title: Transketolase and 2',3'-cyclic-nucleotide 3'-phosphodiesterase type I isoforms are specifically recognized by IgG autoantibodies in multiple sclerosis patients.
abstract: The presence of autoantibodies in multiple sclerosis (MuS) is well known, but their target antigens have not been clearly identified. In the present study, IgG autoreactivity to neural antigens of normal human white matter separated by bidimensional electrophoresis was assessed in serum and cerebrospinal fluid of 18 MuS and 20 control patients. Broad IgG autoreactivity was detected by two-dimensional immunoblotting in all cases to neural antigens, most of which were identified by mass spectrometry. The comparative analysis of MuS and non-MuS reactive spots showed that a restricted number of neural protein isoforms were specifically recognized by MuS IgG. Almost all MuS patients had cerebrospinal fluid IgG directed to isoforms of one of the oligodendroglial molecules, transketolase, 2',3'-cyclic-nucleotide 3'-phosphodiesterase type I, collapsin response mediator protein 2, and tubulin beta 4. Interestingly 50% of MuS IgG recognized transketolase, which was mostly localized on oligodendrocytes in human white matter from normal and MuS samples. IgG autoreactivity to cytoskeletal proteins (radixin, sirtuin 2, and actin-interacting protein 1) was prevalent in secondary progressive MuS patients. Among the proteins recognized by serum IgG, almost all MuS patients specifically recognized a restricted number of neuronal/cytoskeletal proteins, whereas 2',3'-cyclic-nucleotide 3'-phosphodiesterase type I was the oligodendroglial antigen most frequently recognized (44%) by MuS seric IgG. Our immunomics approach shed new light on the autoimmune repertoire present in MuS patients revealing novel oligodendroglial and/or neuronal putative autoantigens with potential important pathogenic and diagnostic implications.
authors.affiliation: Department of Neurological Sciences and Vision, University of Verona, 37134 Verona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cianti
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gini
authors.forename: Silvia
authors.initials: S
authors.lastname: Marconi
authors.forename: Laura
authors.initials: L
authors.lastname: Bianchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Armini
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.forename: Francesca
authors.initials: F
authors.lastname: Locatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Paoletti
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.forename: Luca
authors.initials: L
authors.lastname: Bini
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonetti
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000276:immunology*; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D003710:Demography; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D021381:Protein Transport; D014174:Transketolase / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007527:Isoenzymes; D014174:Transketolase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases