An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis.
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.
Lolli
Francesco
F
Laboratory of Peptide and Protein Chemistry and Biology, Polo Scientifico, University of Florence, I-50019 Sesto Fiorentino, Italy.
Mulinacci
Barbara
B
Carotenuto
Alfonso
A
Bonetti
Bruno
B
Sabatino
Giuseppina
G
Mazzanti
Benedetta
B
D'Ursi
Anna Maria
AM
Novellino
Ettore
E
Pazzagli
Marta
M
Lovato
Laura
L
Alcaro
Maria C
MC
Peroni
Elisa
E
Pozo-Carrero
Maria C
MC
Nuti
Francesca
F
Battistini
Luca
L
Borsellino
Giovanna
G
Chelli
Mario
M
Rovero
Paolo
P
Papini
Anna Maria
AM
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*
D001323:Autoantibodies; D015415:Biomarkers; D006020:Glycopeptides