Urinary proteomics revealed prostaglandin H2D-isomerase, not Zn-α2-glycoprotein, as a biomarker for active lupus nephritis

Although renal histopathology is the gold standard for the diagnosis and prognosis of lupus nephritis (LN), the invasiveness of renal biopsy warrants the discovery of novel non-invasive diagnostic and prognostic biomarkers. In the present study, urine samples from 10 LN patients (5 active and 5 inactive) were analyzed by two-dimensional gel electrophoresis (2-DE) to screen for potential biomarkers of active LN. Quantitative analysis and statistics revealed 16 protein spots whose levels significantly differed between groups. These proteins were successfully identified by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF MS/MS). Among these potential candidates, differential levels of urinary Zn-α2-glycoprotein (ZA2G) and prostaglandin H2D-isomerase (PGDS) were further validated by enzyme-linked immunosorbent assay (ELISA) in another independent group of 78 subjects, including 30 active LN, 26 inactive LN, 14 non-LN glomerular diseases, and 8 healthy normal individuals. Whereas ZA2G levels were elevated in urine of patients with active LN and non-LN glomerular diseases, PGDS was elevated only in the urine of the active LN group. Urinary PGDS, not ZA2G, may serve as a biomarker for active LN and upon validation in larger studies, may become the non-invasive test to evaluate the disease activity in future management of LN.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (339 K)Download as PowerPoint slideHighlights► Two novel urinary biomarkers for active LN were discovered and validated. ► ZA2G levels were elevated in urine with active LN and non-LN glomerular diseases. ► PGDS was elevated only in the urine of the active LN group. ► Upon validation in larger studies, PGDS may be non-invasive test for LN activity.