title: Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases.
abstract: OBJECTIVE
  The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls.
  
  
  METHODS
  Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs.
  
  
  RESULTS
  Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%).
  
  
  CONCLUSIONS
  In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.
authors.affiliation: Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Herbert
authors.affiliation: Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Stammen-Vogelzangs
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Rietveld
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.affiliation: Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
authors.forename: Hector
authors.initials: H
authors.lastname: Chinoy
authors.affiliation: Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK.
authors.forename: Janine A
authors.initials: JA
authors.lastname: Lamb
authors.affiliation: Faculty of Health & Life Sciences, MRC/ARUK Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cooper
authors.affiliation: Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Umesh A
authors.initials: UA
authors.lastname: Badrising
authors.affiliation: Department of Neurology, Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jan L
authors.initials: JL
authors.lastname: De Bleecker
authors.affiliation: MRC Centre for Neuromuscular Diseases, University College London, London, UK.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Machado
authors.affiliation: MRC Centre for Neuromuscular Diseases, University College London, London, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Plestilova
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic.
authors.forename: Jiri
authors.identifier: http://orcid.org/0000-0002-0851-0713
authors.initials: J
authors.lastname: Vencovsky
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Baziel G
authors.initials: BG
authors.lastname: van Engelen
authors.affiliation: Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology*; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D016022:Case-Control Studies; D003882:Dermatomyositis / Q000175:diagnosis / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology; D018979:Myositis, Inclusion Body / Q000175:diagnosis / Q000276:immunology*; D009468:Neuromuscular Diseases / Q000276:immunology; D017285:Polymyositis / Q000175:diagnosis / Q000276:immunology; D012372:ROC Curve; D012595:Scleroderma, Systemic / Q000276:immunology; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015720:5'-Nucleotidase; C552626:NT5C1A protein, human
keywords: Autoantibodies; Autoimmune Diseases; Dermatomyositis; Polymyositis