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

Abstract

Background Primary membranous nephritis (PMN) 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 PMN susceptibility and outcome. Methods Sixty-eight PMN 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 PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by realtime PCR after RNA extraction. Results Forty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, p<0.0001. Moreover, anti-PLA2R Ab levels were significantly higher in PMN 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.

Mechanisms of Primary Membranous Nephropathy

“…In an Indian cohort of 114 PMN patients, rs2187668 of HLA-DQA1 was a risk factor of serum aPLA2R-Ab [ 65 ]. The risk allele of PLA2R rs4664308 in PMN development was also reported by others [ 66 ]. Both PLA2R rs4664308 and HLA-DQA1 rs2187668 SNPs are intronic [ 64 ]; their impact might be on gene expression.…”

Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression

“…Overall, 27 studies with a total of 5353 PMN cases and 10,777 controls were included in the present study. 13 – 35 The characteristics of included studies are summarized in Table 1 . Genotyping data of cases and controls are depicted in Supplemental Tables S1–S10 .…”

“…Biological features of included studies patients are illustrated in Supplemental Table S11 . Eighteen studies were included for the rs4664308 SNP, 13 – 17 , 20 , 22 , 23 , 25 , 27 , 28 , 30 , 32 – 34 13 for the rs3749117 SNP, 16 , 18 , 22 , 23 , 25 – 27 , 30 , 33 10 for the rs3749119 SNP, 13 , 18 , 20 , 25 , 29 – 33 16 for the rs35771982 SNP, 16 , 18 – 23 , 25 , 26 , 29 – 31 , 33 , 35 12 for the rs3828323 SNP, 13 , 18 , 19 , 25 – …”

Idiopathic membranous nephropathy in children: A case report

“…In children with MN, PLA 2 R-associated MN appears to be common. PLA 2 R antibody levels are closely associated with disease activity, whereas PLA 2 R antibody-negative patients often have a good prognosis[ 4 ]. MCD in children is common in male preschool children.…”

“…To date, phospholipase A 2 receptors (PLA 2 Rs) on podocytes have been considered to be the primary antigen, and the rate of PLA 2 R positivity in the renal tissue of children with IMN is nearly 32%[ 3 ]. Circulating autoantibodies to PLA 2 R have been confirmed in approximately 80% of adults with IMN and are seldom detected in secondary MN[ 4 ]. Some studies have indicated that the titer of anti-PLA 2 R antibodies reflects disease activity and urinary protein levels.…”