Aptamer-based proteomics in pediatric patients with severe traumatic brain injury: a pilot study
Bradley J De Souza1, Michael S Wolf2, Jeffrey R Leonard3
1Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA. bdesouza@chla.usc.edu.
Insights
Aptamer-based proteomics identified 634 proteins changing over time after severe traumatic brain injury (sTBI) in children. These dynamic proteomic profiles predict neurological outcomes, offering insights for precision neurocritical care.
Area of Science:
- Neuroscience
- Proteomics
- Biomarker Discovery
Background:
- Severe traumatic brain injury (sTBI) in children is a significant cause of death and disability.
- Understanding the molecular biology and prognostic indicators of pediatric sTBI is crucial but incomplete.
- Aptamer-based proteomics offers a high-throughput method to analyze molecular responses and identify biomarkers.
Purpose of the Study:
- To characterize temporal changes in the plasma proteome following pediatric sTBI.
- To evaluate the relationship between these proteomic changes and short-term neurological outcomes.
- To explore the potential of aptamer-based proteomics for biomarker discovery and outcome prediction in pediatric sTBI.
Main Methods:
- Prospective, repeated-measures case-control pilot study.
- Plasma samples collected from pediatric sTBI patients (n=24) at 24 and 72 hours post-injury and from healthy controls (n=4).
- Aptamer-based assay measuring 1297 proteins, analyzed using principal component analysis, differential expression testing, and pathway enrichment. Outcome assessment via GOS-E Peds scores.
Main Results:
- 634 proteins exhibited significant temporal changes, including novel and established biomarkers.
- Proteomic profiles in sTBI patients diverged from controls, with maximal divergence at 72 hours.
- Distinct protein panels accurately predicted GOS-E Peds outcomes at discharge (R²=0.84) and 3 months (R²=0.88), with age being a significant variable.
Conclusions:
- Temporally resolved plasma proteomics can reveal evolving brain and systemic responses after pediatric sTBI.
- These dynamic proteomic shifts correlate with short-term neurological outcomes.
- High-dimensional proteomic profiling shows clinical potential for biomarker discovery, molecular phenotyping, and precision medicine in pediatric neurocritical care.
Background:
Severe traumatic brain injury (sTBI) in children is a major cause of morbidity and mortality, yet its biology and prognostic indicators remain partially defined. Aptamer-based proteomics enables high-throughput characterization of molecular responses and may reveal biomarkers that improve injury characterization and outcome prediction.
Methods:
In this prospective, repeated-measures case-control pilot study, we characterized temporal changes in the plasma proteome after pediatric sTBI and evaluated their relationship to short-term outcomes. Plasma samples from children with sTBI (n = 24) were collected at 24- and 72-hours after injury and compared with healthy controls (n = 4). Samples were analyzed using an aptamer-based assay measuring 1297 proteins. Principal component analysis, differential expression testing, and pathway enrichment were performed. Associations with Glasgow Outcome Scale - Extended, Pediatric Revision (GOS-E Peds) scores at hospital discharge and 3-months were examined.
Results:
634 proteins showed significant temporal changes, including established and novel biomarkers. Proteomic profiles diverged from controls, greatest at 72 hours. Age accounted for substantial variability within sTBI patients. Distinct protein panels predicted GOS-E Peds outcomes at discharge (R2 = 0.84) and 3-months (R2 = 0.88).
Conclusion:
Temporally resolved plasma proteomics may identify evolving brain and systemic responses after pediatric sTBI that are associated with short-term outcomes.
Impact:
Temporally resolved aptamer-based plasma proteomics reveal dynamic shifts in brain-specific and systemic signaling after pediatric severe traumatic brain injury (sTBI) and correlate with short-term neurologic outcomes. We identify 634 proteins with significant temporal changes, including both established and novel biomarkers, and show that age is a major determinant of proteomic variability in patients with sTBI. This study demonstrates the feasibility and clinical potential of high-dimensional proteomic profiling for biomarker discovery, molecular phenotyping, and potential for outcome prediction, informing future precision medicine approaches in pediatric neurocritical care.
