Immune dysfunction in Rett syndrome patients revealed by high levels of serum anti-N(Glc) IgM antibody fraction.
Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology.
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy ; Laboratory of PeptLab-SOSCO-EA4505, University of Cergy-Pontoise, 5 mail Gay Lussac, 95031 Cergy-Pontoise CEDEX, France.
Anna Maria
AM
Papini
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy.
Francesca
0000-0001-9908-5996
F
Nuti
Toscana Biomarkers Srl, 53100 Siena, Italy.
Feliciana
F
Real-Fernandez
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Section of Pharmaceutical and Nutraceutical Sciences, Department NeuroFarBa, University of Florence, 50019 Sesto Fiorentino, Italy.
Giada
G
Rossi
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Section of Pharmaceutical and Nutraceutical Sciences, Department NeuroFarBa, University of Florence, 50019 Sesto Fiorentino, Italy.
Caterina
C
Tiberi
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy.
Giuseppina
G
Sabatino
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy.
Shashank
S
Pandey
Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), 53100 Siena, Italy ; Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Silvia
0000-0002-7027-1207
S
Leoncini
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Cinzia
0000-0003-0006-9414
C
Signorini
Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), 53100 Siena, Italy ; Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Alessandra
0000-0002-5207-068X
A
Pecorelli
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy ; Clinical Pathology Laboratory Unit, University Hospital, AOUS, 53100 Siena, Italy.
Roberto
0000-0003-3990-8991
R
Guerranti
Laboratory of BioMolecules, Sorbonne Université UPMC Paris 06, CNRS-ENS, 75005 Paris, France.
Solange
S
Lavielle
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Lucia
L
Ciccoli
Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy ; Section of Pharmaceutical and Nutraceutical Sciences, Department NeuroFarBa, University of Florence, 50019 Sesto Fiorentino, Italy.
Paolo
0000-0001-9577-5228
P
Rovero
Neonatal Intensive Care Unit, University Hospital, AOUS, 53100 Siena, Italy.
Claudio
0000-0002-9881-3119
C
De Felice
Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), 53100 Siena, Italy.
Joussef
J
Hayek
D000293:Adolescent; D000372:Agglutination Tests / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006020:Glycopeptides / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015518:Rett Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D006020:Glycopeptides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human