Background The study aim is to identify a multipanel biomarkers matrix, to improve stratification and management of lupus nephritis (LN).

Methods 45 SLE-patients (age:40.5 ± 11.0) at disease onset/flare were enrolled. 28 patients with LN underwent renal biopsy, classified according to ISN/RPS and to the BANFF-score for active interstitial infiltrate (II). 15 patients had non-renal-SLE (NR-SLE). Laboratory, immunological and disease-activity data were collected at baseline and then at 6(T6) and 12(T12) months. Serum level of BAFF, IL-2, IL-6, IL-17 and IFN-alpha were assayed by ELLA-panel at each timepoint.

Results Considering LN-patients, 66% had class III/IV, 71.8% had II>5%. Performing univariate analysis for each renal outcome, focusing on histology, a significant association between higher activity index and worse prognosis in terms of remission at T12 (p= 0,04), proteinuria and renal damage development (p= 0,04 and p= 0,03 respectively) was observed. Furthermore LN patients with II>5% were less likely to achieve early remission (p= 0,04) together with those with antiphospholipid antibody (ApL) positivity (p= 0,05).

The analysis of cytokines revealed that serum levels of IL-6 were significantly higher in SLE active patients as compared to controls (LN vs R-LN, p=0.02; NR-SLE vs R-LN, p=0.02), whereas IFN-alpha levels were significantly increased only in LN patients (LN vs R-LN, p=0.01).

Serum levels of IL-6 in LN patients positively correlated with disease activity index (R=0.819; p<0.001), negatively with C3 (R= -0.608; p=0.003) and C4 (R= -0.675; p=0.01) and they were associated with histological severity, being significantly higher in patients with II>5% (p= 0.01) and positively correlating with activity index (R=0.695; p=0.01).The cytokines’evaluation in relation to outcomes revealed that NR-SLE-patients who achieved remission had baseline higher level of IL-2 than active patients (p=0.01). LN-patients with higher levels of IL-6 during the follow-up were less likely to reach remission(p=0.02) as well as those with higher levels of IL-17(p=0.01). Higher baseline levels of IL-17 were observed in patients who developed persistent proteinuria than those who didn’t (p=0.02).

Conclusion Higher disease-activity index appears as predictor of worse renal outcome. Higher IL-6 and IL-17 levels emerge as possible biomarkers of more aggressive LN. IL-2 seems to have a protective role in NR-SLE.