title: Plasma biomarkers discriminate clinical forms of multiple sclerosis.
abstract: Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Tejera-Alhambra
authors.affiliation: Department of Immunology, Center for Human Immunology, Institut Pasteur, Paris, France; Department of Immunology, INSERM U818, Institut Pasteur, Paris, France.
authors.forename: Armanda
authors.initials: A
authors.lastname: Casrouge
authors.affiliation: Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: de Andrés
authors.affiliation: STAT-UP Statistical Consulting&Services, Madrid, Spain.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Seyfferth
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ramos-Medina
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Center Alicia Koplowitz for Multiple Sclerosis of the Community of Madrid, Madrid, Spain.
authors.forename: Janet
authors.initials: J
authors.lastname: Vega
authors.affiliation: Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Fernández-Paredes
authors.affiliation: Department of Immunology, Center for Human Immunology, Institut Pasteur, Paris, France; Department of Immunology, INSERM U818, Institut Pasteur, Paris, France.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sánchez-Ramón
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054413:Chemokine CCL11 / Q000097:blood*; D054407:Chemokine CCL4 / Q000097:blood*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D004815:Epidermal Growth Factor / Q000097:blood*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000175:diagnosis*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: D015415:Biomarkers; C515456:CCL11 protein, human; C066507:CCL4 protein, human; D054413:Chemokine CCL11; D054407:Chemokine CCL4; C066855:HGF protein, human; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor