Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation

ABSTRACT

Objective: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. Methods: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status.Results: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72–95%) sensitivity and 75% (95% CI = 51–91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group. Conclusions: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia.

KEYWORDS:

• cfDNA
• cerebrovascular disease
• biomarker
• emergency medicine
• brain injury
• NLR

Acknowledgements

The authors would foremost like to thank the subjects and their families, as this work was truly made possible by their selfless contribution. They also would like to thank the stroke team at Ruby Memorial Hospital for their invaluable support.

Declarations of Interest

The work was funded via a Robert Wood Johnson Foundation nurse faculty scholar award to TLB (70319) and a National Institutes of Health CoBRE sub-award to TLB (P20 GM109098). GCO and TLB have a patent pending re: markers of stroke and stroke severity. TLB serves as chief scientific officer for Valtari Bio Incorporated. Work by GCO is part of a pending licensing agreement with Valtari Bio Incorporated. The remaining authors report no potential conflicts of interest.

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