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

S Soponkanaporn,C T Deakin,S L Tansley,N J Mchugh,T S Jacques,L R Wedderburn,C M Johnson,S A Yasin,E Sag,P W Schutz,L R Marshall

doi:10.1111/nan.12498

Abstract

AimsTo 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.Methods103 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.ResultsExpression 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.ConclusionsThis 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.

Highlights

Juvenile dermatomyositis (JDM) is a rare chronic inflammatory myopathy of childhood, with primary symptoms including symmetrical, proximal muscle weakness and typical skin rashes including Gottron’s papules and heliotrope rash
The sample size in the previous study was limited, there was about 90% of JDM patients who had positive Myxovirus-resistance protein A (MxA) staining in muscle fibres
The percentages of positive MxA staining in JDM in the previous study is higher than in this study which was about 61% could be explained by the different classification criteria for including of participants and different MxA clones for IHC detection

Summary

Introduction

Juvenile dermatomyositis (JDM) is a rare chronic inflammatory myopathy of childhood, with primary symptoms including symmetrical, proximal muscle weakness and typical skin rashes including Gottron’s papules and heliotrope rash. This study aimed to evaluate the relationship between expression of MxA protein on muscle biopsies by immunohistochemistry (IHC) and disease activity in JDM patients. We included patients with MSA and nodetectable autoantibodies during the analyses in order to assess the relationships between MSA status and MxA expression on JDM muscle specimens. This study included clinical data and muscle biopsy samples from 103 patients with definite or probable JDM [16,17] who were already recruited to the Juvenile Dermatomyositis Cohort and Biomarker Study. The expression of MxA in muscle fibres was scored semi-quantitatively by two independent investigators including a senior neurohistopathologist who were blinded to patients’ clinical features and laboratory data. Differences in CMAS scores, MMT8, PGA and serum levels of muscle enzymes between different MxA scoring data were tested by Kruskal– Wallis analysis of variance.

Results

Discussion

Conflict of interest