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Disease specificity of autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases
  1. Megan K Herbert1,
  2. Judith Stammen-Vogelzangs1,
  3. Marcel M Verbeek2,3,
  4. Anke Rietveld2,
  5. Ingrid E Lundberg4,
  6. Hector Chinoy5,
  7. Janine A Lamb6,
  8. Robert G Cooper7,
  9. Mark Roberts8,
  10. Umesh A Badrising9,
  11. Jan L De Bleecker10,
  12. Pedro M Machado11,
  13. Michael G Hanna11,
  14. Lenka Plestilova12,
  15. Jiri Vencovsky12,
  16. Baziel G van Engelen2,
  17. Ger J M Pruijn1
  1. 1Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
  2. 2Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
  3. 3Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
  4. 4Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden
  5. 5Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  6. 6Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK
  7. 7Faculty of Health & Life Sciences, MRC/ARUK Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
  8. 8Salford Royal NHS Foundation Trust, Manchester, UK
  9. 9Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
  10. 10Department of Neurology, Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium
  11. 11MRC Centre for Neuromuscular Diseases, University College London, London, UK
  12. 12Department of Rheumatology, First Faculty of Medicine, Institute of Rheumatology, Charles University, Prague, Czech Republic
  1. Correspondence to Professor Ger J M Pruijn, Department of Biomolecular Chemistry 284, Radboud University Nijmegen, PO Box 9101, Nijmegen NL-6500 HB, The Netherlands; G.Pruijn{at}ncmls.ru.nl

Abstract

Objectives 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.

  • Autoantibodies
  • Autoimmune Diseases
  • Dermatomyositis
  • Polymyositis

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