (p = .11) and post-TH (p = .16). We demonstrated a significant difference between HIE and controls for both the "HIE-high risk" and the "Neurological" Scores. The latter score revealing the severity of clinical neurological illness correlated with the corresponding RBC GLUT1 (R2 value = 0.39; p = .006).

CONCLUSION:

Circulating RBC GLUT1 concentrations with NSE demonstrate a significant potential in reflecting the severity of HIE pre-TH and gauging effectiveness of TH. In contrast, the low neonatal WBC GLUT3 concentrations make discerning differences between degrees of HIE as well as assessing effectiveness of TH difficult. The HIE-high risk and Neurological scores may extend the "Sarnat staging" towards assessing severity and neuro-developmental prognosis of HIE.

• Authors: Liesbeth V Maggiotto, Monica Sondhi, Bo-Chul Shin, Meena Garg, Sherin U Devaskar
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 127 Issue 2 Pg. 166-173 (06 2019) ISSN: 1096-7206 [Electronic] United States
• PMID: 31182397 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Biomarkers
• GFAP protein, human
• Glial Fibrillary Acidic Protein
• Glucose Transporter Type 1
• Glucose Transporter Type 3
• SLC2A1 protein, human
• SLC2A3 protein, human
• Phosphopyruvate Hydratase

Topics

• Biomarkers
• Erythrocytes (metabolism)
• Feasibility Studies
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Glucose Transporter Type 1 (metabolism)
• Glucose Transporter Type 3 (metabolism)
• Humans
• Hypoxia-Ischemia, Brain (diagnosis)
• Infant, Newborn
• Intensive Care Units, Neonatal
• Male
• Phosphopyruvate Hydratase (metabolism)
• Pilot Projects
• Prognosis
• Prospective Studies
• Sensitivity and Specificity
• Severity of Illness Index