Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

J B Lilleker^{1

2}, A Rietveld³, S R Pye¹, K Mariampillai⁴, O Benveniste⁴, M T J Peeters³, J A L Miller⁵, M G Hanna⁶, P M Machado^{6

7}, M J Parton⁶, K R Gheorghe⁸, U A Badrising⁹, I E Lundberg⁸, S Sacconi¹⁰, M K Herbert¹¹, N J McHugh¹², B R F Lecky¹³, C Brierley¹⁴, D Hilton-Jones¹⁵, J A Lamb¹⁶, M E Roberts², R G Cooper^{16

17

18}, C G J Saris³, G J M Pruijn¹¹, H Chinoy^{1

18

19}, B G M van Engelen³; all UKMYONET contributors

Affiliations

¹ 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, UK.
² Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK.
³ Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Department of Internal Medicine and Clinical Immunology, La Pitié-Salpêtrière Hospital, AP-HP, INSERM U974, UPMC, Paris, France.
⁵ Department of Neurology, Royal Victoria Hospitals, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
⁶ MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
⁷ Centre for Rheumatology Research, University College London, London, UK.
⁸ Unit of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Peripheral Nervous System, Muscle and ALS Department, Université Côté Azure (UCA), Nice University Hospital, Nice, France.
¹¹ Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
¹² Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
¹³ The Walton Centre NHS Foundation Trust, Fazakerley, Liverpool, UK.
¹⁴ Department of Neurology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁵ Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK.
¹⁶ Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
¹⁷ MRC-ARUK Institute for Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
¹⁸ Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, UK.
¹⁹ NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

PMID: 28122761
PMCID: PMC5530338
DOI: 10.1136/annrheumdis-2016-210282

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

J B Lilleker et al. Ann Rheum Dis. 2017 May.

. 2017 May;76(5):862-868.

doi: 10.1136/annrheumdis-2016-210282. Epub 2017 Jan 25.

Authors

Affiliations

¹ 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, UK.
² Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK.
³ Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Department of Internal Medicine and Clinical Immunology, La Pitié-Salpêtrière Hospital, AP-HP, INSERM U974, UPMC, Paris, France.
⁵ Department of Neurology, Royal Victoria Hospitals, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
⁶ MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
⁷ Centre for Rheumatology Research, University College London, London, UK.
⁸ Unit of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Peripheral Nervous System, Muscle and ALS Department, Université Côté Azure (UCA), Nice University Hospital, Nice, France.
¹¹ Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
¹² Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
¹³ The Walton Centre NHS Foundation Trust, Fazakerley, Liverpool, UK.
¹⁴ Department of Neurology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁵ Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK.
¹⁶ Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
¹⁷ MRC-ARUK Institute for Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
¹⁸ Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, UK.
¹⁹ NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

PMID: 28122761
PMCID: PMC5530338
DOI: 10.1136/annrheumdis-2016-210282

Abstract

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.

Keywords: Autoantibodies; Dermatomyositis; Polymyositis.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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Conflict of interest statement

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.

Figures

**Figure 1**
Kaplan-Meier survival curves stratified by anti-cN-1A antibody status. X-axis truncated at 25 years from disease onset.

See this image and copyright information in PMC

References

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Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

Affiliations

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials