Abstract
At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient’s long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.
Highlights
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a broad spectrum of manifestations and organ involvement [1,2]
Attainment of complete remission in lupus nephritis is associated with significantly improved prognosis and flare rate reduction [23]
Several clinical and histological factors have been associated with bad prognosis and progression to ESRD [24,25]
Summary
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a broad spectrum of manifestations and organ involvement [1,2]. In recent years there has been increasing interest in developing novel biomarkers; few of them have been rigorously validated in large scale longitudinal studies, none have been standardized for daily clinical practice, and mainly they had been assessed for their potential as “diagnostic biomarkers”. Neuropilin-1 (NRP-1) was originally identified as co-receptor for class 3 semaphorins, a family of molecules involved in axon repulsion [5]. Besides its critical role during embryogenesis, NRP-1 has important functions in adult tissues, being involved in axonal guidance, vascular endothelial sprouting, regeneration organ repair and immunosuppression. Evidence suggests that its role as immune-regulator would be in mediating interactions between activated dendritic cells and resting T cells [6,7,8,9,10,11,12,13], and promoting regulatory T cell activity [11]
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