Type I Interferon Gene Expression and Its Association With Ocular Involvement in Systemic Lupus Erythematosus

Severalstudies have highlighted the role of Type I interferons (IFN-I) in activating inflammatory pathways in lupus. However, no previous research focused on investigating the role of IFN-I gene expression in the ophthalmologic involvement of systemic lupus erythematosus (SLE). We aimed to assess the association between the IFN-I gene signature and ophthalmologic involvement in SLE.

Cross-sectional study includes patients ≥18 years old, fulfilling the 2019 EULAR or American College of Rheumatology criteria for SLE. Ophthalmologic evaluation, the Systemic Lupus Erythematosus Disease Activity Index-2K index, and blood sample collection were performed at the time of study assessment. Peripheral blood mononuclear cells were isolated, RNA was extracted, and complementary DNA was synthesized. Gene expression of IFI27, IFI44L, IFIT1, ISG15, RSAD2, and SIGLEC1 was assessed by real-time polymerase chain reaction, using RPLP0 and EEF1A1 as reference genes for normalization. The median normalized relative quantity of the genes for each patient was used to calculate the fold change (FC) of the "Interferon Score." Group comparisons were conducted using the Mann-Whitney U test, and correlations between variables were assessed using Spearman's rank correlation coefficient.

We included 32 patients with SLE. Ocular involvement occurred in 62.5%, either due to aqueous-deficient dry eye (46.88%) or lupus retinopathy. A higher expression of the IFN-I gene was found in patients with ocular involvement (FC = 2.52 ± 1.96; P = 0.0027) compared with those without ophthalmologic changes.

The upregulation of the IFN-I gene expression was associated with ophthalmologic involvement in SLE, potentially playing a role in its pathogenesis.