Antibodies from multiple sclerosis patients preferentially recognize hyperglucosylated adhesin of non-typeable Haemophilus influenzae
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Author(s)
Testa, Chiara
Eilam, Raya
Aharoni, Rina
Nuti, Francesca
Rossi, Giada
Real-Fernandez, Feliciana
Lanzillo, Roberta
Brescia Morra, Vincenzo
Lolli, Francesco
Rovero, Paolo
Date Issued
December 2016
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Walvoort, Marthe T. C. et al. “Antibodies from Multiple Sclerosis Patients Preferentially Recognize Hyperglucosylated Adhesin of Non-Typeable Haemophilus Influenzae.” Scientific Reports 6.1 (2016): n. pag.
Version
Final published version
Abstract
In autoimmune diseases, there have been proposals that exogenous “molecular triggers”, i.e., specific ‘non-self antigens’ accompanying infectious agents, might disrupt control of the adaptive immune system resulting in serious pathologies. The etiology of multiple sclerosis (MS) remains unclear. However, epidemiologic data suggest that exposure to infectious agents may be associated with increased MS risk and progression may be linked to exogenous, bacterially-derived, antigenic molecules, mimicking mammalian cell surface glycoconjugates triggering autoimmune responses. Previously, antibodies specific to a gluco-asparagine (N-Glc) glycopeptide, CSF114(N-Glc), were identified in sera of an MS patient subpopulation. Since the human glycoproteome repertoire lacks this uniquely modified amino acid, we turned our attention to bacteria, i.e., Haemophilus influenzae, expressing cell-surface adhesins including N-Glc, to establish a connection between H. influenzae infection and MS. We exploited the biosynthetic machinery from the opportunistic pathogen H. influenzae (and the homologous enzymes from A. pleuropneumoniae) to produce a unique set of defined glucosylated adhesin proteins. Interestingly we revealed that a hyperglucosylated protein domain, based on the cell-surface adhesin HMW1A, is preferentially recognized by antibodies from sera of an MS patient subpopulation. In conclusion the hyperglucosylated adhesin is the first example of an N-glucosylated native antigen that can be considered a relevant candidate for triggering pathogenic antibodies in MS.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1038/srep39430
