Anti-α-Enolase Antibodies and IL-18 as Biomarkers for Renal Disease Activity in Lupus Nephritis: A Case-Control Study

Introduction: There is a pressing need for non-invasive biomarkers to monitor lupus nephritis (LN) disease activity, as it is a critical complication. This study aimed to evaluate the role of both interleukin-18 (IL-18) and anti-α-enolase as biomarkers for predicting lupus renal disease activity. Methods: This case-control study enrolled 90 participants: 30 with active LN, 30 with inactive LN, and 30 healthy matching age and sex controls. Serum concentrations of IL-18 and anti-α-enolase were estimated. The activity of disease and organ damage were determined utilising the systemic lupus erythematosus (SLE) Disease Activity Index (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI), and the activity of renal disease was evaluated utilising the renal SLEDAI score. Results: Serum levels of both IL-18 and anti-α-enolase were significantly higher among patients with active LN (89.97 ± 14.71 ng/mL and 51.67 ± 8.84 ng/mL) compared to patients with inactive LN (24.03 ± 18.21 ng/mL and 18.53 ± 11.36 ng/mL) and controls (1.217 ± 0.611 ng/mL and 1.153 ± 0.532 ng/mL) ( P < .001). Both biomarkers positively correlated with SLEDAI-2K score (r = 0.89, r = 0.845), ESR (r = 0.689, r = 0.69), 24-hour urinary proteins (r = 0.601, r = 0.559) ( P < .001). While they both negatively correlated with e-GFR (r = −0.58, r = −0.593), complement C3 and C4 levels (r = −0.727, r = −0.665), (r = −0.567, r = −0.56), ( P < .001). ROC curve analysis had high diagnostic accuracy (AUC = 0.95), with IL-18 >25 ng/mL and anti-α-enolase >24 ng/mL yielding 96.7% sensitivity and >90% specificity for active LN detection ( P < .01). Conclusions: Anti-α-enolase antibodies and IL-18 can be useful biomarkers for detecting and monitoring renal disease activity in SLE and may serve as therapeutic targets in the future.