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The quest for reliable biomarkers of systemic lupus erythematosus (SLE) nephritis is an area of intense contemporary research. In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology was used for urinary proteomic profiling of patients with SLE nephritis. Clinical, laboratory, and kidney biopsy data from pediatric patients with SLE ( n = 32) were analyzed. Children with juvenile idiopathic arthritis ( n = 11) served as controls. SELDI-TOF-MS was performed using ProteinChips with different chromatographic surfaces. The resulting spectra were analyzed with Bio-Rad Biomarker Wizard software. A consistent urinary proteomic signature for SLE nephritis was found, comprising eight biomarker proteins with peaks at m/z of 2.7, 22, 23, 44, 56, 79, 100, and 133 kDa. The peak intensities of these biomarkers were significantly greater in patients with SLE nephritis compared with controls and SLE patients without nephritis. These biomarkers were strongly correlated with renal disease activity and moderately with renal damage. For the diagnosis of active nephritis, the area under the receiver operating characteristic curve was ≥0.90 for 22, 23, 44, 79, and 100 kDa biomarkers. Thus, SELDI-TOF-MS has identified a urine proteomic signature strongly associated with SLE renal involvement and active SLE nephritis. [ABSTRACT FROM AUTHOR]