Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.

BACKGROUND: The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). METHOD: Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested. RESULTS: Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup. CONCLUSIONS: Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.

Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre-eclampsia.

OBJECTIVES: Pre-eclampsia is associated with changes in the hemostatic system and endothelial status. Urinary 11-dehydrothromboxane B2/creatinine (11-DTXB2/Cr) is a marker for platelet activation and vascular constriction, thrombin-antithrombin complex (TAT) for thrombin formation, serum thrombomodulin (TM) for endothelial damage, and beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) for platelet activation and releasing reaction. The present study attempted to evaluate these five markers in normotensive pregnancy and pre-eclampsia. METHODS: These five markers were simultaneously measured in urine and blood samples from 25 women who were not pregnant (group 1, controls), 31 women with normotensive pregnancy (group 2, second controls), 22 women with mild pre-eclampsia (group 3), and 21 women with severe pre-eclampsia (group 4). The average gestational age was 36 wk. RESULTS: The 11-DTXB2/Cr, TAT, and beta-TG levels were significantly higher (P < 0.01) in groups 2, 3, and 4 than in group 1. The TM and beta-TG levels were significantly higher (P < 0.05) in group 3 than in group 2. The TM, beta-TG, and PF-4 levels were increased significantly (P < 0.05-0.01) in group 4 compared to those in groups 1, 2, and 3. CONCLUSION: Platelet aggregation, vascular constriction, and thrombin formation (detected by 11-DTXB2/Cr and TAT) may be markedly enhanced even in group 2, but further enhancement may be relatively slight in groups 3 and 4. In contrast, endothelial damage (determined by TM) and platelet release of PF-4 may not increase significantly in group 2, but they may increase in group 4. Platelet-release of beta-TG may be enhanced in groups 2, 3, and 4. Endothelial damage and platelet-releasing reaction (detected by PF-4 and beta-TG) may be significantly more enhanced in group 4 than in group 3.

Urinary platelet factor four (Pf4) levels in mesangial IgA glomerulonephritis and thin basement membrane disease.

The aim of this study was to assess the significance of platelet factor four (Pf4) excretion in the urine of patients with mesangial IgA glomerulonephritis (IgAGN) and thin basement membrane disease (TBMD), and ascertain if Pf4 is a useful parameter to distinguish these diseases. The concentration of Pf4 in urine (Pf4) was determined by an enzyme linked immunoabsorbent assay (ELISA) in patients with IgAGN (n = 80), TBMD (n = 37), membranous nephropathy (MN) (n = 12), minimal change nephrotic syndrome (MCNS) (n = 3), crescentic glomerulonephritis (CGN) (n = 6) and in healthy controls (n = 20), and then compared with urinalysis and renal function. An immunoperoxidase method was used to examine urine sediments for the presence of platelets. Urinary Pf4 was detected in 35 out of 80 patients with IgAGN (median 0.15, range 0.07-2.5 ng/ml, n = 35), in only 2 out of 37 patients with TBMD (p less than 0.005), in all patients with CGN and in no patients from MN, MCNS or control groups. A positive correlation between urinary Pf4 levels and red blood cell counts was observed in patients with IgAGN (r = 0.876, p less than 0.001), but not in TBMD. Pf4 did not correlate with proteinuria or plasma creatinine in either group. Platelets were detected in urine in 10 out of 15 patients with IgAGN but in only 1 out of 9 patients with TBMD. Urinary red blood cell counts in all of these 24 patients were over 100,000/ml.(ABSTRACT TRUNCATED AT 250 WORDS)