title: Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis.
abstract: Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-β-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression.
authors.affiliation: From the ‡Proteomics Unit, Centre de Regulació Genòmica (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; §Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain;
authors.forename: Eva
authors.initials: E
authors.lastname: Borràs
authors.affiliation: ¶Servei de Neurologia-Neuroimmunologia. Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Institut de Receca Vall d'Hebron (VHIR). Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona. Barcelona, Spain;
authors.forename: Ester
authors.initials: E
authors.lastname: Cantó
authors.affiliation: ‖Department of Statistics, Purdue University, West Lafayette, IN, USA;
authors.forename: Meena
authors.initials: M
authors.lastname: Choi
authors.affiliation: **Department of Neurology and Immunology, Hospital Ramón y Cajal, Ctra. de Colmenar Viejo, km. 9,100, Madrid, 28034, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Maria Villar
authors.affiliation: **Department of Neurology and Immunology, Hospital Ramón y Cajal, Ctra. de Colmenar Viejo, km. 9,100, Madrid, 28034, Spain.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Álvarez-Cermeño
authors.affiliation: From the ‡Proteomics Unit, Centre de Regulació Genòmica (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; §Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain;
authors.forename: Cristina
authors.initials: C
authors.lastname: Chiva
authors.affiliation: ¶Servei de Neurologia-Neuroimmunologia. Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Institut de Receca Vall d'Hebron (VHIR). Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona. Barcelona, Spain;
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: ‖Department of Statistics, Purdue University, West Lafayette, IN, USA;
authors.forename: Olga
authors.initials: O
authors.lastname: Vitek
authors.affiliation: ¶Servei de Neurologia-Neuroimmunologia. Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Institut de Receca Vall d'Hebron (VHIR). Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona. Barcelona, Spain; eduard.sabido@crg.cat manuel.comabella@vhir.org.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.affiliation: From the ‡Proteomics Unit, Centre de Regulació Genòmica (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain; §Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain; eduard.sabido@crg.cat manuel.comabella@vhir.org.
authors.forename: Eduard
authors.initials: E
authors.lastname: Sabidó
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid; D000595:Amino Acid Sequence; D000071451:Chitinase-3-Like Protein 1; D003937:Diagnosis, Differential; D004150:Dipeptidases / Q000134:cerebrospinal fluid; D018450:Disease Progression; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism*; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism*; D010455:Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D011379:Prognosis; D020543:Proteome / Q000145:classification / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013577:Syndrome
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D010455:Peptides; D020543:Proteome; D004150:Dipeptidases; C038937:dipeptidase