Expression of Myxovirus-resistance Protein A

A Possible Marker of Muscle Disease Activity and Autoantibody Specificities in Juvenile Dermatomyositis

Sirisucha Soponkanaporn, Claire T Deakin, Peter W Schutz, Lucy R Marshall, Shireena A Yasin, Cerise M Johnson, Erdal Sag, Sarah L Tansley, Neil J McHugh, Lucy R Wedderburn, Thomas S Jacques

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Abstract

AIMS: To evaluate the relationship between expression of Myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in 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, IQR 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 NXP-2 autoantibodies had strong MxA expression whereas anti-MDA5 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.

Original languageEnglish
Pages (from-to)410-420
JournalNeuropathology and Applied Neurobiology
Volume45
Issue number4
Early online date16 May 2018
DOIs
Publication statusPublished - 30 Jun 2019

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Myxovirus Resistance Proteins
Staphylococcal Protein A
Autoantibodies
Myositis
Muscles
Juvenile dermatomyositis
Biopsy
Muscle Proteins
Muscular Diseases

Keywords

  • Journal Article

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Expression of Myxovirus-resistance Protein A : A Possible Marker of Muscle Disease Activity and Autoantibody Specificities in Juvenile Dermatomyositis. / Soponkanaporn, Sirisucha; Deakin, Claire T; Schutz, Peter W; Marshall, Lucy R; Yasin, Shireena A; Johnson, Cerise M; Sag, Erdal; Tansley, Sarah L; McHugh, Neil J; Wedderburn, Lucy R; Jacques, Thomas S.

In: Neuropathology and Applied Neurobiology, Vol. 45, No. 4, 30.06.2019, p. 410-420.

Research output: Contribution to journalArticle

Soponkanaporn, S, Deakin, CT, Schutz, PW, Marshall, LR, Yasin, SA, Johnson, CM, Sag, E, Tansley, SL, McHugh, NJ, Wedderburn, LR & Jacques, TS 2019, 'Expression of Myxovirus-resistance Protein A: A Possible Marker of Muscle Disease Activity and Autoantibody Specificities in Juvenile Dermatomyositis', Neuropathology and Applied Neurobiology, vol. 45, no. 4, pp. 410-420. https://doi.org/10.1111/nan.12498
Soponkanaporn, Sirisucha ; Deakin, Claire T ; Schutz, Peter W ; Marshall, Lucy R ; Yasin, Shireena A ; Johnson, Cerise M ; Sag, Erdal ; Tansley, Sarah L ; McHugh, Neil J ; Wedderburn, Lucy R ; Jacques, Thomas S. / Expression of Myxovirus-resistance Protein A : A Possible Marker of Muscle Disease Activity and Autoantibody Specificities in Juvenile Dermatomyositis. In: Neuropathology and Applied Neurobiology. 2019 ; Vol. 45, No. 4. pp. 410-420.
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abstract = "AIMS: To evaluate the relationship between expression of Myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in 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, IQR 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 NXP-2 autoantibodies had strong MxA expression whereas anti-MDA5 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.",
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TY - JOUR

T1 - Expression of Myxovirus-resistance Protein A

T2 - A Possible Marker of Muscle Disease Activity and Autoantibody Specificities in Juvenile Dermatomyositis

AU - Soponkanaporn, Sirisucha

AU - Deakin, Claire T

AU - Schutz, Peter W

AU - Marshall, Lucy R

AU - Yasin, Shireena A

AU - Johnson, Cerise M

AU - Sag, Erdal

AU - Tansley, Sarah L

AU - McHugh, Neil J

AU - Wedderburn, Lucy R

AU - Jacques, Thomas S

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/6/30

Y1 - 2019/6/30

N2 - AIMS: To evaluate the relationship between expression of Myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in 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, IQR 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 NXP-2 autoantibodies had strong MxA expression whereas anti-MDA5 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.

AB - AIMS: To evaluate the relationship between expression of Myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in 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, IQR 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 NXP-2 autoantibodies had strong MxA expression whereas anti-MDA5 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.

KW - Journal Article

U2 - 10.1111/nan.12498

DO - 10.1111/nan.12498

M3 - Article

VL - 45

SP - 410

EP - 420

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 4

ER -