Expression of myxovirus-resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis.

Autor: Soponkanaporn S; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK.; Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Deakin CT; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK., Schutz PW; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK.; Division of Neuropathology, Vancouver General Hospital, Vancouver, BC, Canada.; Department of Pathology, University of British Columbia, Vancouver, BC, Canada., Marshall LR; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK., Yasin SA; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK., Johnson CM; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK., Sag E; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK.; Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey., Tansley SL; Department of Pharmacy and Pharmacology, University of Bath, Bath, UK., McHugh NJ; Department of Pharmacy and Pharmacology, University of Bath, Bath, UK., Wedderburn LR; Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London, UK.; Rheumatology Unit, Great Ormond Street Hospital for Children, London, UK.; NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children, NHS Foundation Trust and University College London, London, UK.; Arthritis Research UK Centre for Adolescent Rheumatology at UCL, UCLH and GOSH, London, UK., Jacques TS; Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Jazyk: angličtina
Zdroj: Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2019 Jun; Vol. 45 (4), pp. 410-420. Date of Electronic Publication: 2018 Jun 04.
DOI: 10.1111/nan.12498
Abstrakt: Aims: To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients.
Methods: 103 patients (median aged 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status.
Results: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti-melanoma differentiation-associated gene 5 positive patients had no or weak MxA expression.
Conclusions: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status.
(© 2018 The Authors Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)
Databáze: MEDLINE
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