Objective:.

Improved, non-invasive biomarkers are needed to accurately detect lupus nephritis (LN) activity. The purpose of this study was to evaluate five S100 proteins (S100A4, S100A6, S100A8/9 and S100A12) in both serum and urine as potential biomarkers of global and renal-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE).

Methods:.

In this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy controls using commercial ELISAs. Patients were divided into cohorts based on biospecimen availability: (1) longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, (4) cross-sectional urine. Global and renal disease activities were defined using the SLE disease activity index 2000 (SLEDAI-2K) and SLEDAI-2K renal domain score (SLEDAI-R).

Results:.

All urine S100 proteins were elevated in active LN when compared to active extrarenal disease and healthy controls. All urinary S100 protein levels decreased with LN improvement, with S100A4 demonstrating the most significant decrease. Urine S100A4 levels were also higher with proliferative as compared to membranous LN. S100A4 staining in the kidney localized to mononuclear cells, podocytes and distal tubular epithelial cells. Irrespective of the S100 protein tested, serum levels did not change with cSLE improvement.

Conclusion:.

Higher urine S100 levels are associated with increased LN activity in cSLE whereas serum S100 levels do not correlate with disease activity. Urine S100A4 shows the most promise as an LN activity biomarker given its pronounced decrease with LN improvement, isolated elevation in urine and positive staining in resident renal cells.