Ubiquitin fusion degradation protein 1 as a blood marker for the early diagnosis of ischemic stroke.
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.
Allard
Laure
L
Biomedical Proteomics Research Group, Department of Structural Biology and Bioinformatics, Medical University Center, CH-1211 Geneva 4, Switzerland.
Turck
Natacha
N
Burkhard
Pierre R
PR
Walter
Nadia
N
Rosell
Anna
A
Gex-Fabry
Marianne
M
Hochstrasser
Denis F
DF
Montaner
Joan
J
Sanchez
Jean-Charles
JC