THU0216 Urinary neuropilin-1: a new biomarker approach in the prognosis of lupus nephritis
Authors: M Torres-Salido, C Solé-Marcé, M Vidal, J Cortés-Hernández, J Ordi-Ros
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lupus nephritis (LN) affects up to 50% of patients with SLE and is a major cause of morbidity, despite modern therapeutic approaches [1,2]. To date, renal biopsy is still the gold standard for diagnosing and classifying the degree of renal inflammation and scarring, but its invasiveness makes it unsuitable for serial monitoring. A novel biomarker to predict the evolution of renal inflammatory injury is still needed. Neuropilin-1 (NRP-1) has important functions in adult tissues, being involved in axonal guidance, vascular endothelial sprouting, regeneration and organ repair and immunosupression [3]. <h3>Objectives</h3> Evaluate the protein and expression levels of NRP-1 at the time of the renal flare in patients with lupus nephritis and determine whether they could predict the disease progression. <h3>Methods</h3> Urine and serum of 70 patients with LN with nephrotic proteinuria, 25 patients with chronic non-lupus related nephopathy, and 25 healthy controls were analyzed by qPCR-RT and ELISA to determinate the levels of mRNA/protein of NRP-1. Immunohistochemistry of protein levels were done in renal biopsy (N=5). Urine and serum from 39 other patients with LN with nephrotic proteinuria were collected prospectively during two years. <h3>Results</h3> Increases in mRNA expression and protein concentration of NRP-1 were identified in urine samples of LN patients in flare compared with the different control groups. However, significant NRP-1 levels were found in LN patients that gone into remission compared with patients in non-remission after one year of treatment (p&lt;0.0001). Urinary VEGFA, VEGFR1, VEGFR2 and SEMA3A mRNA and protein levels were also determinate. Results were confirmed with immunohistochemistry in renal biopsies (N=5). We observed a strong correlation with NRP-1 protein levels and VEGFA protein levels (r=0.466, p&lt;0.0001). Areas under the receiver operating characteristic curve of urinary NRP-1 and VEGFA protein levels to distinguish between remission and non-remission patients were 0.8384 and 0.7706, respectively (Figure 1). In a prospective study (N=39), urinary protein NRP-1 and VEGFA levels decreased in LN patients going to complete remission; but no those with non-response that maintain their low levels during all the follow-up. <h3>Conclusions</h3> For first time, we demonstrate that urinary levels of NRP-1 might reflect the evolution of renal inflammatory injury and could be used as novel biomarker to predict the recovery of LN. <h3>References</h3> Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003;82:299–308. Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum.2003;48:3253–65. Gagnon ML, Bielenberg DR, Grechtman Z, et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. Proc Natl Acad Sci USA2000;97:2573–2578. <h3>Disclosure of Interest</h3> None declared