1. Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis.
- Author
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Suzuki M, Wiers K, Brooks EB, Greis KD, Haines K, Klein-Gitelman MS, Olson J, Onel K, O'Neil KM, Silverman ED, Tucker L, Ying J, Devarajan P, and Brunner HI
- Subjects
- Adolescent, Albuminuria diagnosis, Arthritis, Juvenile diagnosis, Arthritis, Juvenile urine, Biomarkers blood, Biomarkers urine, Case-Control Studies, Ceruloplasmin urine, Enzyme-Linked Immunosorbent Assay, Female, Humans, Intramolecular Oxidoreductases blood, Intramolecular Oxidoreductases urine, Lipocalins blood, Lipocalins urine, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic urine, Lupus Nephritis etiology, Lupus Nephritis urine, Male, Nephelometry and Turbidimetry, Orosomucoid urine, Predictive Value of Tests, Prognosis, Proteinuria etiology, Proteinuria urine, ROC Curve, Reproducibility of Results, Serum Albumin metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Time Factors, Transferrin urine, Blood Proteins urine, Lupus Erythematosus, Systemic diagnosis, Lupus Nephritis diagnosis, Proteinuria diagnosis
- Abstract
Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), alpha1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.
- Published
- 2009
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