Abstract
BackgroundApproximately 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.MethodsS100A8/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.ResultsSerum 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.ConclusionsFindings from this study show promise for clinical application of S100 proteins to predict active renal disease in SLE and response to treatment with RTX.
Highlights
Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease that can affect any organ of the human body
► Serum S100A12, and serum and urine S100A8/A9 (p
The study cohort included a total of 243 adult-onset patients with SLE (235 serum and 198 urine samples; 192 matched samples) and 48 healthy donors as controls (HC) matched for age (HC; urine and serum n=48; 46 matched samples)
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease that can affect any organ of the human body. We determined serum and urine concentrations of S100 proteins S100A8/A9 and S100A12 in adult-onset SLE with or without active renal disease. We tested their applicability as potential markers for renal disease and disease activity as well as their capacity to predict responses to RTX treatment in patients with active lupus nephritis (LN). Binary logistic regression was conducted to examine whether S100 protein levels (all log transformed) can predict renal disease (outcome: active=1; inactive=0) and/or response toTRTX treatment (outcome: responder=1; non-responder=0). To test associations of S100 protein levels with response to RTX treatment, crude and adjusted (for disease duration, disease activity, renal disease and steroid dose) ORs were calculated. Area under the curve (AUC) receiver operating curve (ROC) analysis was calculated for individual proteins and models, using their predicted probabilities, with outcomes ‘active renal disease’ or ‘responder to RTX’
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