ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2213

Gene Expression Profiling of T Helper Subsets in Blood and Affected Muscle Tissues Reveals Differential Activation Pathways in Patients with Juvenile and Adult Dermatomyositis

Consuelo Lopez de Padilla1, Molly S. Hein1, Cynthia S. Crowson2, Richard S. Pendegraft3, Erik J. Peterson4, Emily Baechler5 and Ann M. Reed1, 1Rheumatology, Mayo Clinic, Rochester, MN, 2Health Sciences Research, Mayo Clinic, Rochester, MN, 3Biomedical Statistics and informatics, Rochester, MN, 4University of Minnesota, Minneapolis, MN, 5Medicine, University of Minnesota, Minneapolis, MN

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Muscle Biology, Myositis and Myopathies: Immunological Aspects of Inflammatory Myopathy

Session Type: Abstract Submissions (ACR)

Background/Purpose: The molecular and cellular basis for juvenile and adult dermatomyositis (JDM and ADM) presumably is similar. However, important differences in the clinical features, outcome and associated disorders suggest that different mechanisms, at least partially, may be involved. The aim of this study was to identify shared and differential molecular pathways in peripheral blood and affected muscle between JDM and ADM, and examine their association with disease activity.

Methods: Cytokine mRNA expression profiles were analyzed in paired PBMCs and muscle specimens in 7 JDM and 5 ADM. In addition, cytokine mRNA expression in blood in 21 ADM and 26 JDM subjects over 2 study visits (baseline and 6 months visit). Disease activity was also measured by IMACS core set measures and other validated tools. Expressions of type 1 helper (Th1)-related genes (IL-2, IL-12β, IFN-γ, TBX21, STAT4, TNFα, TNFSF1), Th2 (IL-4, IL-5, IL-9, IL-10, IL-13, IL-12p70, STAT6, GATA3, IRF4), Th17 (IL-1β, IL-6, IL-21, IL-23A, IL-17A , IL-17D,  IL-17F, IL-27, TGF-β1, STAT3, RORC), Tregs (FoxP3+, STAT5β), Th22 (AHR, IL-22) and Tfh (BCL6), and of innate-related genes (MIP-1α/CCL3, CCL8/MCP2, IFNα2, IFN-β and IL-8) were examined using a custom RT2 Profiler PCR Array. Wilcoxon tests, Spearman correlations and paired t-tests were used for analysis. All reported p-values were adjusted for multiple comparisons using the Bonferroni method.

Results: Expressions of cytokine mRNAs for IL-23A (p<0.001), IL-6 (p<0.001), IL-17F (p=0.022), IRF4 (p<0.001), and BCL6 (p=0.014) were significantly up-regulated in blood of JDM compared to ADM. In the muscle, however, there were no significant differences between JDM and ADM, probably due to the small sample sizes. We also compared the gene expression profiles in paired blood samples and muscle biopsies among 12 patients (7 JDM and 5 ADM). Expressions of AHR (p=0.007), IFN-γ (p=0.054), IL-23A (p=0.050), STAT5β (p=0.022), TBX21 (p=0.047), TGF-β1 (p=0.036), TNFSF1 (p=0.011), CCL3 (p=0.022) were found at higher levels in muscle compared to blood of JDM/ADM patients, the majority of these genes were Th1 and Th17 pathway-associated genes. Finally, among 16 patients with samples tested at baseline and 6 months visits, there were no significant correlations between changes in gene expression profiles in blood and disease activity measures over time.

Conclusion: We observed differences in gene expression profiling in blood between new onset JDM and ADM, many of the overexpressed genes in JDM were Th17-cytokine genes. The upregulation of Th1 and Th17-related genes was apparent in muscle compared to blood in JDM/ADM patients and may reflect activation of different Th pathways between muscle and blood.

Disclosure:

C. Lopez de Padilla,
None;

M. S. Hein,
None;

C. S. Crowson,
None;

R. S. Pendegraft,
None;

E. J. Peterson,
None;

E. Baechler,
None;

A. M. Reed,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gene-expression-profiling-of-t-helper-subsets-in-blood-and-affected-muscle-tissues-reveals-differential-activation-pathways-in-patients-with-juvenile-and-adult-dermatomyositis/