Plasma Protein Profiling by Proximity Extension Assay Technology Reveals Novel Biomarkers of Traumatic Brain Injury-A Pilot Study.

Abstract

Traumatic brain injury (TBI) is a significant public health issue affecting nearly 69 million patients worldwide per year. Reliable diagnostic biomarkers are urgently needed to aid in disease diagnosis and prognosis and to guide patient aftercare. Blood biomarkers represent an attractive modality to quickly, cheaply, and objectively evaluate clinical status. We hypothesize that deep and quantitative plasma proteomic profiling with a novel technology, proximity extension assay, may lead to the discovery of diagnostic and/or prognostic biomarkers of TBI. We used high-throughput proximity extension assays (PEA) to quantify the relative abundance of over 1000 unique proteins in plasma. PEA is a highly sensitive multiplex immunoassay capable of detecting very low-abundance proteins (down to fg/mL) in complex biological matrices. Our patient cohort consisted of severe TBI (sTBI) patients, matched healthy controls, and another non-TBI group that was included in the analysis to validate the specificity of the candidates during the selection process. The obtained protein quantification data was then filtered to identify candidate biomarkers through statistical analysis, literature searches, and comparison to our reference control groups. Overall, we identified 6 novel candidate TBI biomarkers. Candidates exhibit a significant increase in plasma protein abundance in sTBI when comparing between healthy controls and sTBI patients. Candidates generally had low expression in our reference groups compared with the sTBI group. Our preliminary findings represent a starting point for future validation. These biomarkers, either alone or in combination, may have significant clinical utility in aiding in TBI diagnosis, prognosis, and/or management.