Urine S100 proteins as potential biomarkers of lupus nephritis activity

Abstract

BackgroundImproved, noninvasive 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 system-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE).MethodsIn this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy control subjects using commercial enzyme-linked immunosorbent assays. Patients were divided into cohorts on the basis of biospecimen availability: (1) longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, and (4) cross-sectional urine. Global and renal disease activity were defined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K renal domain score. Nonparametric testing was used for statistical analysis, including the Wilcoxon signed-rank test, Kruskal-Wallis test, Mann-Whitney U test, and Spearman’s rank correlation coefficient.ResultsAll urine S100 proteins were elevated in patients with active LN compared with patients with active extrarenal disease and healthy control subjects. All urine S100 protein levels decreased with LN improvement, with S100A4 demonstrating the most significant decrease. Urine S100A4 levels were also higher with proliferative LN than with membranous LN. S100A4 staining in the kidney localized to mononuclear cells, podocytes, and distal tubular epithelial cells. Regardless of the S100 protein tested, serum levels did not change with cSLE improvement.ConclusionsHigher 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1444-4) contains supplementary material, which is available to authorized users.

Al2O3microring resonators for the detection of a cancer biomarker in undiluted urine

“…A limit of detection of 3 nM (~36 ng/ml) was demonstrated. This value lies within the clinically relevant range demonstrated by Turnier et al for patients with lupus nephritis and can be used as a reference value for patients with bladder cancer [8,41,42]. These results show the potential of using this novel material platform to detect biomarkers in point-of-care applications using patients' urine without any sample pre-treatment and/or complicated amplification steps.…”

“…Therefore, the overexpression of S100A4 protein may be of value as a biomarker of bladder cancer progression. Urine levels of S100A4 for bladder cancer are not reported in the literature but Turnier et al showed median urine levels of S100A4 around 0.1 nM for healthy controls and median urine levels ranging from 0.5 to 1 nM for patients with lupus nephritis using a commercially available ELISA kit [8].…”

Al2O3:Yb3+ integrated microdisk laser label-free biosensor

“…Detection of a concentration as low as 300 pM of the S100A4 protein in synthetic urine is experimentally demonstrated. This falls within the concentration range being reported as clinically relevant [24], therefore showing the potential of this active platform for label-free biosensing.…”

Al<inf>2</inf>O<inf>3</inf> Microresonator Based Passive and Active Biosensors

“…2d). A lowest concentration of 3 nM was detected, which is within the clinically relevant range [8].…”