Background/Purpose:

Juvenile dermatomyositis (JDM) is a chronic autoimmune myopathy characterized by proximal muscle weakness and typical skin rashes. Type I interferon (IFN) gene expression in blood has been shown to correlate with muscle involvement in adult and juvenile dermatomyositis. Myxovirus-resistance protein A (MxA), a type I IFN-induced protein, is specifically regulated by type I IFN pathway. Since muscle is the major target of inflammation, the presence of MxA protein in muscles could be of greater relevance to direct mechanisms of tissue injury. This study aims to examine whether MxA protein expression in muscles correlates with disease activity in JDM.

Methods:

103 patients enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS) had muscle biopsies available, which were stained for MxA by immunohistochemistry. The expression of MxA in muscle fibres was scored semi-quantitatively. Scores range from 0 to 3 (0 = no MxA staining; 1 = weak; 2 = moderate; 3 = strong). Clinical and laboratory data at initial presentation including Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing of Eight Muscles (MMT8), physician’s global assessment (PGA) and muscle enzymes were collected. Kruskal-Wallis ANOVA with Bonferroni’s correction were tested to examine differences of MxA scoring data in muscle disease activity. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity. The strength of the association was described by the standardised coefficient (β).

Results:

The median age at disease onset was 6.3 years and median duration from disease onset to muscle biopsy was 3.8 months. About 9% of patients had received corticosteroids at the time of biopsy. MxA expression was identified in 63 of 103 patients, with 57% of those showing strong MxA expression on myofibres. The distribution of MxA expression was observed in both perifascicular (46%) and scattered (53%) patterns. Comparing patients with varying MxA scores, there were no significant differences in age at onset, gender, and clinical features at first presentation, such as, the presence of calcinosis, nail fold capillary changes and PGA. There were statistical differences in duration from disease onset to muscle biopsy (p = 0.046), CMAS (p = 0.002) and MMT8 (p = 0.026). CMAS and MMT8 were significantly lower in the group of patients with strong MXA expression. From post hoc analysis, there were significant differences in CMAS between patients with scores of 0 and 2 (p = 0.044), and scores of 0 and 3 (p = 0.001). Also, MMT8 in patients with scores of 0 and 3 were statistically significantly different (p = 0.013). Regression analysis confirmed that expression of MxA was significantly associated with CMAS (β = -0.433) and MMT8 (β = -0.368) at disease onset, after adjustment for time to biopsy.

Conclusion:

This study reveals an association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients, CMAS and MMT8. This shows how immunohistochemical staining of MxA on muscle tissues has the potential of providing more insight into pathogenesis of JDM and may help develop more targeted therapies for JDM patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-myxovirus-resistance-protein-a-a-possible-marker-of-muscular-disease-activity-in-juvenile-dermatomyositis/