title: An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a complex disease that seems to depend on several pathophysiological processes. Because of its varied clinical presentation, natural history, and response to therapeutic interventions, MS can be considered to be a group of diseases that have not been yet characterized, thus resulting in difficult evaluation of prognosis. In the last few years, the role of autoAbs in MS has been reevaluated, and, therefore, their identification as specific biomarkers became a relevant target. In this paper, we demonstrate that an aberrant N-glucosylation is a fundamental determinant of autoAb recognition in MS. Thus, we developed CSF114(Glc), an antigenic probe accurately measuring IgM autoAbs in the sera of a patient population, as disease biomarker. The relevance of CSF114(Glc) is demonstrated by its clinical application and correlation with disease activity and prognosis. In fact, CSF114(Glc), a structure-based designed glycopeptide, is able to recognize, by ELISA, the presence of specific IgM autoAbs in the sera of a MS patient population but not in blood donors and other autoimmune conditions. AutoAbs specific for CSF114(Glc) isolated from MS patients recognized myelin and oligodendrocyte antigens by immunohistochemistry but not other nonrelevant tissues. We demonstrate that CSF114(Glc) is a reliable, specific probe in a longitudinal study of untreated MS patients. Development of IgG/IgM anti-CSF114(Glc) Abs paralleled clinical activity and brain lesions positive to MRI. Therefore, a CSF114(Glc)-based immunoassay on sera may have important prognostic value in monitoring MS disease progression guiding optimal therapeutic treatment.
authors: Laboratory of Peptide and Protein Chemistry and Biology, Polo Scientifico, University of Florence, I-50019 Sesto Fiorentino, Italy.
authors: Francesco
authors: F
authors: Lolli
authors: Barbara
authors: B
authors: Mulinacci
authors: Alfonso
authors: A
authors: Carotenuto
authors: Bruno
authors: B
authors: Bonetti
authors: Giuseppina
authors: G
authors: Sabatino
authors: Benedetta
authors: B
authors: Mazzanti
authors: Anna Maria
authors: AM
authors: D'Ursi
authors: Ettore
authors: E
authors: Novellino
authors: Marta
authors: M
authors: Pazzagli
authors: Laura
authors: L
authors: Lovato
authors: Maria C
authors: MC
authors: Alcaro
authors: Elisa
authors: E
authors: Peroni
authors: Maria C
authors: MC
authors: Pozo-Carrero
authors: Francesca
authors: F
authors: Nuti
authors: Luca
authors: L
authors: Battistini
authors: Giovanna
authors: G
authors: Borsellino
authors: Mario
authors: M
authors: Chelli
authors: Paolo
authors: P
authors: Rovero
authors: Anna Maria
authors: AM
authors: Papini
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D006020:Glycopeptides / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006020:Glycopeptides