Aim

The aim of the study was to assess the combined predictive value of serum interleukin-17 (IL-17) and TNF-like weak inducer of apoptosis (TWEAK) for renal flare in patients with systemic lupus erythematosus (SLE) and quiescent disease.

Material and methods

A prospective, multicentre cohort study was conducted involving 256 patients with SLE and clinically quiescent lupus nephritis. Serum IL-17 and TWEAK levels were measured at baseline and at 3-month intervals over 24 months. The primary outcome was renal flare, defined according to the modified SLE Disease Activity Index 2000 (SLEDAI-2K) renal domain criteria. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis and Cox proportional hazards models.

Results

Over the follow-up period, 42 (16.4%) patients developed renal flare. Serum IL-17 and TWEAK levels were significantly higher in patients who experienced flare compared to those who did not (IL-17: 28.4 ±9.7 vs. 12.3 ±5.1 pg/ml, p < 0.001; TWEAK: 324.6 ±87.2 vs. 187.3 ±62.4 pg/ml, p < 0.001). The combination of IL-17 greater than 20 pg/ml and TWEAK greater than 250 pg/ml demonstrated the highest predictive value, with an area under the curve (AUC) of 0.89 (95% CI: 0.84–0.94), sensitivity of 85.7%, and specificity of 88.3%. In multivariable Cox regression analysis, the high-risk IL-17/TWEAK combination predicted renal flare with a hazard ratio of 8.9 (95% CI: 4.2–18.7, p < 0.001), independent of conventional biomarkers.

Conclusions

Combined assessment of serum IL-17 and TWEAK may enable effective risk stratification for renal flare in patients with clinically quiescent lupus nephritis, with a potential prediction horizon of up to 12 months. External validation is necessary prior to clinical application.