Phospholipase A2 Receptor Antibody IgG4 Subclass Improves Sensitivity and Specificity in the Diagnosis of Idiopathic Membranous Nephropathy

Aims: The aim of this study was to develop a new method for detecting anti-phospholipase A2 receptor-IgG4 to improve the sensitivity and specificity in the diagnosis of idiopathic membranous nephropathy (IMN). Methods: A highly sensitive quantitative assay was developed for the detection of serum anti-phospholipase A2 receptor-IgG4 with europium chelation by time-resolved fluoroimmunoassay (TRFIA), and a mouse anti-human IgG4 tracer was prepared using europium chelation for detection. The specificity and sensitivity of anti-phospholipase A2 receptor-IgG4 in the diagnosis of IMN were further assessed in patients with different kidney diseases. Results: The detection limit of anti-PLA2R-IgG4 was 0.69 ng/mL. The measurement range of anti-PLA2R-IgG4 TRFIA was 0.69-2,500 ng/mL. Mean serum anti-PLA2R-IgG4 was 21.27 +/- 15.15 ng/mL in 45 healthy volunteers, 31.08 +/- 18.17 ng/mL in 29 IgA nephropathy patients, 49.10 +/- 34.32 ng/mL in 8 lupus nephropathy patients, and 10,324.11 +/- 17,030.40 ng/mL in 30 IMN patients. The anti-PLA2R-IgG4 cutoff concentration was >161.2 ng/mL with the sensitivity of 90.0% and specificity of 100% in the diagnosis of IMN. However, the cutoff for other kidney diseases was lower than 161.2 ng/mL. Conclusion: The serum anti-phospholipase A2 receptor IgG4 detected with the method developed in this study has higher sensitivity and higher specificity than total IgG in the diagnosis of IMN. (C) 2019 The Author(s) Published by S. Karger AG, Basel