AB0538 Urinary levels of vcam-1 and tweak as biomarkers of lupus nephritis

Abstract

BackgroundTNF-like WEAK inducer of apoptosis (TWEAK) is able to increase the expression of various molecules involved in the inflammatory response with relevant effects also in angiogenesis. The pathological functions of TWEAK are primarily attributed to its ability to induce the expression of several pro-inflammatory cytokines, chemokines and cell adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) (1). Some previous studies (most of them in Caucasic, Afro-American and Asiatic cohorts) have demonstrated clinical utility of VCAM-1 and TWEAK as biomarkers in patients with systemic lupus erythematosus SLE (2).ObjectivesTo evaluate the diagnostic value of urinary VCAM-1 and TWEAK in a cohort of Latin-American patients with SLE.MethodsPatients meeting the revised ACR criteria for SLE were recruited from 2 different centers at Medellín and Baranquilla, Colombia. Urinary levels of VCAM-1 (uVCAM-1) and TWEAK (uTWEAK) were measured using an ELISA kit (R&D system, USA). SLE activity was measured with SLEDAI. Inactive LN was defined by the presence of: 24 hours proteinuria ≤500 mg/dl, inactive urine sediments and stable serum creatinine. Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations.ResultsOne hundred and fifty eight SLE patients were recruited (89% female) with median age of 32.8±12.1 years and median disease duration of 7.27±6.6 years. Mestizo (77%) and African Latin-American patients (20%) were majority. Mean SLEDAI score was 8.5±8.7. One hundred and four patients (64%) had lupus nephritis (LN). 76 out of 104 patients had biopsy proven LN, in 62% of cases with proliferative forms. uVCAM-1 and uTWEAK were significantly higher in patients with LN than without LN. At the same time, uVCAM-1 and uTWEAK were significantly higher in patients with active vs inactive LN (Figure). uVCAM-1 (581±1197 vs 189±256 ng/ml, p<0.001) and uTWEAK levels (3202±3778 vs 1123±1873 pg/ml, p=0.038) were significantly higher in patients with Class V LN in comparison with other LN classes. uVCAM-1 and uTWEAK levels had a mild positive correlation with SLEDAI (r=0.22 and r=0.16, respectively). In addition, uTWEAK correlated with 24 hours proteinuria (r=0.28). No significant correlation was found between uVCAM-1 and uTWEAK.Figure 1.Urinary levels of VCAM-1 and TWEAK in patients with and without LN (A and B) and in patients with active vs inactive LN (C and D).ConclusionsuVCAM-1 and uTWEAK are useful biomarkers in Latin-American patients with SLE for the identification of patients with LN and active LN. In addition, urinary levels of VCAM-1 and TWEAK were significantly more elevated in patient with membranous LN.References González-Sánchez DA, Άlvarez CM, Vásquez G, Gόmez-Puerta JA. Role of TWEAK/Fn14 signalling pathway in lupus nephritis and other clinical settings. Nefrologia. 2016. pii: S0211–6995(16)30084–4.Skeoch S, Haque S, Pemberton P, Bruce IN. Cell adhesion molecules as potential biomarkers of nephritis, damage and accelerated atherosclerosis in patients wit...

A longitudinal multiethnic study of biomarkers in systemic lupus erythematosus: Launching the GLADEL 2.0 Study Group

“…Active LN patients had higher levels of uTWEAK than patients with other glomerulopathies and healthy controls. 29 uTWEAK had also been related to class-V LN, 30 and more recently as a marker of higher risk of developing end-stage renal disease. 31…”