Autoantibodies to cytosolic 5′-nucleotidase 1A in inclusion body myositis

Objective Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy characterized by both degenerative and autoimmune features. In contrast to other inflammatory myopathies, myositis‐specific autoantibodies had not been found in sIBM patients until recently. We used human skeletal muscle e...

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Bibliographic Details
Published in:	Annals of neurology 2013-03, Vol.73 (3), p.397-407
Main Authors:	Pluk, Helma, van Hoeve, Bas J. A., van Dooren, Sander H. J., Stammen-Vogelzangs, Judith, van der Heijden, Annemarie, Schelhaas, Helenius J., Verbeek, Marcel M., Badrising, Umesh A., Arnardottir, Snjolaug, Gheorghe, Karina, Lundberg, Ingrid E., Boelens, Wilbert C., van Engelen, Baziel G., Pruijn, Ger J. M.
Format:	Article
Language:	eng
Subjects:	5'-Nucleotidase - immunology Animals Autoantibodies - blood Cells, Cultured Female Humans Immunoprecipitation Male Mass Spectrometry Medicin och hälsovetenskap Mice Molecular Weight Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular system Musculoskeletal system Myositis, Inclusion Body - blood Myositis, Inclusion Body - immunology Myositis, Inclusion Body - pathology Proteins Radioimmunoprecipitation Assay
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Summary:	Objective Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy characterized by both degenerative and autoimmune features. In contrast to other inflammatory myopathies, myositis‐specific autoantibodies had not been found in sIBM patients until recently. We used human skeletal muscle extracts as a source of antigens to detect autoantibodies in sIBM and to characterize the corresponding antigen. Methods Autoantibodies to skeletal muscle antigens were detected by immunoblotting. The target antigen was immunoaffinity‐purified from skeletal muscle extracts and characterized by mass spectrometry. A cDNA encoding this protein was cloned and expressed in vitro, and its recognition by patient sera was analyzed in an immunoprecipitation assay. Epitopes were mapped using microarrays of overlapping peptides. Results An Mr 44,000 polypeptide (Mup44) was frequently targeted by sIBM autoantibodies. The target protein was purified, and subsequent mass spectrometry analysis revealed that Mup44 is the cytosolic 5′‐nucleotidase 1A (cN1A). By immunoprecipitation of recombinant cN1A, high concentrations of anti‐Mup44 autoantibodies were detected in 33% of sIBM patient sera, whereas their prevalence in dermatomyositis, polymyositis, and other neuromuscular disorders appeared to be rare (4.2%, 4.5%, and 3.2%, respectively). Low concentrations of anti‐Mup44 antibodies were found in myositis as well as other neuromuscular disorders, but not in healthy controls. Three major autoepitope regions of cN1A were mapped by using microarrays containing a set of overlapping peptides covering the complete cN1A amino acid sequence. Interpretation Anti‐Mup44 autoantibodies, which are targeted to cN1A, represent the first serological biomarker for sIBM and may facilitate the diagnosis of this type of myositis. ANN NEUROL 2013;73:397–407
ISSN:	0364-5134 1531-8249 1531-8249