title: PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians.
abstract: 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.
  
  
  
  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 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Raja
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ritambhra
authors.initials: R
authors.lastname: Nada
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Kumar
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Rathi
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Harbir Singh
authors.initials: HS
authors.lastname: Kohli
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Gupta
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Sakhuja
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India George Institute for Global Health, New Delhi, India University of Oxford, Oxford, UK.
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D054507:Receptors, Phospholipase A2 / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2
keywords: autoantibodies; glomerulonephritis; membranous nephropathy; nephrotic syndrome; proteinuria