title: Autoantibodies to cytosolic 5'-nucleotidase 1A in inclusion body myositis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biomolecular Chemistry, Institute for Molecules and Materials and Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
authors: Helma
authors: H
authors: Pluk
authors: Bas J A
authors: BJ
authors: van Hoeve
authors: Sander H J
authors: SH
authors: van Dooren
authors: Judith
authors: J
authors: Stammen-Vogelzangs
authors: Annemarie
authors: A
authors: van der Heijden
authors: Helenius J
authors: HJ
authors: Schelhaas
authors: Marcel M
authors: MM
authors: Verbeek
authors: Umesh A
authors: UA
authors: Badrising
authors: Snjolaug
authors: S
authors: Arnardottir
authors: Karina
authors: K
authors: Gheorghe
authors: Ingrid E
authors: IE
authors: Lundberg
authors: Wilbert C
authors: WC
authors: Boelens
authors: Baziel G
authors: BG
authors: van Engelen
authors: Ger J M
authors: GJ
authors: Pruijn
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015531:Radioimmunoprecipitation Assay
chemical_list: D001323:Autoantibodies; D015720:5'-Nucleotidase