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.
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Handling editor Tore K Kvien
JBL and AR are joint first authors.
HC and BGMvE are joint last authors.
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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.
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