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Autoantibodies to cytosolic 5′‐nucleotidase 1A in inclusion body myositis
Author(s) -
Pluk Helma,
Hoeve Bas J. A.,
Dooren Sander H. J.,
StammenVogelzangs Judith,
Heijden Annemarie,
Schelhaas Helenius J.,
Verbeek Marcel M.,
Badrising Umesh A.,
Arnardottir Snjolaug,
Gheorghe Karina,
Lundberg Ingrid E.,
Boelens Wilbert C.,
Engelen Baziel G.,
Pruijn Ger J. M.
Publication year - 2013
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23822
Subject(s) - autoantibody , polymyositis , dermatomyositis , myositis , antigen , inclusion body myositis , epitope , microbiology and biotechnology , skeletal muscle , biology , 5' nucleotidase , antibody , immunology , medicine , pathology , biochemistry , endocrinology , enzyme
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 M r 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