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Originally published In Press as doi:10.1074/mcp.M700277-MCP200 on July 31, 2008.
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Molecular & Cellular Proteomics 7:2337-2349, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.


Research

Transketolase and 2',3'-Cyclic-nucleotide 3'-Phosphodiesterase Type I Isoforms Are Specifically Recognized by IgG Autoantibodies in Multiple Sclerosis Patients *,S

Laura Lovato{ddagger}, Riccardo Cianti§, Beatrice Gini{ddagger}, Silvia Marconi{ddagger}, Laura Bianchi§, Alessandro Armini§, Elena Anghileri{ddagger}, Francesca Locatelli, Francesco Paoletti||, Diego Franciotta**, Luca Bini§ and Bruno Bonetti{ddagger},{ddagger}{ddagger}

From the Departments of {ddagger} Neurological Sciences and Vision, Section of Neurology, and Hygiene and Public Health, Section of Epidemiology and Medical Statistics, University of Verona, 37134 Verona, Italy, § Molecular Biology, University of Siena, 53100 Siena, Italy, || Experimental Pathology and Oncology, University of Firenze, 50100 Firenze, Italy, and ** Laboratory of Neuroimmunology, Neurological Institute "C. Mondino," University of Pavia, 27100 Pavia, Italy

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 β4. 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.


{ddagger}{ddagger} To whom correspondence should be addressed: Section of Neurology, Dept. of Neurological Sciences and Vision, University of Verona, Policlinico "G. B. Rossi," P. le L. A. Scuro 10, 37134 Verona, Italy. Tel.: 39-045-8124694; Fax: 39-045-585933; E-mail: bruno.bonetti{at}univr.it


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