Chantler, P. D. | bioRxiv Science

bioRxiv2017

Monocyte-Lymphocyte Cross-Communication Via Soluble CD163 Directly Links Innate Immune System Activation And Adaptive Immune System Suppression Following Ischemic Stroke

CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

neuroscience↗

bioRxiv2017

Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population.

PurposeOur group recently identified a ten gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population.\n\nMethodsPublically available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset, along with 23 cardiovascular disease controls were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes were extracted, compared between groups, and evaluated for their discriminatory ability at each time point.\n\nResultsWe observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points.\n\nConclusionsThese findings confirm the diagnostic robustness of the previously identified pattern of differential expression in independent patient population, and further suggest that it is temporally stable over the first 24 hours of stroke pathology.

genomics↗