Abstract
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.
Highlights
Cutaneous lupus erythematosus (CLE) is a disfiguring disease that can exist as an independent entity or as a manifestation of systemic lupus erythematosus (SLE) where up to 70% of patients experience lesions during their disease course [1]
In order to develop a large database of expression changes in both Discoid lesions (DLE) and Subacute CLE (SCLE), we utilized Formalin-fixed paraffin embedded (FFPE) biopsies to isolate RNA and to conduct expression profiling using Affymetrix ST2.1 microarrays
In order to capture the broadest summary of differentially expressed genes (DEGs) in DLE vs. normal or SCLE vs. normal, we evaluated expression changes using a q-value
Summary
Cutaneous lupus erythematosus (CLE) is a disfiguring disease that can exist as an independent entity or as a manifestation of systemic lupus erythematosus (SLE) where up to 70% of patients experience lesions during their disease course [1]. Subacute CLE (SCLE) is an inflammatory lesion with associated erythema in papulosquamous or annular formations. SCLE does not scar but depigmentation can occur [5]. Discoid lesions (DLE) are often circular and frequently lead to alopecia and scar formation [5]. SCLE lesions have a higher propensity for photo-provocation [6] and a more robust inflammatory infiltrate following ultraviolet B (UV) exposure [7]. The pathogenic mechanisms which govern the differences between DLE and SCLE remain poorly defined, and this is reflected by the refractory nature of cutaneous lesions to usual lupus therapies and no clear treatment guidelines that differentiate the subtypes [8]
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