Glucopeptides derived from myelin-relevant proteins and hyperglucosylated nontypeable Haemophilus influenzae bacterial adhesin cross-react with multiple sclerosis specific antibodies: A step forward in the identification of native autoantigens in multiple sclerosis |
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| Authors: | Michael Quagliata Francesca Nuti Feliciana Real-Fernandez Kalina Kirilova Kirilova Federica Santoro Alfonso Carotenuto Anna Maria Papini Paolo Rovero |
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| Affiliation: | 1. Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of Chemistry “Ugo Schiff”, University of Florence, Sesto Fiorentino, Italy;2. Institute of Chemistry of Organometallic Compounds (ICCOM), National Research Council of Italy (CNR), Sesto Fiorentino, Italy;3. Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of Chemistry “Ugo Schiff”, University of Florence, Sesto Fiorentino, Italy University of Burgos, Burgos, Spain;4. Department of Pharmacy, University of Naples “Federico II”, Naples, Italy;5. Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, University of Florence, Sesto Fiorentino, Italy |
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| Abstract: | Multiple sclerosis (MS) is an inflammatory and autoimmune disorder, in which an antibody-mediated demyelination mechanism plays a critical role. We prepared two glucosylated peptides derived from the human myelin proteins, that is, oligodendrocyte-myelin glycoprotein (OMGp) and reticulon-4 receptor (RTN4R), selected by a bioinformatic approach for their conformational homology with CSF114(Glc), a designed β-turn antigenic probe derived from myelin oligodendrocyte glycoprotein (MOG), a glycoprotein present in the CNS. This synthetic antigen is specifically recognized by antibodies in sera of MS patients. We report herein the antigenic properties of these peptides, showing, on the one hand, that MS patient antibodies recognize the two glucosylated peptides and, on the other hand, that these antibodies cross-react with CSF114(Glc) and with the previously described hyperglucosylated nontypeable Haemophilus influenzae bacterial adhesin protein HMW1ct(Glc). These observations point to an immunological association between human and bacterial protein antigens, underpinning the hypothesis that molecular mimicry triggers the breakdown of self-tolerance in MS and suggesting that RTN4R and OMGp can be considered as autoantigens. |
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| Keywords: | autoantibodies autoantigens glucopeptides molecular mimicry multiple sclerosis |
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