title: Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset.
abstract: OBJECTIVE
  Calcinosis is a major cause of morbidity in JDM and has previously been linked to anti-NXP2 autoantibodies, younger age at disease onset and more persistent disease activity. This study aimed to investigate the clinical associations of anti-NXP2 autoantibodies in patients with JDM stratified by age at disease onset.
  
  
  METHODS
  A total of 285 patients with samples and clinical data were recruited via the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-NXP2 was determined by both immunoprecipitation and ELISA. Logistic regression analysis was performed to assess the age-dependent relationship between anti-NXP2 and the development of calcinosis and disease activity measures.
  
  
  RESULTS
  We identified anti-NXP2 autoantibodies in 56 patients (20%). While in all patients younger age at disease onset was associated with an increased risk of calcinosis and this relationship was nearly linear, anti-NXP2 autoantibodies substantially increased the risk of calcinosis across all ages (P = 0.025) and were detectable prior to calcinosis development. Children with anti-NXP2 autoantibodies had a greater degree of weakness (median lowest ever Childhood Myositis Assessment Score 29.6 vs 42) and were less likely to be in remission at 2 years post-diagnosis. No difference in disease activity was seen 4 years post-diagnosis.
  
  
  CONCLUSIONS
  Children diagnosed at a young age have a high risk of calcinosis regardless of autoantibody status. However, the presence of anti-NXP2 autoantibodies substantially increases the risk of calcinosis across all ages and is associated with disease severity.
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tansley
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Zoe E
authors.initials: ZE
authors.lastname: Betteridge
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Shaddick
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Harsha
authors.initials: H
authors.lastname: Gunawardena
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK. Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Arnold
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK. Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.affiliation: Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Department of Pharmacy and Pharmacology, University of Bath, Department of Mathematical Sciences, University of Bath, Bath, Department of Rheumatology, Southmead Hospital, North Bristol NHS Trust, Bristol, Rheumatology Unit, University College London Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital and Great Ormond Street Hospital, London, UK. Neil.McHugh@rnhrd.nhs.uk.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: McHugh
mesh_terms: D000251:Adenosine Triphosphatases / Q000276:immunology*; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000209:etiology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000276:immunology*; D003882:Dermatomyositis / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000209:etiology / Q000276:immunology; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C551732:MORC3 protein, human
keywords: age; autoantibody; calcinosis; juvenile dermatomyositis