Abstract
BackgroundThe inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels.Methods and findingsHere we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE).ConclusionThese findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI.
Highlights
A biomarker is a surrogate indicator of biological processes occurring in an individual
We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels
We extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18
Summary
A biomarker is a surrogate indicator of biological processes occurring in an individual. The Brain Trauma Indicator has been authorized by the FDA to evaluate concussion in adults. Other promising biomarkers have been suggested for diagnosis, monitoring and prognosis of traumatic brain injury (TBI) such as microtubule-associated protein-2 (MAP2, neuron-specific enolase (NSE), myelin basic protein (MBP), tau, s100β and neurofilament heavy chain protein (NF-H) [4,5,6]. These proteins are yet to be approved for the clinical care of TBI patients. Heart fatty acid binding protein (H-FABP), when combined with interleukin (IL)-10, S100β and GFAP, has been shown to be elevated in patients positive for brain damage as determined by a head CT scan [7]
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