Background 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 .
Objectives 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.
Methods 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.
Results 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<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<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.
Conclusions 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.
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.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.