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 18th week (100% of the samples negative) becoming positive from the 24th 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
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