Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke
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ORIGINAL ARTICLE
Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke Candice M. Brown 1 & Cheryl D. Bushnell 2 & Gregory P. Samsa 3 & Larry B. Goldstein 4 & Carol A. Colton 5
Received: 6 May 2015 / Revised: 1 September 2015 / Accepted: 2 September 2015 / Published online: 15 September 2015 # Springer Science+Business Media New York 2015
Abstract The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks poststroke compared to control individuals. Cases were AfricanAmericans with lacunar stroke (n=30), and controls were agematched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained >6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n=5) and controls (n=4). After adjustment for covariates, the pro-inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune * Candice M. Brown [email protected] 1
Department of Neurobiology and Anatomy, Center for Basic and Translational Stroke Research, and Center for Neuroscience, West Virginia University School of Medicine, Box 9128, Morgantown, WV 26506, USA
2
Department of Neurology, One Medical Center Boulevard, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
3
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Box 2721, Durham, NC 27110, USA
4
Department of Neurology and Kentucky Neuroscience Institute, University of Kentucky, 740 S. Limestone Street, Room L445, Lexington, KY 40536, USA
5
Department of Neurology, Duke University Medical Center, Box 2900, Durham, NC 27710, USA
responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM-1 and TAT and an abnormal response to acute immune challenge >6 weeks post-stroke, suggesting a chronically compromised systemic inflammatory response. Keywords Small vessel disease . Lacunar stroke . African-Americans . Chronic inflammation . Race-ethnic disparities . Biomarkers
Background About 795,000 people in the USA have strokes each year, with African-Americans having two times the risk of stroke as whites, especially at younger ages [1, 2]. African-Americans are also more likely to have silent lacunar infarcts on MRI compared to whites and are three times more likely to have lacunar strokes [3]. The reasons for this disparity are not fully explained by the differences in common risk factors, nor are the underlying mechanisms known. Peripheral inflammatory processes
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