Serum Interferon-γ as a Biomarker of Cardiovascular Complications in Systemic Lupus Erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is associated with an elevated risk of premature cardiovascular disease (CVD). Traditional serological markers and standard lipid indices often demonstrate limited utility in stratifying this macrovascular risk.  Purpose: This study evaluates the potential of the Th1-cytokine Interferon-γ (IFN-γ) to discriminate concurrent CVD complications in patients with SLE and explores its cardiometabolic associations. Methods: A case-control study was conducted with 120 age- and gender-matched participants, divided equally into three groups (n = 40 per group): SLE with CVD, SLE without CVD, and healthy controls. Serum concentrations of IFN-γ, C-reactive protein (CRP), anti-dsDNA autoantibodies, and lipid profiles were quantified. Statistical and Receiver Operating Characteristic (ROC) curve analyses were utilized to evaluate diagnostic potential and inter-variable associations. Results: Both CRP and anti-dsDNA levels were significantly elevated in the two SLE cohorts compared to controls (p = 0.001); however, they did not significantly differentiate between SLE patients with and without concurrent CVD. Standard lipid fractions showed no significant variation across the three groups. In contrast, systemic IFN-γ levels were significantly higher in the CVD-complicated SLE cohort (218.17 ± 21.9 pg/mL) compared to the uncomplicated SLE group (196.06 ± 19.5 pg/mL) (p = 0.001). ROC analysis indicated a strong discriminative capacity for IFN-γ in identifying SLE-CVD (AUC = 0.973; sensitivity 95.0%, specificity 97.5% at a cutoff > 162.29 pg/mL). Bivariate analysis demonstrated a positive correlation between IFN-γ and total cholesterol specifically within the CVD-complicated subgroup (r = 0.336, p = 0.034). Conclusion: IFN-γ shows strong potential as a discriminative biomarker for concurrent cardiovascular complications in SLE, demonstrating better stratification than conventional inflammatory and lipid markers within this study cohort. Its correlation with total cholesterol in the CVD phenotype suggests a possible Th1-mediated cardiometabolic link that warrants further longitudinal investigation.