title: Plasmatic retinol-binding protein 4 and glial fibrillary acidic protein as biomarkers to differentiate ischemic stroke and intracerebral hemorrhage.
abstract: A rapid differentiation of acute ischemic stroke and intracerebral hemorrhage (ICH) is essential for an adequate treatment and to promote a better outcome. Our aim was to identify new plasma biomarkers to differentiate stroke subtypes and to combine their diagnostic ability with other biomarkers already described for this clinical indication. Plasma samples of ischemic stroke patients (36) and ICH patients (10) were screened using a 177 antibodies library, and 11 showed different concentrations among stroke subtypes (p < 0.05), mainly chemokines, growth factors and angiogenic factors. Five proteins were selected for replication in 16 ischemic stroke patients and 16 ICH patients, and retinol-binding protein 4 (RPB4), apolipoprotein B100 and pigment epithelial-derived factor were replicated (p < 0.05). These proteins, together with glial fibrillary acidic protein (GFAP) and receptor for advanced glycation end product, were tested in 38 ischemic stroke and 28 ICH samples. Finally, RBP4 >61 μg/mL and GFAP <0.07 ng/mL showed a specificity of 100% for both subtypes. Moreover, after multivariate logistic regression analysis, RBP4 >48.75 μg/mL (ORadj : 6.09 (1.3-28.57), p = 0.02) and GFAP <0.07 ng/mL (ORadj : 0.03 (0.003-0.31), p = 0.003) resulted in independent predictors of stroke subtype, improving discrimination by 29% (p < 0.0001). Both biomarkers might be useful as diagnostic biomarkers to differentiate ischemic stroke and ICH. A rapid differentiation of ischemic stroke from intracerebral hemorrhage is essential to provide the appropriate treatment. We describe the discovery and subsequent replications of RBP4 and its combination with circulating GFAP as plasmatic biomarkers for hyperacute stroke subtype differentiation. The combination of these biomarkers and others might aid to speed up the discrimination of both stroke subtypes improving the outcome of patients.
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Llombart
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: García-Berrocoso
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bustamante
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Giralt
authors.affiliation: Neurovascular Unit, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Luna
authors.affiliation: Neurovascular Unit, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Muchada
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Boada
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications; D002543:Cerebral Hemorrhage / Q000097:blood*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D020521:Stroke / Q000097:blood* / Q000209:etiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020543:Proteome; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma
keywords: biomarkers; cerebral ischemia; intracerebral hemorrhage; stroke subtype