Nonlesional Skin and Blood Interferon Scores Among Patients With a History of Cutaneous Lupus.

Abstract

Interferons (IFNs) play a crucial role in systemic lupus erythematosus (SLE) pathophysiology and are increased in cutaneous lupus erythematosus (CLE) lesions and blood. Recently, IFN-stimulated genes (ISGs) have been shown to be expressed in nonlesional skin of patients with SLE, suggesting that the nonlesional skin functions as an immune-activated site. Whether this is the case in all patients with SLE remains to be understood. To compare nonlesional skin and peripheral blood mononuclear cell (PBMC) ISG expression in patients with lupus with and without a history of cutaneous lupus erythematosus. This cross-sectional study at a single-center at a tertiary referral center included patients with a history of cutaneous lupus without SLE (CLEwoSLE), patients with SLE with CLE (SLEwCLE), patients with SLE without CLE (SLEwoCLE), and healthy controls (HCs). All SLE patients met the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) classification criteria and cutaneous lupus was diagnosed by a dermatologist. Data analysis occurred from January 2024 to May 2025. ISG expression in PBMCs and nonlesional skin was assessed via calculation of IFN score. Overall, 74 of 101 participants were female individuals (73%), and the median (IQR) age varied between 44 (41-50) and 64 (53-68) years between groups. IFN scores in PBMCs were higher in SLEwCLE compared with patients with SLEwoCLE. Similarly, SLEwCLE patients showed highest levels of IFN scores in nonlesional skin. IFN scores in PBMCs and nonlesional skin were strongly correlated (r = 0.83, P < .001). 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, suggesting that patients with lupus with and without CLE comprise 2 endotypes, with stronger IFN dysregulation occurring in patients with CLE.