AB0133 Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein-1 in a murine model of systemic lupus erythematosus. (23rd January 2014)

• Record Type: Journal Article
• Authors: Vagnani, S.; Tani, C.; Carli, L.; Querci, F.; Talarico, R.; Baldini, C.; Della Rossa, A.; Bombardieri, S.; Mosca, M.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A826
• Page End: A826
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.2456
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Monocyte Chemoattractant Protein-1 (MCP-1) are promising biomarkers in lupus nephritis (LN). Recent data in human and mice systemic lupus erythematosus (SLE) highlight their potential involvement in LN pathogenesis; however controversial data exist on their role as marker of renal disease activity or damage. Objectives: The present study is aimed at evaluating urinary levels of NGAL and MCP-1 in a murine SLE model. Methods: Eight-weeks old female New Zealand Black/ White F1 mice (NZ) were used as SLE models and were compared to eight-weeks old C57BL6/J mice. In order to follow the disease course, body weight was periodically monitored and urinary protein excretion was weekly detected by dipstick analysis (Combur Test M; Roche). Weekly the urine samples were used to evaluate NGAL and MCP-1 levels by immunoassorbent assays (Mouse MCP-1 Elisa kit, Thermo Scientific; Mouse NGAL Elisa kit, Bioporto Diagnostics). At different disease stages (8, 18, 24, 30, 36, 40 weeks) the animals weresacrificed and peripheral blood serum samples were collected. Anti-dsDNA autoantibodies were analyzed by the enzyme immunoassorbent assay (ELISA) method using a commercial kit according to the manufacturer's instructions (Mouse anti-dsDNA IgG ELISA Kit, Alpha Diagnostics International). Results: In the NZB/NZW F1 mice the average weight was 14.4 g at 8 weeks of age and it increased until week 36. The mean increase from week 8 to week 36 was 7.4 g. The mean urinary excretion of proteins was 72±34 mg/dl at 8 weeks of age and it increased in the course of the disease: 293±340 mg/dl and 624±469 mg/dl at 18 and 24 weeks of age. From week 8 to week 36 NGAL and MCP-1 urinary levels were not statistically significant while an important peak was detected on day 40: 2.00±0.94 ng/mland 5954±3921pg/ml respectively. In the NZB/NZW F1 mice serum titers of IgG auto-antibodies with specificity for dsDNA were negative until the 18 th week (100% of the samples negative) becoming positive from the 24 th week of age (70% of the samples positive). During the disease course no clinical and serological changes were observed in C57BL/6J mice; in particular, anti-dsDNA autoantibodies titers were negative in all experimental groups and urinary MCP-1 and NGAL concentrations did not increase in the observing time. Conclusions: The NZB/NZW F1 mice show abnormal clinical and serological parameters that tend to accrue over time during the disease course. While the appearance of anti-dsDNA autoantibodies is associated with increase in proteinuria, in our model urinary NGAL and MCP-1 seem to come after the first signs of the renal disease and they could represent late renal disease markers. Disclosure of Interest: None Declared