Abstract
The inflammasome is a key contributor to the inflammatory innate immune response after stroke. We have previously shown that inflammasome proteins are released in extracellular vesicles (EV) after brain and spinal cord injury. In addition, we have shown that inflammasome proteins offer great promise as biomarkers of central nervous system (CNS) injury following brain trauma. In the present study, we used a Simple Plex Assay (Protein Simple), a novel multi-analyte automated microfluidic immunoassay platform, to analyze serum and serum-derived EV samples from stroke patients and control subjects for inflammasome protein levels of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), Interleukins (IL)-1β, and (IL)-18. Receiver operator characteristic (ROC) curves with associated confidence intervals obtained from the analysis of serum samples revealed that the area under the curve (AUC) for ASC was 0.99 with a confidence interval between 0.9914 and 1.004, whereas the AUC for caspase-1, IL-1β, and IL-18 were 0.75, 0.61, and 0.67, respectively. Thus, these data indicate that ASC is a potential biomarker of stroke and highlight the role of the inflammasome in the inflammatory response after brain ischemia.
Highlights
The innate immune response is a well-known contributor to the inflammatory response after stroke (Xu and Jiang, 2014; Brand et al, 2015; Neumann et al, 2015)
Previous work on the inflammasome has indicated that inflammasome proteins can be used as biomarkers after traumatic brain injury (Adamczak et al, 2012) and multiple sclerosis (Keane et al, 2018)
The inflammasome is a multiprotein complex of the innate immune response involved in the activation of caspase-1 and the processing of the inflammatory cytokines IL-1β and IL18
Summary
The innate immune response is a well-known contributor to the inflammatory response after stroke (Xu and Jiang, 2014; Brand et al, 2015; Neumann et al, 2015). We have previously shown that the inflammasome, an arm of the innate immune response involved in the activation of caspase-1 and the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, contributes to the pathology of stroke (Abulafia et al, 2009). Therapeutic targeting of the inflammasome has been shown to improve outcomes after Central Nervous System (CNS) injury, including stroke (Brand et al, 2016). Biomarkers in blood or other body fluids can be used as indicators of stroke onset. To date, there is no biomarker available that is used in the diagnosis and management of stroke
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