Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Brain Damage; Diagnosis; Plasma Markers; Stroke; UFD1.