Purpose Cytokine dysregulation plays an important role in the pathogenesis of lupus nephritis (LN). IL-17/IL-23 axis seems to have an important influence in the development of LN. The aim of this study is to evaluate the strongest prognostic factors in a cohort of patient with LN focusing on of the impact of IL-17/IL 23 axis as emerging pathogenetic pathway on renal outcome.^1,2

Methods 91 patients with active LN (76 females and 15 males; mean age at study entry± SD, 44.1 ± 12.1, mean follow-up in months ± SD, 78.5 ± 50.1) at disease onset or at disease flare were enrolled. Laboratory, immunological and disease activity data were collected at baseline and at 6(T6),12(T12),24(T24) months and at the last follow-up(FU). 84 renal biopsies were evaluated according to ISN/RPS classification, assessing the activity and chronicity indices and the active interstitial infiltrate using the BANFF score system. Baseline IL-17 and IL-23 serum levels were assessed by ELISA in 37 patients.

Results among the 84 renal biopsies evaluated 77% belonged to class III and IV according to ISN/RPS; 41,8% of patients had a renal active interstitial infiltrate (>5%). Regardless any significative difference in the IL -17 serum levels between patients with worse versus favourable nephritis course, patients with higher IL-17 serum levels at the baseline showed higher levels of renal interstitial infiltrate and a worse renal outcome overall. Finally, at univariate and multivariate analysis for each renal outcome considered, active interstitial infiltrate (>5%) at renal biopsy and the presence of at least one antiphospholipid antibodies positivity (APL+) were associated with worse renal outcomes. In particular active inflammatory interstitial infiltrate was associated to worse renal outcome in terms of not reaching early remission in both univariate analysis (p<0,01) and multivariate analysis (OR 0.12(0.04–0.37)), while it was associated to chronic damage (p= 0,01), no persistent remission (p= 0,02), persistent proteinuria (p <0,01), and renal flare (p<0,001) in the univariate analysis. APL+ was associated to worse renal outcome in terms of early remission in both univariate analysis (p= 0,03) and multivariate analysis (OR 0.36(0.11–1.37)) as well as to chronic renal damage in univariate analysis (p= 0,04) and multivariate analysis (OR 0.77 (0.39–15.16)), while it was associated to persistent remission (p= 0,01) and persistent proteinuria (p= 0,01) in the univariate analysis. Higher IL-23 serum level was associated with persistent proteinuria (p<0,01) and chronic renal damage (p=0.05).

Conclusion interstitial inflammatory infiltrate and APL+ represent in our study the strongest predictors of worse renal outcome. A higher IL-23 serum level was found to be a negative prognostic factor suggesting a possible role of IL-17/IL 23 axis as a biomarker of a more aggressive renal disease.

References

1. Chen DY, et al. Lupus 2012.

2. Crispin JC, et al. J immunol 2008.