Background/Purpose: Patients with SLE have increased type I IFN-regulated gene expression in peripheral blood, which has been correlated with systemic disease activity. IFN-regulated gene expression is increased in patients with cutaneous lupus erythematous (CLE) in peripheral blood and target tissue, including skin samples from chronic cutaneous lupus erythematous (CCLE) and DLE. The pattern of IFN-induced protein regulation, or IFN-signature, has been shown to correlate with lymphocytic infiltrates in skin and to correlate with disease manifestations of lupus, linking it to pathogenesis of disease. These findings have led to clinical trials of a variety of targeted therapies for treatment of CLE, including antibodies inhibiting B-cells and type I IFN signaling. The current study aimed to measure expression of type-I IFN-regulated genes on skin biopsies from subacute cutaneous lupus erythematous (SCLE), DLE, and normal control patients to calculate IFN-activity scores as a measure of cutaneous IFN exposure. Patient’s IFN-activity scores were compared with serologic tests and medication use at the time of biopsy to determine what factors influence cutaneous IFN-regulated gene expression.

Methods: Skin samples were collected from 47 patients with DLE, 43 patients with SCLE, and 13 healthy controls. Gene expression was evaluated via ST2.1 microarray. Expression level of five genes were translated into cumulative IFN score. Based on Feng et al. 2006, the IFN score was calculated using summation of standardized expression levels from each of the 5 genes for each sample. Each gene score was standardized to the correlating IFN-regulated gene in the control group ((mean IFN-inducible gene SLE- mean IFN-inducible gene control)/standard deviation IFN-inducible gene control). Clinical factors including autoimmune serology results and medication use at time of biopsy were based on chart review. Data was analyzed using two-tailed t-test with reported p-values.

Results: Both SCLE and DLE showed increased IFN gene expression compared to controls (p-value <0.01) and SCLE was increased compared to DLE (p-value <0.05). ANA, anti-Ro, and anti-dsDNA positivity did not correlate with cutaneous IFN gene expression. Decreased IFN-gene expression was correlated with use of hydroxychloroquine and/or prednisone in patients with DLE (p-value <0.01), but showed no difference in SCLE.

Conclusion: IFN-regulated gene expression is elevated in SCLE and DLE and decreases with medication use in DLE. Autoimmune serology did not correlate with IFN gene expression in the skin in the current study. SCLE patients may require alternative therapies to target IFN-driven pathology in the skin.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ifn-gene-expression-is-elevated-in-subacute-cutaneous-lupus-erythematous-and-dle-and-decreases-with-treatment-in-dle/