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Open AccessArticle

Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes

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Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
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Department of Dermatology, Department of Computational Medicine & Bioinformatics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
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Division of Rheumatology, Department of Internal medicine, University of Michigan, Ann Arbor, MI 48109, USA
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IHA Rheumatology Consultants, Ann Arbor, MI 48109, USA
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Lifebridge Health, Baltimore, MD 21215, USA
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Division of Rheumatology, Department of Internal Medicine, Cleveland Clinic Abu Dhabi, 112412 Abu Dhabi, United Arab Emirates
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Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA
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Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(8), 1244; https://doi.org/10.3390/jcm8081244
Received: 29 July 2019 / Revised: 14 August 2019 / Accepted: 16 August 2019 / Published: 17 August 2019
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making. View Full-Text
Keywords: systemic lupus erythematosus; interferon; cutaneous lupus; discoid systemic lupus erythematosus; interferon; cutaneous lupus; discoid
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Berthier, C.C.; Tsoi, L.C.; Reed, T.J.; Stannard, J.N.; Myers, E.M.; Namas, R.; Xing, X.; Lazar, S.; Lowe, L.; Kretzler, M.; Gudjonsson, J.E.; Kahlenberg, J.M. Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes. J. Clin. Med. 2019, 8, 1244.

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