1. PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians.
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Ramachandran, Raja, Kumar, Vinod, Kumar, Ashwani, Yadav, Ashok Kumar, Nada, Ritambhra, Kumar, Harsha, Kumar, Vivek, Rathi, Manish, Kohli, Harbir Singh, Gupta, Krishan Lal, Sakhuja, Vinay, and Jha, Vivekanand
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KIDNEY diseases , *PHOSPHOLIPASE A2 , *ALLELES , *SOUTH Asians , *KIDNEY glomerulus , *HLA histocompatibility antigens , *DISEASES , *GENETICS - Abstract
Background. Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 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-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by Taq- Man 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 anti- PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R 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 anti- PLA2R 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 PLA2R1 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-PLA2R levels. Conclusion. To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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