Date: Sunday, October 21, 2018
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Dermatomyositis (DM) is a rare disease with both cutaneous and muscle pathophysiology. In the skin of DM patients, very little is known about the drivers of inflammation. In addition, the pathologic diagnosis of cutaneous DM is complicated by its morphologic overlap with cutaneous lupus erythematosus (CLE). Thus, it can be difficult to differentiate DM from CLE patients based on skin biopsy alone. We thus undertook this study to evaluate the gene expression changes in DM skin to understand the dysregulated genes in this disorder and to compare DM skin expression changes to our database of expression changes in CLE to determine unique and overlapping changes between the two diseases.
Methods: Thirty-six patient samples of DM skin biopsies were obtained through the University of Michigan Pathology Archives under IRB HUM72843. Validation of dermatomyositis was made via chart review for documented muscle disease, classic rash features such as Gottron’s papules, and autoantibodies. RNA was isolated from formalin-fixed, paraffin-embedded tissue and subjected to microarray analysis via Affymetrix ST 2.1 chip. Differentially expressed genes in dermatomyositis were identified via linear model (limma). DM skin biopsies were stained for interferon (IFN) α, β, and κ via immunohistochemistry.
Results: For patients included in the DM cohort, the mean age was 55.5 (SD 16.7); 9 were male, and 27 were female. Race and ethnic distribution was as follows: 28 were Caucasian, 3 were African American, 2 were Hispanic, and 3 were unspecified. Thirteen had skin-only involvement, 22 patients had both muscle and skin involved. Principal component analysis demonstrated substantial differences between DM and healthy control skin. A total of 6,382 differentially expressed genes (DEGs; FDR<=10% and fold change (FC)≥2) were identified in DM skin. There was a strong correlation between SCLE and DM DEGs; however, DM patients had 4,550 unique DEG that showed limited dysregulation in SCLE. Of the genes in common between DM and SCLE, we identified a significant type I IFN signature, including MX1, OASL, and IFIT1. Interestingly, similar to our data from CLE skin, we identified IFNκ as the most significantly upregulated type I IFN in DM skin (FC=2, q=7.2E-06). IFNε was the only other type I IFN upregulated by our array (FC=1.4; q=3.05E-02). Upregulation of IFNκ expression was confirmed by immunohistochemistry and displayed expression in the basal keratinocyte layer and in the dermis. Minimal IFNα and IFNβ staining was seen. When genes unique to DM were subjected to GO analysis, functional enrichment in pathways involving vesicle transport (q= 2.03E-05), RNA splicing (q= 2.11E-05), and neutrophil degranulation (q= 5.18E-05) were noted.
Conclusion: DM skin displays a strong type I IFN signature and upregulation of IFNκ, similar to CLE, but there are distinct regulatory pathways that separate DM from CLE that may be useful biomarkers for early identification of DM. In addition, our data suggest that targeting type I IFN pathways in DM patients may be of benefit to skin lesions.
To cite this abstract in AMA style:Nault T, Tsoi A, Reed TJ, Gharaee-Kermani M, Lowe L, Gudjonsson J, Kahlenberg M. Dermatomyositis Skin Shares Type I Interferon Overlap with Cutaneous Lupus but Displays Many Unique Expression Changes That May Serve As Biomarkers for Skin Disease [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/dermatomyositis-skin-shares-type-i-interferon-overlap-with-cutaneous-lupus-but-displays-many-unique-expression-changes-that-may-serve-as-biomarkers-for-skin-disease/. Accessed August 5, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dermatomyositis-skin-shares-type-i-interferon-overlap-with-cutaneous-lupus-but-displays-many-unique-expression-changes-that-may-serve-as-biomarkers-for-skin-disease/