PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians

Background. Antibodies toM-type phospholipase A2 receptor (PLA(2)R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA(2)R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA(2)R is unknown. In this prospective study we evaluated anti-PLA(2)R, enhanced glomerular staining for PLA(2)R and variations in PLA(2)R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. Methods. A total of 114 adult PMN patients were studied. Anti-PLA(2)R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA(2)R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by TaqMan assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. Results. Of 114 patients, 66.7% showed elevated serum antiPLA(2)R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA(2)R. A total of 82% of patients had PLA(2)R-related disease. Reduction in serum anti-PLA(2)R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing > 90% reduction in the antiPLA(2)R titer achieved remission of the nephrotic state, whereas of those showing < 50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA(2)R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA(2)R levels. Conclusion. To conclude, anti-PLA(2)R and enhanced glomerular PLA(2)R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA(2)R titer correlated with response to therapy.