title: Muscle Biopsy Findings in Combination With Myositis-Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis.
abstract: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM.
  
  
  
  Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations.
  
  
  
  Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013).
  
  
  
  Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.
authors.affiliation: University College London, London, UK.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Deakin
authors.affiliation: University College London, London, UK.
authors.forename: Shireena A
authors.initials: SA
authors.lastname: Yasin
authors.affiliation: University College London, London, UK.
authors.forename: Stefania
authors.initials: S
authors.lastname: Simou
authors.affiliation: University College London, London, UK.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Arnold
authors.affiliation: University of Bath, Bath, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tansley
authors.affiliation: University of Bath, Bath, UK.
authors.forename: Zoe E
authors.initials: ZE
authors.lastname: Betteridge
authors.affiliation: University of Bath, Bath, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: McHugh
authors.affiliation: University College London, London, UK.
authors.forename: Hemlata
authors.initials: H
authors.lastname: Varsani
authors.affiliation: University College London, London, UK.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.affiliation: University College London, London, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Clarissa A
authors.initials: CA
authors.lastname: Pilkington
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust and University College London, London, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Nistala
authors.affiliation: University College London, Great Ormond Street Hospital for Children NHS Foundation Trust, and University College London Hospitals, London, UK. l.wedderburn@ucl.ac.uk.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D026942:DNA Topoisomerases / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D003882:Dermatomyositis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000072640:Interferon-Induced Helicase, IFIH1 / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D016017:Odds Ratio; D011379:Prognosis; D065840:Protective Factors; D052097:Quadriceps Muscle / Q000473:pathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D018271:Signal Recognition Particle / Q000276:immunology; D013914:Threonine-tRNA Ligase / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D006113:United Kingdom
chemical_list: D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; C045760:Mi-2 antibodies; D018271:Signal Recognition Particle; C511956:TRIM33 protein, human; D014157:Transcription Factors; C087950:nuclear matrix protein 2; C452815:IFIH1 protein, human; D000072640:Interferon-Induced Helicase, IFIH1; D026942:DNA Topoisomerases; D013914:Threonine-tRNA Ligase; D008727:Methotrexate