Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy.
Antibodies to the phospholipase A2 receptor 1 (PLA2R1) have been reported in 70% of cases of idiopathic membranous nephropathy (IMN). The genetic susceptibility of IMN has been accounted for by HLA DQA1 and PLA2R1 genes. Here we retrospectively quantified PLA2R antibodies by ELISA, and genotyped DQ alleles and PLA2R1 single-nucleotide polymorphisms for association with clinical criteria for disease activity at the time of first sample and with outcome over a median total follow-up of 90 months. In 90 prevalent patients with biopsy-proven IMN, anti-PLA2R antibodies were present in 75% of patients with IMN with active disease and were significantly higher than in patients in partial or complete remission at the time of antibody measurement. There was a differential IgG subclass response (4>2>3>1) at an early stage, i.e., within 6 months of biopsy. Levels of PLA2R antibodies were significantly linked to DQA1*05:01 and DQB1*02:01. Survival analysis of patients with IMN showed that PLA2R antibodies are significantly linked with outcome. Thus, high levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up. Future therapeutic trials in IMN should monitor anti-PLA2R, as patients with a high antibody burden may benefit from earlier therapeutic intervention.
Manchester Institute of Nephrology and Transplantation, CMFT, Manchester, UK.
Durga
D
Kanigicherla
Jennet
J
Gummadova
Edward A
EA
McKenzie
Stephen A
SA
Roberts
Shelley
S
Harris
Milind
M
Nikam
Kay
K
Poulton
Lorna
L
McWilliam
Colin D
CD
Short
Michael
M
Venning
Paul E
PE
Brenchley
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D054507:Receptors, Phospholipase A2 / Q000235:genetics / Q000276:immunology*; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
D001323:Autoantibodies; D015415:Biomarkers; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D007074:Immunoglobulin G; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2