Projects / Autoimmune mediate diseases / Multiple Sclerosis

An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis

Profiles

In collaboration with:

Department of Pharmaceutical and Toxicological Chemistry, University of Naples ‘‘Federico II,’’  Naples, Italy

Alfonso Carotenuto, Ettore Novellino

Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy

Anna Maria D’Ursi

Toscana Biomarkers Srl, I-53100 Siena, Italy

Maria C. Alcaro

Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, Neuroimmunology Unit, Rome, Italy

Luca Battistini, Giovanna Borsellino

Department of Neurological Sciences and Vision, University of Verona, Ospedale Policlinico G.B. Rossi, Verona, Italy

Bruno Bonetti, Laura Lovato

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 non relevant tissues. We demonstrate that CSF114(Glc) is a reliable, specific probe in a longitudinal study of untreated MS patients.

Therefore, a CSF114(Glc)-based immunoassay on sera may have important prognostic value in monitoring MS disease progression guiding optimal therapeutic treatment.