Urine and serum S100A8/A9 and S100A12 associate with active lupus nephritis and may predict response to rituximab treatment.

BACKGROUND: Approximately 30% of patients with the systemic autoimmune/inflammatory disorder systemic lupus erythematosus (SLE) develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably predict renal disease. The Maximizing SLE Therapeutic Potential by Application of Novel and Systemic Approaches and the Engineering Consortium aims to identify indicators of treatment responses in SLE. This study tested the applicability of calcium-binding S100 proteins in serum and urine as biomarkers for disease activity and response to treatment with rituximab (RTX) in LN. METHODS: S100A8/A9 and S100A12 proteins were quantified in the serum and urine of 243 patients with SLE from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR) study and 48 controls matched for age using Meso Scale Discovery's technology to determine whether they perform as biomarkers for active LN and/or may be used to predict response to treatment with RTX. Renal disease activity and response to treatment was based on BILAG-BR scores and changes in response to treatment. RESULTS: Serum S100A12 (p<0.001), and serum and urine S100A8/A9 (p<0.001) levels are elevated in patients with SLE. While serum and urine S100 levels do not correlate with global disease activity (SLE Disease Activity Index), levels in urine and urine/serum ratios are elevated in patients with active LN. S100 proteins perform better as biomarkers for active LN involvement in patients with SLE who tested positive for anti-double-stranded DNA antibodies. Binary logistic regression and area under the curve analyses suggest the combination of serum S100A8/A9 and S100A12 can predict response to RTX treatment in LN after 6 months. CONCLUSIONS: Findings from this study show promise for clinical application of S100 proteins to predict active renal disease in SLE and response to treatment with RTX.

Differential analysis of serum and urine S100 proteins in juvenile-onset systemic lupus erythematosus (jSLE).

Up to 80% of juvenile-onset systemic lupus erythematosus (jSLE) patients develop lupus nephritis (LN) that affects treatment and prognosis. Easily accessible biomarkers do not exist to reliably diagnose LN, leaving kidney biopsies as the gold-standard. Calcium-binding S100 proteins are expressed by innate immune cells and epithelia and may act as biomarkers in systemic inflammatory conditions. We quantified S100 proteins in the serum and urine of jSLE patients, matched healthy and inflammatory (IgA vasculitis) controls. Serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients when compared to controls. Furthermore, serum S100A8/A9, and serum and urine S100A12 are increased in jSLE patients with active as compared to patients with inactive/no LN. No differences in S100A4 levels were seen between groups. This study demonstrates potential promise for S100A8/A9 and S100A12 as biomarkers for jSLE and active LN. Findings require to be confirmed and tested prospectively in independent and larger multi-ethnic cohorts.