Description:
<jats:sec><jats:title>Background</jats:title><jats:p> Efficacy of thrombolysis in acute ischemic stroke is strongly related to physician's ability to make an accurate diagnosis and to intervene within 3–6 h after event onset. In this context, the discovery and validation of very early blood markers have recently become an urgent, yet unmet, goal of stroke research. Ubiquitin fusion degradation protein 1 is increased in human postmortem CSF, a model of global brain insult, suggesting that its measurement in blood may prove useful as a biomarker of stroke. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Enzyme-linked immunosorbent assay (ELISA) was used to measure UFD1 in plasma and sera in three independent cohorts, European (Swiss and Spanish) and North-American retrospective analysis encompassing a total of 123 consecutive stroke and 90 control subjects. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Highly significant increase of ubiquitin fusion degradation protein 1 (UFD1) was found in Swiss stroke patients with 71% sensitivity (95% CI, 52–85.8%), and 90% specificity (95% CI, 74.2–98%) ( N = 31, p < 0.0001). Significantly elevated concentration of this marker was then validated in Spanish ( N = 39, p < 0.0001, 95% sensitivity (95% CI, 82.7– 99.4%)), 76% specificity (95% CI, 56.5–89.7%)) and North-American stroke patients ( N = 53, 62% sensitivity (95% CI, 47.9–75.2%), 90% specificity (95% CI, 73.5–97.9%), p < 0.0001). Its concentration was increased within 3 h of stroke onset, on both the Swiss ( p < 0.0001) and Spanish ( p = 0.0004) cohorts. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> UFD1 emerges as a reliable plasma biomarker for the early diagnosis of stroke, and in the future, might be used in conjunction with clinical assessments, neuroimaging and other blood markers. </jats:p></jats:sec>