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Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis
  1. Richard M Yeker1,
  2. Iago Pinal-Fernandez1,2,
  3. Takayuki Kishi3,
  4. Katherine Pak1,
  5. Ira N Targoff4,5,
  6. Frederick W Miller3,
  7. Lisa G Rider3,
  8. Andrew L Mammen1,2,6
  9. for the Childhood Myositis Heterogeneity Collaborative Study Group
    1. 1 Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA
    2. 2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    3. 3 Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, Bethesda, Maryland, USA
    4. 4 US Department of Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
    5. 5 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
    6. 6 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    1. Correspondence to Dr Andrew L Mammen, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA; andrew.mammen{at}


    Objectives Autoantibodies recognising cytosolic 5′-nucleotidase 1A (NT5C1A) are found in adult patients with myositis and other autoimmune diseases. They are especially prevalent in adults with inclusion body myositis (IBM), in which they are associated with more severe weakness and higher mortality. This study was undertaken to define the prevalence and clinical features associated with anti-NT5C1A autoantibodies in juvenile myositis.

    Methods We screened sera from 380 patients with juvenile myositis, 30 patients with juvenile idiopathic arthritis (JIA) and 92 healthy control children for anti-NT5C1A autoantibodies. Clinical characteristics were compared between patients with myositis with and without anti-NT5C1A autoantibodies.

    Results Anti-NT5C1A autoantibodies were present in 102 of 380 (27%) patients with juvenile myositis and in 11 of 92 (12%) healthy control children (P=0.002) and 27% of children with JIA (P=0.05 vs controls). Sera of 83 of 307 (27%) patients with juvenile dermatomyositis and 16 of 46 (35%) patients with juvenile overlap myositis were anti-NT5C1A autoantibody-positive (P<0.01 vs healthy controls for each), but sera of only 3 of 27 (11%) patients with juvenile polymyositis were anti-NT5C1A-positive. Patients with juvenile myositis with and without anti-NT5C1A autoantibodies had similar clinical phenotypes. However, patients with anti-NT5C1A autoantibody-positive myositis had greater pulmonary symptoms at diagnosis (P=0.005), more frequent hospitalisations (P=0.01) and required a larger number of medications (P<0.001).

    Conclusion Anti-NT5C1A autoantibodies are present in more than one-quarter of children with juvenile myositis and JIA compared with only 12% of healthy children, suggesting they are myositis-associated in children. As in adults with IBM, patients with juvenile myositis with anti-NT5C1A autoantibodies have more severe disease.

    • dermatomyositis
    • polymyositis
    • autoantibodies
    • autoimmunity
    • juvenile idiopathic arthritis

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    • LGR and ALM contributed equally.

    • RMY and IP-F contributed equally.

    • Handling editor Josef S Smolen

    • Contributors All authors: involved in drafting the article or revising it critically for important intellectual content and approved the final manuscript to be submitted and agreed to be accountable for all aspects of the work. RMY, IP-F, FWM, LGR and ALM: conception and design of the study. RMY, IP-F, TK, KP, INT and LGR: acquisition of data. RMY, IP-F, TK, INT, FWM, LGR and ALM: analysis and interpretation of data.

    • Funding This work was supported in part by the National Institute of Environmental Health Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. IP-F and TK were supported by research fellowships from The Myositis Association.

    • Disclaimer IT is a consultant to the Oklahoma Medical Research Foundation Clinical Immunology Laboratory regarding myositis autoantibody testing.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval All subjects were enrolled in investigational review board-approved natural history studies from 1990 to 2016. The parents of the pediatric patients in this study signed a consent form approved by the Institutional Review Board at the National Institutes of Health.

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

    • Data sharing statement No unpublished data related to this study are publicly available.

    • Collaborators Daniel A Albert, Bita Arabshahi, Imelda M Balboni, John F Bohnsack, Michael S Borzy, Suzanne L Bowyer (postmortem), Chun Peng T Chao, Randy Q Cron, Marietta M DeGuzman, Ellen A Goldmuntz, Thomas A Griffin, William Hannan, Melissa Hawkins-Holt, J Roger Hollister, Russell J Hopp, Jerry C Jacobs (postmortem), Anna Jansen, Olcay Y Jones, Lawrence K Jung, Ankur Kamdar, Steven J Klein, Bianca A Lang, Katherine L Madson, Paul L McCarthy, Gulnara Mamyrova, Stephen R Mitchell, Frederick T Murphy, Kabita Nanda, Terrance P O’Hanlon, Elif A Oral, Lauren M Pachman, Murray H Passo, Maria D Perez, Donald A Person, Linda I Ray, Robert M Rennebohm, Rafael F Rivas-Chacon, Tova Ronis, Adam Schiffenbauer, Bracha Shaham, David D Sherry, Sara H Sinal, Abigail Smukler, Sangeeta H Sule, Scott A Vogelgesang, Jennifer C Wargula and Patience H White.