Ab0652 histological renal features and cytokines assessment as possible biomarkers in patients with systemic lupus erythematosus and lupus nephritis
Annals of the Rheumatic Diseases(2023)
摘要
Background Lupus Nephritis (LN) management remains a challenge for the inadequacy of the traditional parameters in identifying more severe disease and preventing renal damage. Objectives To identify a multipanel biomarkers matrix, from histological to molecular level, aiming to improve prognostic stratification and therapeutic protocol of LN patients. Methods 45 SLE patients with active disease (age: 40.5 ± 11.0 years) at disease onset or at disease flare were enrolled. 6 patients with LN in persistent remission (R-LN) (age: 43.5 ± 11.9 years) were included as controls. 28 patients had an active LN and underwent ultrasound-guided renal biopsy while 15 patients with non-renal SLE (NR-SLE) displayed cutaneous or articular manifestations. Laboratory, immunological and disease activity data were collected at baseline and then at 6(T6) and 12(T12) months. Renal biopsies were evaluated according to ISN/RPS classification, assessing the activity and chronicity indexes and the active interstitial infiltrate (II) using the BANFF score system. Serum level of BAFF, IL-2, L-6, IL-17 and IFN-α were assayed in the study cohort by ELLA panel at each timepoint. Results Considering LN cohort, 66% of the renal biopsies belonged to class III and IV; 71.8% of LN patients had a II>5%. Performing univariate analysis for each renal outcome, focusing on histological assessment, a significant association between higher activity index and worse renal prognosis in terms of remission achievement at 12 months ( p= 0,04 ), proteinuria and chronic renal damage development ( p= 0,04 and p= 0,03 respectively) was observed. Through the ROC curve analysis, a cut-off value of activity index of 7.5 was identified (sensitivity 72.7%, specificity 66.7%) [AUC: 0.77; 95% CI, 0.56-0.98; p= 0.04] for remission achievement within 12 months and proteinuria development. Furthermore, LN patients with presence of II>5% were not only less likely to achieve early remission ( p= 0,04 ) as well as those with at least one antiphospholipid antibody (ApL) positivity ( p= 0,05 ), but displayed a worse renal outcome overall, though without reaching statistical significance. The analysis of circulating cytokines revealed that serum levels of IL-6 were significantly higher in patients with active disease as compared to R-LN patients, independently from renal involvement (LN: 7.6 ± 10.0 vs R- LN: 2.1 ± 2.1, p=0.02 ; NR-SLE: 11.4 ± 17.8 vs R-LN: 2.1 ± 2.1, p=0.02 ). Moreover, baseline serum level of IFNα was significantly increased in LN patients compared to R-LN (12.1 ± 36.8 vs 1.5 ± 3.6, p=0.01 ). Serum levels of IL-6 in LN patients positively correlated with disease activity index (R=0.819; p<0.001), and negatively with C3 (R= -0.608; p=0.003) and C4 (R= -0.675; p=0.01). Furthermore, serum levels of IL-6 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 evaluation of cytokines serum levels in relation to outcome achievement revealed that NR-SLE patients with favorable course had baseline higher serum level of IL-2 than those with active disease (0.6 ± 0.2 vs 0.1 ± 0.1, p=0.01). Finally, LN patients with higher serum levels of IL-6 during the follow-up were less likely to reach remission (3.7 ± 1.8 vs 2.1 ± 1.4, p=0.02) as well as LN patients with higher serum level of IL-17 (3.4 ± 8.0 vs 0.9 ± 0.3, p=0.01 ). In particular, higher baseline serum levels of IL-17 were observed in patients who developed persistent proteinuria than those who did not (2.3 ± 2.3 vs 0.7 ± 0.5, p=0.02) and tended to remain higher also during FU, together with IL-6 serum level. Conclusion II>5%, higher disease activity index and Apl+ represent in our study the strongest predictors of worse renal outcome, among traditional parameters. Higher IL-6 and IL-17 serum levels, at baseline and during FU, emerge as negative prognostic factor suggesting a possible role as biomarkers of more aggressive LN. IL-2 seems to have a protective role in extra renal disease. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.
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关键词
ab0652 histological renal features,systemic lupus,systemic lupus erythematosus,cytokines assessment,possible biomarkers
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