ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0956

An IL-18-Containing Five-Gene Signature Distinguishes Histologically Identical Dermatomyositis and Lupus Erythematosus Skin Lesions

Alex Tsoi1, Mehrnaz Gharaee-Kermani2, Celine Berthier1, Tori Nault3, Grace Hile2, Shannon Estadt4, Matthew Patrick1, Rachael Wasikowski1, Allison Billi1, Lori Lowe1, Tamra Reed1, Johann Gudjonsson5 and J. Michelle Kahlenberg6, 1University of Michigan, Ann Arbor, 2University of Michigan, Ann Arbor, MI, 3University of Michigan, Canton, MI, 4University of Michigan, Ypsilanti, MI, 5University of Michigan, Ann ArborUniversity of Michigan, 6Division of Rheumatology, University of Michigan, Ann Arbor, MI

Meeting: ACR Convergence 2020

Keywords: , ,

Session Information

Date: Saturday, November 7, 2020

Title: Muscle Biology, Myositis & Myopathies (0955–0959)

Session Type: Abstract Session

Session Time: 10:00AM-10:50AM

Background/Purpose: Skin lesions in dermatomyositis (DM) patients are common, frequently refractory, and have prognostic significance.  Histologically, DM lesions appear similar to cutaneous lupus erythematosus (CLE) lesions and frequently cannot be differentiated.  We thus undertook to examine the transcriptional profile of DM biopsies and compared them to CLE lesions in order to identify unique features.

Methods: For the inquiry cohort, 43 skin biopsies from 36 unique DM patients were identified within the University of Michigan Pathology Database.  Comparative cases of 43 subacute cutaneous lupus erythematosus (SCLE) and 47 discoid lupus erythematosus (DLE) biopsies were similarly acquired. RNA was isolated and expression analysis was completed through the University of Michigan Advanced Genomics core using Affymetrix Human Gene ST 2.1 array plates for transcriptional analysis. Following normalization, 5-fold cross-validation was used to train random forest classifiers for genes that are only up-regulated in the control vs DM comparison microarray but not in the control vs CLE comparison (restricted to genes with p >0.5 and log2 FC< |log21.5|). A secondary validation cohort was analyzed by real-time quantitative PCR and two additional patients underwent single-cell RNA sequencing.  Protein expression was confirmed by immunohistochemistry.

Results: Type I interferon (IFN) signaling, including upregulation of IFN kappa, was a common pathway in both DM and CLE, but CLE also exhibited other inflammatory pathways.  Importantly, DM lesions could be distinguished from CLE by a five-gene biomarker panel that included upregulation of IL18. Using single-cell RNA-sequencing, we further identified keratinocytes and monocyte/macrophages as the source of increased IL-18 in DM skin. 

Conclusion: The novel molecular signature identified in this study has significant clinical implications for differentiating DM from CLE lesions, and we have highlighted the potential role for IL-18 in the pathophysiology of DM skin disease. Further work should examine the potential for anti-IL-18 directed therapies to treat DM skin lesions.

Disclosure: A. Tsoi, None; M. Gharaee-Kermani, None; C. Berthier, None; T. Nault, None; G. Hile, None; S. Estadt, None; M. Patrick, None; R. Wasikowski, None; A. Billi, None; L. Lowe, None; T. Reed, None; J. Gudjonsson, Celgene, 2; J. Kahlenberg, AstraZeneca, 5, Bristol Myers Squibb, 2, 5, Eli Lilly, 5, Avion Pharma, 5, Celgene, 2.

To cite this abstract in AMA style:

Tsoi A, Gharaee-Kermani M, Berthier C, Nault T, Hile G, Estadt S, Patrick M, Wasikowski R, Billi A, Lowe L, Reed T, Gudjonsson J, Kahlenberg J. An IL-18-Containing Five-Gene Signature Distinguishes Histologically Identical Dermatomyositis and Lupus Erythematosus Skin Lesions [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/an-il-18-containing-five-gene-signature-distinguishes-histologically-identical-dermatomyositis-and-lupus-erythematosus-skin-lesions/. Accessed .

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