Multiple Sclerosis, molecular mechanisms and bacterial infections

The etiopathogenesis of Multiple Sclerosis (MS) is still an unknown debated question. One of the most relevant hypothesis considers the possible involvement of bacterial infections triggering at the molecular level an autoimmune response and therefore the manifestation of the disease.

This is the pathway that has been followed by an international research team led by Anna Maria Papini from the Department of Chemistry of the University of Florence and that was recently published in Nature Scientific Reports (“Antibodies from multiple sclerosis patients preferentially recognize hyperglucosylated adhesin of non-typeable Haemophilus influenzae” — DOI: 10.1038/srep39430).

“Antibodies present in blood of patients affected by MS recognise specifically the protein adhesin produced by the bacterium Haemophilus influenzae in a hyperglucosylated form”, clarifies Anna Maria Papini. “Our data indicate for the first time that a bacterial protein could be one of the native antigen leading to the production of antibodies by stimulating the immune system.”

The study is part of a stream of research initiated in 1995 with the ”Project Multiple Sclerosis”, funded by the Italian Higher Institute of Health (ISS), to investigate the molecular mechanisms of MS. The project led to the establishment of the Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology of the University of Florence.

“These results are connected to the original observation, published by our team in 1999, that synthetic peptides characterised by “hairpin structures”, but only those bearing glucose moiety on the tip of the hairpin, are able to recognise serum antibodies in MS patients”, A.M. Papini points out. “The new results show that the peptides previously described, mimic portions of the bacterial hyperglucosylated adhesin, paving the way of a molecular mimicry mechanism by which human proteins become the target of specific antibodies in MS”.

The project was developed in tight collaboration with researchers from MIT (Boston, USA), the Weizmann Institute of Science (Rheovot, Israel) and the Multiple Sclerosis Centre of the University of Naples Hospital.

Co-sponsors of the study were also Fondazione Cassa di Risparmio di Firenze and Regione Toscana (MARK project: “Identification of diagnostic biomarkers for immune system-mediated diseases”).