title: Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke.
abstract: 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.
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. rosalia.zangari@guest.marionegri.it.|Department of physiopathology and transplant, Milan University and Neuro ICU Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. rosalia.zangari@guest.marionegri.it.
authors.forename: R
authors.initials: R
authors.lastname: Zangari
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. elisa.zanier@marionegri.it.
authors.forename: E R
authors.initials: ER
authors.lastname: Zanier
authors.affiliation: Emergency Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. giuseppe.torgano@policlinico.mi.it.
authors.forename: G
authors.initials: G
authors.lastname: Torgano
authors.affiliation: Cerebrovascular Disease Unit, IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy. anna.bersano@istituto-besta.it.
authors.forename: A
authors.initials: A
authors.lastname: Bersano
authors.affiliation: Department of Neurology, San Gerardo Hospital, Milan Center for Neuroscience, University of Milano Bicocca, Monza, Italy. simone.beretta@unimib.it.
authors.forename: S
authors.initials: S
authors.lastname: Beretta
authors.affiliation: Department of physiopathology and transplant, Milan University and Neuro ICU Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. ettore.beghi@marionegri.it.
authors.forename: E
authors.initials: E
authors.lastname: Beghi
authors.affiliation: Department NESMOS, University of Rome "La Sapienza", Rome, Italy. barbara.casolla@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Casolla
authors.affiliation: Valduce Hospital Como, Como, Italy. nicolettache@yahoo.com.
authors.forename: N
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authors.lastname: Checcarelli
authors.affiliation: Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. silvia.lanfranconi@policlinico.mi.it.
authors.forename: S
authors.initials: S
authors.lastname: Lanfranconi
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. alberto.maino@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Maino
authors.affiliation: Emergency Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. clara.mandelli@policlinico.mi.it.
authors.forename: C
authors.initials: C
authors.lastname: Mandelli
authors.affiliation: C. Mondino National Neurological Institute, Pavia, Italy. giuseppe.micieli@mondino.it.
authors.forename: G
authors.initials: G
authors.lastname: Micieli
authors.affiliation: Department NESMOS, University of Rome "La Sapienza", Rome, Italy. francesco.orzi@uniroma1.it.
authors.forename: F
authors.initials: F
authors.lastname: Orzi
authors.affiliation: Division of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. edoardopicetti@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Picetti
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy. m.silvestrini@univpm.it.
authors.forename: M
authors.initials: M
authors.lastname: Silvestrini
authors.affiliation: Department of physiopathology and transplant, Milan University and Neuro ICU Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. stocchet@policlinico.mi.it.
authors.forename: N
authors.initials: N
authors.lastname: Stocchetti
authors.affiliation: Emergency Care Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. bruno.zecca@policlinico.mi.it.
authors.forename: B
authors.initials: B
authors.lastname: Zecca
authors.affiliation: Laboratory of Moleclar Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark. garred@post5.tele.dk.
authors.forename: P
authors.initials: P
authors.lastname: Garred
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. mariagrazia.desimoni@marionegri.it.
authors.forename: M G
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy; D037102:Lectins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D013997:Time Factors; D000097604:Ficolins
chemical_list: D037102:Lectins; D000097604:Ficolins