Circulating immune cell landscape in patients who had mild ischaemic stroke

Abstract

Introduction: Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed, are excluded from treatment and in some cases clinically worsen. Circulating immune cells are potential biomarkers that can assist with diagnosis in ischaemic stroke. Understanding the transcriptomic changes of each cell population caused by ischaemic stroke is critical because they work closely in a complicated relationship. In this study, we investigated peripheral blood mononuclear cells (PBMCs) transcriptomics of patients who had a stroke using a single-cell RNA sequencing to understand peripheral immune response after mild stroke based on the gene expression in an unbiased way.

Methods: Transcriptomes of PBMCsfrom 10 patients who had an acute ischaemic stroke within 24 hours after stroke onset were compared with 9 race-matched/age-matched/gender-matched controls. Individual PBMCs were prepared with ddSeq^TM (Illumina-BioRad) and sequenced on the Illumina NovaSeq 6000 platform.

Results: Notable population changes were observed in patients who had a stroke, especially in NK cells and CD14+ monocytes. The number of NK cells was increased, which was further confirmed by flow cytometry. Functional analysis implied that the activity of NK cells also is enhanced in patients who had a stroke. CD14+ monocytes were clustered into two groups; dendritic cell-related CD14+ monocytes and NK cell-related CD14+ monocytes. We found CD14+ monocyte subclusters were dramatically reduced in patients who had a stroke.

Discussion: This is the first study demonstrating the increased number of NK cells and new monocyte subclusters of mild ischaemic stroke based on the transcriptomic analysis. Our findings provide the dynamics of circulating immune response that could assist diagnosis and potential therapeutic development of mild ischaemic stroke.

Trial registration: ClinicalTrials.gov NCT00009243 NCT00001846.

Keywords: inflammatory response; ischaemic attack; stroke; transient.