Traumatic brain injury (TBI) is a leading cause of death in the US, and treatment options are limited. Therapeutic clinical trials in TBI have yielded disappointing results owing in part to the difficulty in accounting for clinically important heterogeneity within TBI. Early delivery of therapy is essential after TBI to reduce secondary brain injury, but unrestricted treatment of all brain injuries could be harmful. TBI stimulates a complex cascade of immunologic responses, both centrally and peripherally. These peripheral immune responses to TBI could serve as an early sensor of risk phenotype given the rapid, readily measurable response in the blood. An improved ability to risk-stratify patients on admission will streamline patient selection for aggressive interventions—such as invasive neuromonitoring—versus selection of those patients who can safely be observed reducing potential harms.
The purpose of the project is to develop supervised learning models of actionable short- and long-term outcomes post-TBI and to interrogate if pre-specified immunoregulatory proteins add predictive power to the models over clinical features alone.
Dr. Holly E. Hinson, a neurologist and neurointensivist at OHSU, hypothesizes that immunoregulatory proteomic signatures improve our ability to classify a low-risk clinical phenotype after TBI. Her preliminary data suggest peripheral cytokine levels are associated with actionable clinical events acutely after TBI.
Dr. Jon Jacobs a biochemist and staff scientist at PNNL, will help lead the application of the proteomic analysis platforms towards the clinical phenotype characterization of TBI.
The team will use a highly-sensitive, single molecule immunoarray (SIMOA) to detect immunoregulatory proteins complemented with an unbiased proteomic approach utilizing global discovery mass spectrometry (MS) based upon the sensitive MS platforms available at PNNL.
Dr. Hinson will develop and assess a series of models incorporating proteomic signatures to classify:
Hinson HE, Jacobs J, McWeeney S, Wachana A, Shi T, Martin K, Rodland K. Antibody-Free Mass Spectrometry Identification of Vascular Integrity Markers in Major Trauma. Neurotrauma Rep. 2021 Jul 1;2(1):322-329. doi: 10.1089/neur.2021.0007. PMID: 34318300; PMCID: PMC8310742.