Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity.Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity.Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group).Results: The secretion of urine sema3A was found to be signi cantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006).Urine sema3A was signi cantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity.Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
BackgroundSemaphorins 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].ObjectivesTo assess urine sema3A secretion in SLE patients with and without renal involvement compared to rheumatoid arthritis patients as disease control and healthy controls.Methods50 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).ResultsThirty-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.ConclusionUrinary 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,...
Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
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