Biomarkers for Lupus Nephritis

Abstract

Purpose: Kidney involvement is a major clinical problem in systemic lupus erythematosus (SLE) due to its asymptomatic presentation and lack of reliable tests for prediction and monitoring. The discovery of biomarkers for lupus nephritis (LN) may permit identification of patients at risk for LN flare, improve monitoring of LN, and prevent kidney damage. Faced with the lack of reliable markers for renal disease activity, the following study was performed with the goal of identifying candidate biomarkers for renal lupus. Methods: We studied 73 SLE patients enrolled from the Hopkins Lupus Cohort via the Autoimmune Biomarkers Collaborative Network. Global SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI) and physician's global assessment (PGA). Renal-specific disease activity was assessed with the Lupus Activity Index renal subscore. Patients were classified into 3 groups: (1) active LN (renal subscore and urine protein dipstick equal or more than 2; n=29), (2) LN in remission (history of LN with biopsy and proteinuria, current renal subscore = 0 and urine protein = 0; n=27), and (3) active non-renal SLE (no history of LN, renal subscore = 0 and urine protein = 0, current SLEDAI equal or more than 6 or PGA equal or more than 1.5; n=17). Serum samples from 30 healthy controls were also included. Serum levels of IL-18, CXCL13, TWEAK and calprotectin were measured by singleplex ELISA, while MMP-7, TNF-a, CXCL10, CCL2, CCL19, IFN-g, IL-1b and IL-10 were measured on a multiplexed ELISA platform (SearchLight, Aushon Inc.). Data were analyzed using non-parametric statistical tests (Mann-Whitney U-test or Spearman's rank correlation). Results: Serum levels of both MMP-7 and IL-18 were significantly higher in the active LN group as compared to both LN in remission (MMP-7, p=0.004; IL-18, p=0.03) and active, non-renal SLE (MMP-7, p<0.0001; IL-18, p=0.01). Neither of these proteins showed a correlation with the extra-renal activity scores, suggesting that these proteins are LN-specific markers. MMP-7, IL-18, and CXCL13 levels were significantly correlated with the renal activity subscore. Levels of CXCL13 and CCL19 were significantly elevated in active LN when compared to LN in remission, while CCL2 and TNF-alpha were increased in active LN vs. active non-renal SLE (p<0.05 for all). Conclusion: Serum levels of IL-18 and MMP-7, which has not been previously associated with LN, reflect the activity of kidney disease in SLE patients and may be reliable biomarkers for LN.