Elevated IFN Signatures Seen in Nonlesional Skin of Cutaneous Lupus Erythematosus Patients

Key Takeaways

• Lupus patients with a history of CLE had elevated interferon activity in nonlesional skin and blood.

• The strong observed correlation between PBMC and skin IFN scores suggests a systemic interferon signature in CLE-associated lupus, according to the authors.

• Study findings suggest immune activation beyond visible lesions. 

Patients with systemic lupus erythematosus (SLE) and a history of cutaneous lupus erythematosus (CLE) showed elevated interferon-stimulated gene (ISG) expression in blood and nonlesional skin, according to a new study.

The single-center study included individuals with CLE without SLE (CLEwoSLE), those with both CLE and SLE (SLEwCLE), patients with SLE but no CLE history (SLEwoCLE), and controls. All SLE participants met classification criteria from the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). The main outcome of interest was the interferon (IFN) score derived from ISG expression in peripheral blood mononuclear cells (PBMCs) and nonlesional skin. 

According to the study results, among the 101 participants (73% female), IFN scores in PBMCs were elevated in patients with SLEwCLE vs. those with SLEwoCLE. Nonlesional skin IFN scores were highest in the SLEwCLE group. The data also showed strong correlation between PBMC and skin IFN scores (r = 0.83, P < .001), underscoring systemic immune activation in this subgroup.

“This cross-sectional study found that ISGs, as represented by IFN scores, in nonlesional skin and PBMCs were elevated in patients with lupus with a history of CLE compared with patients without CLE,” the authors wrote in the study. “This suggests that patients with lupus with and without CLE comprise 2 endotypes, with stronger IFN dysregulation occurring in patients with CLE.”

Source: Henning S, et al. JAMA Dermatology. 2025. doi:10.1001/jamadermatol.2025.1697