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

Francesco Lolli, Barbara Mulinacci, Alfonso Carotenuto, Bruno Bonetti, Giuseppina Sabatino, Benedetta Mazzanti, Anna Maria D'Ursi, Ettore Novellino, Marta Pazzagli, Laura Lovato, Maria C. Alcaro, Elisa Peroni, Maria C. Pozo-Carrero, Francesca Nuti, Luca Battistini, Giovanna Borsellino, Mario Chelli, Paolo Rovero, Anna Maria Papini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)10273-10278
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number29
DOIs
Publication statusPublished - Jul 19 2005

Keywords

  • β-hairpin
  • Aberrant glycosylation
  • Prognostic probe
  • Synthetic antigen

ASJC Scopus subject areas

  • Genetics
  • General

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