Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), e.g. neurofascin, contactin, CNPase and other membrane anchored proteins. These putative antigens, although differing from the conventional myelin derivatives, are conceptually based on an animal model of experimental autoimmune encephalomyelitis. In this report we describe the identification of putative antigens based on their recognition by autoantibodies isolated from MuS patient serum. In a previous work from this laboratory we have shown that a peptide probe, named CSF114(Glc), specifically identifies serum autoantibodies in a subset of MuS patients, representing approximately 30% of the patient population. The autoantibodies, purified from MuS patients’ sera (six), through CSF114(Glc) affinity chromatography, detected three immunoreactive protein bands present in the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI and MS/MS techniques, revealed the presence of four proteins distinguishable by their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The immunoreactive profile of these rat brain proteins was compared with that of commercially available standard proteins by challenging against either CSF114(Glc) purified MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only Alpha actinin 1 as a putative antigen. In fact, Alpha actinin 1 displayed a robust immunoreactive response against all MuS patients’ sera examined, whereas the other three bands were not consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune hepatitis) might be regarded as a novel MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.

Alpha actinin is specifically recognized by multiple sclerosis autoantibodies isolated using an N-glucosylated peptide epitope / S. Pandey; I. Dioni; D. Lambardi; F. Real-Fernandez; E. Peroni; G. Pacini; F. Lolli; R. Seraglia; A. M. Papini; P. Rovero. - In: MOLECULAR & CELLULAR PROTEOMICS. - ISSN 1535-9484. - STAMPA. - 12:(2013), pp. 277-282. [10.1074/mcp.M112.017087]

Alpha actinin is specifically recognized by multiple sclerosis autoantibodies isolated using an N-glucosylated peptide epitope

REAL FERNANDEZ, FELICIANA;LOLLI, FRANCESCO;PAPINI, ANNA MARIA;ROVERO, PAOLO
2013

Abstract

Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), e.g. neurofascin, contactin, CNPase and other membrane anchored proteins. These putative antigens, although differing from the conventional myelin derivatives, are conceptually based on an animal model of experimental autoimmune encephalomyelitis. In this report we describe the identification of putative antigens based on their recognition by autoantibodies isolated from MuS patient serum. In a previous work from this laboratory we have shown that a peptide probe, named CSF114(Glc), specifically identifies serum autoantibodies in a subset of MuS patients, representing approximately 30% of the patient population. The autoantibodies, purified from MuS patients’ sera (six), through CSF114(Glc) affinity chromatography, detected three immunoreactive protein bands present in the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI and MS/MS techniques, revealed the presence of four proteins distinguishable by their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The immunoreactive profile of these rat brain proteins was compared with that of commercially available standard proteins by challenging against either CSF114(Glc) purified MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only Alpha actinin 1 as a putative antigen. In fact, Alpha actinin 1 displayed a robust immunoreactive response against all MuS patients’ sera examined, whereas the other three bands were not consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune hepatitis) might be regarded as a novel MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.
2013
12
277
282
S. Pandey; I. Dioni; D. Lambardi; F. Real-Fernandez; E. Peroni; G. Pacini; F. Lolli; R. Seraglia; A. M. Papini; P. Rovero
File in questo prodotto:
File Dimensione Formato  
MolCellProteomics_2013_12_277-282(Pandey).pdf

Accesso chiuso

Descrizione: Articolo principale
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 231.17 kB
Formato Adobe PDF
231.17 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/776704
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 13
social impact