Projects / Autism Spectrum Disorders / Rett Syndrome

Autoantibodies to N-glucosylated peptide sequons in Rett syndrome


In collaboration with:

Child Neuropsychiatry Unit, University Hospital AOUS of Siena, Italy

Joussef Hayek

Neonatal Intensive Care Unit, University Hospital AOUS of Siena,  Italy

Claudio De Felice

Toscana Biomarkers S.r.l. Via Fiorentina,  Siena; Italy

Feliciana Real Fernandez

Rett syndrome (RTT), an X-linked neurodevelopment disorder affecting predominantly females, has received great attention for the devastating consequences that it inflicts on young children.

RTT is specifically characterized by loss of acquired purposeful hand skills, loss of acquired spoken language, gait dyspraxia and stereotypic hand movements. Up to 95% of typical RTT cases are caused by mutations in the methyl-CpG binding protein 2 (MeCP2),1 a gene located in the Xq28 region of the human genome that encodes a protein whose full list of functions still remains unknown. Up to now the pathogenetic mechanisms leading from gene mutation to disease expression remain to be clarified.

RTT has recently been proposed as a model of Mutiple Sclerosis (MS), a severe neurological progressive disease. In this project the presence of a statistically significant autoimmune primary response against anti Asn-Glucosylated epitopes in 182 RTT patients versus 72 healthy controls has been detected for the first time. These data are the first insight that aberrant N-glucosylation of sequons could trigger an early inflammatory autoimmune response impairing neurodevelopment / neurodegenerative conditions.



J. Hayek, C. De Felice, A.M. Papini, P. Rovero, F. Nuti, F. Real-Fernandez, G. Sabatino, C. Tiberi (2012). Nuovi peptidi glicosilati. Azienda Ospedaliera Universitaria Senese. Licensed to Toscana Biomarkers (Italy).



doi: 10.1155/2014/260973


Immune dysfunction in Rett syndrome patients revealed by high levels of serum anti-N(Glc) IgM antibody fraction.

A.M. Papini, F. Nuti, F. Real-Fernandez, G. Rossi, C. Tiberi, G. Sabatino, S. Pandey, S. Leoncini, C. Signorini, A. Pecorelli, R. Guerranti, S. Lavielle, L. Ciccoli, P. Rovero, C. De Felice, and J. Hayek. J.Immunol.Res. (2014) 2014:260973.