Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy

Autor: Kay Poulton, Lorna McWilliam, Michael Venning, Paul Brenchley, Shelley Harris, Stephen A Roberts, Durga Kanigicherla, Milind Nikam, Edward A. McKenzie, Jennet Gummadova, Colin D. Short
Rok vydání: 2013
Předmět:
Male
Time Factors
Biopsy
Kaplan-Meier Estimate
medicine.disease_cause
Glomerulonephritis
Membranous
Gastroenterology
Autoimmunity
Risk Factors
Prevalence
HLA-DQ beta-Chains
education.field_of_study
biology
medicine.diagnostic_test
Remission Induction
Middle Aged
Prognosis
Up-Regulation
Nephrology
Disease Progression
Female
Antibody
Adult
medicine.medical_specialty
Population
Renal function
Enzyme-Linked Immunosorbent Assay
Polymorphism
Single Nucleotide
HLA-DQ alpha-Chains
Membranous nephropathy
Predictive Value of Tests
Internal medicine
medicine
Genetic predisposition
Humans
education
Survival analysis
Autoantibodies
Proportional Hazards Models
Retrospective Studies
business.industry
Receptors
Phospholipase A2
medicine.disease
Immunoglobulin G
Immunology
Linear Models
biology.protein
business
Biomarkers
Zdroj: Kidney International. 83:940-948
ISSN: 0085-2538
DOI: 10.1038/ki.2012.486
Popis: 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.
Databáze: OpenAIRE
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