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Abstract
This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the −670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the −670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) and in situ hybridization (FISH) and apoptotic features by TUNEL. Results. The −670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the −670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria.
Highlights
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and multiorgan involvement, including kidney damage in 60% of patients [1, 2]
The A and G allelic frequencies were 0.41 and 0.45, respectively. These results indicated that the Fas G allele was associated with susceptibility to SLE, with odds ratios (ORs) of 1.86 (P = 0.03) and 2.23 (P = 0.05) for the dominant and recessive models, respectively (Table 1)
We sought to determine whether the association between lupus nephritis (LN) and soluble Fas (sFas) levels is associated with the −670 Fas polymorphism
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and multiorgan involvement, including kidney damage in 60% of patients [1, 2]. Renal involvement is a serious complication of SLE because it can lead to high rates of morbidity and mortality [6]. The diagnosis of glomerulonephritis is suspected when proteinuria and urinary sediment alteration are accompanied by arterial hypertension. These data may predict kidney involvement, renal biopsy remains the gold standard for the diagnosis and classification of LN. And traditionally used urinary biomarkers include proteinuria >0.5 g/L, alterations in renal ultrasound results, and changes in the rate of glomerular filtration, indicating the degree of renal function.
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