Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke

TY - JOUR

T1 - Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke

AU - Zangari, Rosalia

AU - Zanier, Elisa R

AU - Torgano, G

AU - Bersano, A

AU - Beretta, S

AU - Beghi, Ettore

AU - Casolla, B

AU - Checcarelli, N

AU - Lanfranconi, S

AU - Maino, A

AU - Mandelli, C

AU - Micieli, G

AU - Orzi, F

AU - Picetti, E

AU - Silvestrini, M

AU - Stocchetti, Nino

AU - Zecca, B

AU - Garred, P

AU - De Simoni, Maria-Grazia

AU - LEPAS group

PY - 2016/1/20

Y1 - 2016/1/20

N2 - Background: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. Methods: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). Results: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001). Conclusions: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.

AB - Background: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. Methods: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). Results: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001). Conclusions: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.

KW - Adult

KW - Age Factors

KW - Aged

KW - Brain Ischemia

KW - Case-Control Studies

KW - Cohort Studies

KW - Female

KW - Humans

KW - Italy

KW - Lectins

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Regression Analysis

KW - Risk Factors

KW - Severity of Illness Index

KW - Statistics, Nonparametric

KW - Stroke

KW - Time Factors

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/s12974-016-0481-2

DO - 10.1186/s12974-016-0481-2

M3 - Journal article

C2 - 26792363

SN - 1742-2094

VL - 13

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

M1 - 16

ER -