AB0189 DECREASED URINE SEMAPHORIN 3A SECRETION PREDICTS THE EXTENT OF RENAL DAMAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS. (June 2019)

• Record Type: Journal Article
• Authors: Rimar, Doron; Lidar, Merav; Eiza, Nasrin; Toubi, Elias; Silawy, Amal; Slobodin, Gleb; Rosner, Itzhak; Rosenbaum, Michael; Awisat, Abid; Boulman, Nina; Kaly, Lisa; Ginsberg, Shira; Jiries, Nizar; Vadasz, Zahava
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 1551
• Page End: 1552
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.3456
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Semaphorins are a family of proteins, involved in axon-guidance, malignancy spread and angiogenesis. Semaphorin 3A (sema3A) is recognized also as "immune semaphorin", it is expressed on regulatory T cells and has been shown to enhance their inhibitory effect of CD4+ T cell pro-inflammatory function and replication. We have reported a decreased serum levels of sema3A in systemic lupus erythematosus (SLE) compared to healthy controls and in correlation with SLE disease activity [1]. Sema3A was found to be over expressed in podocytes and epithelial cells in in animal models with diabetic nephropathy. Increased urinary sema3A was also detected in diabetic patients with proteinuria and in contrast-induced acute renal injury [2-3]. Objectives: To assess urine sema3A secretion in SLE patients with and without renal involvement compared to rheumatoid arthritis patients as disease control and healthy controls. Methods: 50 ml of fresh urine samples were collected, centrifuged and the supernatant was then concentrated up to 50 times the initial concentration and subjected to specific human Sema3A ELISA kit (MBS732622, San Diego, CA, USA). Results: Thirty-eight lupus patients fulfilling the 2012 SLICC criteria were recruited, 33 (87%) of whom were women, at a mean age of 35±12 years. Eight patients had active nephritis (21%) and additional 5 had a history of nephritis but were in remission. APLA was diagnosed in 13 (34%) of patients. Disease activity was evaluated by the Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K) and was 8.2±7.7. Sema3A was lower in lupus patients compared to rheumatoid arthritis and healthy controls, 4.9±3.9 ng/mL, 8.5±2.7ng/mL, 9.855±1.7ng/mL, p=0.0006. Lupus nephritis patients demonstrated lower urine sema3A concentration compared to lupus patients without renal involvement 4±3.4 ng/ml, 6.5±3.8 ng/ml, p=0.03. Sema 3A reversely correlated with proteinuria r=-0.43 p=0.006 and SLEDIA2K -0.3, p=0.04, but not with creatinine concentration, disease duration and complement concentration. There was no difference in urinary sema3A between SLE patients with or without APLA syndrome. Conclusion: Urinary excretion of Sema 3A was found to be decreased in the SLE patients with renal disease, reversely correlating with disease activity and proteinuria. These findings are in line with previous reports of decreased serum level of Sema3A in SLE, that may result in reduced efficacy of regulatory T cells, driving autoimmunity and kidney damage. The discrepancy between low sema3A urinary excretion in SLE nephropathy and increased urinary secretion in other "non- auto immune" conditions with renal damage, suggests that sema3A in the kidneys is protective in autoimmune diseases and detrimental in "non-auto immune" conditions. This differential effect of sema3A may has to do with different populations of effector cells and different expression of sema3A receptors (nuropilin1). Further studies should evaluate semphorin 3A role in lupus nephritis and its potential as a treatment option. References: [1] Vadasz Z, Haj T, Halasz K, Rosner I, et al. Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res Ther;14(3):R146. [2] Mohamed R, Ranganathan P, Jayakumar C, et al. Urinary semaphorin 3A correlates with diabetic proteinuria and mediates diabetic nephropathy and associated inflammation in mice. J Mol Med (Berl)2014;92:1245-1256. [3] Ning L, Li Z, Wei D, et al. Urinary semaphorin 3A as an early biomarker to predict contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention. Braz J Med Biol Res. 2018;51(4) Disclosure of Interests: None declared