POS1398 NRP-1 EXPRESSION IN NZB/W F1 LUPUS NEPHRITIS: A CRUCIAL INDICATOR OF RENAL RECOVERY IN THE TREATMENT OF LUPUS NEPHRITIS
Authors: S. Sandoval-Moreno, C. Solé-Marcé, J. Cortés-Hernández
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that affects various organs, with lupus nephritis (LN) manifesting in 40-50% of SLE patients. Effectively treating and managing LN is crucial to prevent end-stage renal disease, necessitating renal replacement therapies, kidney transplantation, and, in severe cases, patient mortality. Despite extensive research exploring specific treatments and response markers, none have proven effective to date. Neuropilin-1 (NRP-1), a transmembrane receptor highly expressed in human mesangial cells, shows promise in the context of LN recovery. Studies indicate that the absence of the NRP-1 gene leads to increased proteinuria and glomerulosclerosis [1]. Renal expression of NRP-1 has been identified in lupus nephritis patients [2]. Further research on LN patients has unveiled higher NRP-1 expression in responder's renal tissue, with urinary NRP-1 levels being more pronounced in treatment responders compared to non-responders [3]. NRP-1 appears to exert a positive influence on lupus nephritis renal recovery through enhanced VEGF-angiogenesis in endothelial cells, PDGFB-mediated regeneration of the mesangium, and VEGF-lymphocyte cytotoxicity [3].The overexpression of NRP-1 in responder patients and its role in renal recovery suggest its potential as a promising marker during lupus nephritis treatment. <h3>Objectives:</h3> Assess and compare urine, serum, and renal expression of NRP-1 in NZB/W F1 murine models exhibiting lupus nephritis within responder and non-responder groups at different time points to demonstrate the correlation of NRP-1 levels with renal recovery in lupus nephritis. <h3>Methods:</h3> A total of 20 NZB/W F1 mice were divided into cyclophosphamide treatment and non-treatment groups and monitored for lupus nephritis development at 22, 26, 30, 34, 38, and 42 weeks, with serum and urine collection at each time point. Renal tissue samples were obtained at the endpoint, while a subgroup of mice (N=3) was sacrificed at 26 and 34 weeks to acquire renal tissue during nephritis development. NRP-1 levels in serum and urine were determined using ELISA assays. Immunofluorescence of renal tissue was performed to obtain renal NRP-1 levels. <h3>Results:</h3> Cyclophosphamide treatment in NZB/W F1 mice led to higher NRP-1 gene expression and protein levels in urine compared to the non-treatment group (22 and 15-fold change, respectively), with no changes observed in serum samples. Immunofluorescence and gene expression analysis of renal tissue showed elevated NRP-1 levels, particularly in the glomeruli and along the tubuli (Figure 1). Survival mice at 42 weeks exhibited a tenfold change in immunofluorescence intensity for renal NRP-1 levels. Urine NRP-1 levels demonstrated a significant inverse correlation with serum and urine disease activity parameters such as anti-dsDNA, IgG, and proteinuria during the follow-up. <h3>Conclusion:</h3> Increased levels of renal-origin NRP-1 in urine or tissue during the progression of lupus nephritis in NZB/W F1 mice appear to correlate with a positive response to treatment. This observation not only validates but also reinforces earlier findings in human models, emphasizing the translational significance of NRP-1 as a reliable response marker. The study's outcomes align consistently with observations in human models, highlighting the potential practicality of NRP-1 assessments in clinical settings. This implies promising therapeutic prospects, suggesting that boosting NRP-1 levels in lupus nephritis could serve as a positive reinforcement of treatment. <h3>REFERENCES:</h3> [1] Bartlett CS.,et al. Glomerula mesangial cells recruitment and funtcion require the co-receptor neuropilin-1. Am J Physiol Renal Physiol. 2017; 313: F1232-1242. [2] Vadasz Z., et al. Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res. Ther. 2012;14:R146. doi: 10.1186/ar3881. [3] Torres-Salido MT., et al. Urinary neuropilin-1: a predictive biomarkers for renal outcome in lupus nephritis. Int J Mol Sci. 2019; 20:4601. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>