PLA2R antibody, PLA2R rs4664308 polymorphism and PLA2R mRNA levels in Tunisian patients with primary membranous nephritis.

BACKGROUND:Primary membranous nephritis is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and susceptibility and outcome. METHODS:Sixty-eight duanyu1451 patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in duanyu1451 patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction. RESULTS:Forty-three (63.2%) duanyu1451 patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant duanyu1451 to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) duanyu1451 patients, while all SLE patients and controls were negative, p<0.0001. Moreover, anti-PLA2R Ab levels were significantly higher in duanyu1451 patients (134.85 [41.25-256.97] RU/ml) than in SLE patients (3.35 [2.3-4.35] RU/ml) and controls (2 [2-2.3]), p<0.0001. Consequently, a ROC curve showed for 100% specificity a sensitivity of 94.1% at a threshold of 2.6 RU/ml. Besides, Anti-PLA2R antibodies levels were significantly associated to non-remission; p = 0.002. The rs4664308*A wild-type allele was significantly more frequent in duanyu1451 patients (0.809) than in controls (0.633) and SLE patients (0.65); p = 0.008, OR [95% CI] = 2.44 [1.24-4.82] and p = 0.016, OR [95% CI] = 2.27 [1.15-4.5], respectively. Renal PLA2R mRNA levels were significantly higher in duanyu1451 patients (218.29 [66.05-486.07]) than in TIN patients (22.09 [13.62-43.34]), p<0.0001. Moreover, PLA2R mRNA levels were significantly higher in non-remission patients (fold-factor vs. partial remission = 2.46 and fold-factor vs. complete remission = 12.25); p = 1.56 10E-8. In addition, PLA2R mRNA and anti-PLA2R Ab levels were significantly correlated, Spearman Rho = 0.958, p<0.0001. CONCLUSION:Anti-PLA2R Ab and renal PLA2R mRNA could be useful markers for duanyu1451 outcome predicting. The PLA2R rs6446308 SNP is associated with duanyu1451 susceptibility in Tunisians.

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