Background/Purpose: We previously reported (Arthritis Rheum 2012;64 Suppl 10:1670) that miRNA array studies of diagnostic muscle biopsies obtained from untreated children with Juvenile Dermatomyositis (JDM) identified 19 differentially expressed miRNAs in JDM muscle compared to healthy orthopedic controls.  Downregulation of miR-10a and miR-10b headed the list with fold changes of -1.96, adjusted p=0.0028, and fold change of -1.62, adjusted p value= 0.0027, respectively. miR-10a and miR-10b are located on separate chromosomes (2 and 17) and regulate the NFκB pathway which controls the synthesis of inflammatory mediators.  We confirmed that plasma levels of IL- 6, IL-8, TNF-α, MCP-1, VCAM-1, but not IL-1β, were elevated in untreated JDM compared to controls.  The purpose of the present study was to determine association of the miR-10a and miR-10b downregulation in the muscle with customary clinical and laboratory findings in untreated children with JDM.

Methods: After obtaining informed consent, 24 children: 11 with a short duration of untreated disease (DUD) of less than 3 months and 13 with a long DUD of greater than 3 months were enrolled; 17 were girls. Of the 24, 19 were White and 5 were Hispanic.  The children were enrolled at the time of diagnosis and their clinical and diagnostic laboratory data examined in relation to the expression levels (qPCR) of miR-10a and miR-10b in the diagnostic muscle biopsy. The clinical variables considered were disease activity scores (DAS, skin, muscle, total score), nailfold capillary end row loop number (ERL) and the blood level of von Willebrand factor antigen (vWF:Ag), DUD, and the presence of the TNF-α-308 A allele.  Healthy orthopedic patients donated muscle from the trunk or proximal limbs as controls.

 Results: Of note, decreased miR-10a, but not miR-10b, was associated with: a short DUD of less than 3 months, p=0.014; the presence of the A allele at the promoter region of TNF-α-308, p=0.006; an elevated DAS Total, p=0.03; and increased vWF:Ag level,  p=0.004.  There was no association of either decreased miR-10a or miR-10b with loss of ERL.

Conclusion: Downregulation of miR-10a, but not miR-10b, was associated with increased vWF:Ag, indicating damaged endothelial cells, and a more severe disease onset with a higher DAS, contributing to earlier diagnosis and a shorter DUD.  We conclude that miR-10a downregulation is a critical factor in JDM pathophysiology and speculate that it may be a potential therapeutic target early in the disease course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/downregulation-of-mir-10a-is-associated-with-increased-von-willebrand-factor-antigen-disease-activity-score-and-earlier-diagnosis-in-children-with-untreated-juvenile-dermatomyositis/