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Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis
  1. J B Lilleker1,2,
  2. A Rietveld3,
  3. S R Pye1,
  4. K Mariampillai4,
  5. O Benveniste4,
  6. M T J Peeters3,
  7. J A L Miller5,
  8. M G Hanna6,
  9. P M Machado6,7,
  10. M J Parton6,
  11. K R Gheorghe8,
  12. U A Badrising9,
  13. I E Lundberg8,
  14. S Sacconi10,
  15. M K Herbert11,
  16. N J McHugh12,
  17. B R F Lecky13,
  18. C Brierley14,
  19. D Hilton-Jones15,
  20. J A Lamb16,
  21. M E Roberts2,
  22. R G Cooper16,17,18,
  23. C G J Saris3,
  24. G J M Pruijn11,
  25. H Chinoy1,18,19,
  26. B G M van Engelen3
  27. On behalf of all UKMYONET contributors
  1. 1Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  2. 2Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK
  3. 3Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
  4. 4Department of Internal Medicine and Clinical Immunology, La Pitié-Salpêtrière Hospital, AP-HP, INSERM U974, UPMC, Paris, France
  5. 5Department of Neurology, Royal Victoria Hospitals, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
  6. 6MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK
  7. 7Centre for Rheumatology Research, University College London, London, UK
  8. 8Unit of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  9. 9Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
  10. 10Peripheral Nervous System, Muscle and ALS Department, Université Côté Azure (UCA), Nice University Hospital, Nice, France
  11. 11Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
  12. 12Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
  13. 13The Walton Centre NHS Foundation Trust, Fazakerley, Liverpool, UK
  14. 14Department of Neurology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  15. 15Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK
  16. 16Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK
  17. 17MRC-ARUK Institute for Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
  18. 18Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, UK
  19. 19NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  1. Correspondence to Dr J B Lilleker, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M13 9PT, UK; james.lilleker{at}


Objectives Autoantibodies directed against cytosolic 5′-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5′-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.

Materials and methods Data from various European inclusion body myositis registries were pooled. Anticytosolic 5′-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.

Results Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5′-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.

Interpretation Differences were observed in clinical and histopathological features between anticytosolic 5′-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5′-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

  • Autoantibodies
  • Dermatomyositis
  • Polymyositis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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  • Handling editor Tore K Kvien

  • JBL and AR are joint first authors.

    HC and BGMvE are joint last authors.

  • Twitter Follow Hector Chinoy at @drhectorchinoy

  • Contributors Initiation and design of this research: Non-UK––CGJS, BGMvE and GJMP; UK––RGC, HC and JAL. Clinical data collection and processing: AR, JBL, MTJP, KM and KRG. Facilitation of clinical data collection, establishment of the cohorts, contribution of cases: UAB, OB, IEL, SS, HC, RGC, JALM, MGH, PMM, MJP, BRFL, CB, DH-J and MER. Establishment of the antibody detection method and laboratory analysis: MKH, BGMvE and GJMP. Statistical analysis: JBL and SRP. Draft manuscript preparation: AR and JBL. All authors were involved with the review of the manuscript and approved the final version.

  • Funding This study was supported in part by: the Prinses Beatrix Spierfonds (W.OR 12–15); Myositis UK; Arthritis Research UK (18474); Association Française Contre Les Myopathies; The European Union Sixth Framework Programme (project AutoCure; LSH-018661); European Science Foundation in the framework of the Research Networking Programme European Myositis Network; The Swedish Research Council. PMM was supported by a National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration Fellowship. This report includes independent research supported by the NIHR Biomedical Research Unit cFunding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The UKMYONET project is supported by the Manchester Academic Health Sciences Centre (MAHSC).

  • Competing interests GJMP and BGMvE are inventors of a patent (EP20120740236) licensed to Euroimmun, and GJMP receives financial support from Euroimmun for his research programme. Leiden University Medical Center receives financial compensation from Novartis for the BYM338 clinical trials in IBM in which UAB is the principal investigator.

  • Ethics approval Local ethics committee of each of the participating centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.