title: Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.|Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK.
authors.forename: J B
authors.identifier: http://orcid.org/0000-0002-9230-4137
authors.initials: JB
authors.lastname: Lilleker
authors.affiliation: Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Rietveld
authors.affiliation: 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.
authors.forename: S R
authors.initials: SR
authors.lastname: Pye
authors.affiliation: Department of Internal Medicine and Clinical Immunology, La Pitié-Salpêtrière Hospital, AP-HP, INSERM U974, UPMC, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Mariampillai
authors.affiliation: Department of Internal Medicine and Clinical Immunology, La Pitié-Salpêtrière Hospital, AP-HP, INSERM U974, UPMC, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Benveniste
authors.affiliation: Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M T J
authors.initials: MT
authors.lastname: Peeters
authors.affiliation: Department of Neurology, Royal Victoria Hospitals, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
authors.forename: J A L
authors.initials: JA
authors.lastname: Miller
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.|Centre for Rheumatology Research, University College London, London, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Machado
authors.affiliation: MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Parton
authors.affiliation: Unit of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K R
authors.initials: KR
authors.lastname: Gheorghe
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: U A
authors.initials: UA
authors.lastname: Badrising
authors.affiliation: Unit of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I E
authors.initials: IE
authors.lastname: Lundberg
authors.affiliation: Peripheral Nervous System, Muscle and ALS Department, Université Côté Azure (UCA), Nice University Hospital, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Sacconi
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: M K
authors.initials: MK
authors.lastname: Herbert
authors.affiliation: Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.affiliation: The Walton Centre NHS Foundation Trust, Fazakerley, Liverpool, UK.
authors.forename: B R F
authors.initials: BR
authors.lastname: Lecky
authors.affiliation: Department of Neurology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: C
authors.initials: C
authors.lastname: Brierley
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hilton-Jones
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Lamb
authors.affiliation: Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Roberts
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.|MRC-ARUK Institute for Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.|Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: R G
authors.initials: RG
authors.lastname: Cooper
authors.affiliation: Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: C G J
authors.initials: CG
authors.lastname: Saris
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: G J M
authors.initials: GJ
authors.lastname: Pruijn
authors.affiliation: 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.|Rheumatology Department, Salford Royal NHS Foundation Trust, Salford, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: H
authors.initials: H
authors.lastname: Chinoy
authors.affiliation: Department of Neurology, Center for Neuroscience Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: B G M
authors.initials: BG
authors.lastname: van Engelen
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology*; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003600:Cytosol; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000473:pathology*; D018908:Muscle Weakness / Q000209:etiology; D018979:Myositis, Inclusion Body / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012656:Self-Help Devices / Q000706:statistics & numerical data; D015996:Survival Rate; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D003576:Electron Transport Complex IV; D015720:5'-Nucleotidase; C552626:NT5C1A protein, human
keywords: Autoantibodies; Dermatomyositis; Polymyositis