Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy

Abstract

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb- (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb-/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.

Keywords: clinical nephrology; membranous nephropathy; primary glomerulonephritis.

Figure 1.

Distribution of PLA2R SAb and GAg in 572 IMN patients and the distribution of THSD7A antigen in 53 patients with out both PLA2R SAb and GAg. SAb and GAg of PLA2R were measured in 572 IMN patients. The glomerular THSD7A antigen was detected in 53 patients who were SAb−/GAg−.

Figure 2.

Positive rates of SAb and GAg in patients with IMN and positive rate when patients with SAb or GAg were counted together. Fisher exact test was used to compare the SAb+ and GAg+ rates (P<0.001).

Figure 3.

Kaplan-Meier analysis of disease remission and progression in SAb+/GAg+ and SAb-/GAg+ patients. (A) Survival curve for reaching complete remission (P<0.001). (B) Survival curve for reaching >40% decline of eGFR (P=0.27). The numbers of at-risk patients at selected time points (6, 12, 18, 24, 30, and 36 months) are indicated below the plot. Log-rank method was used to evaluate the significance of differences.

Figure 4.

Dynamic changes of SAb levels and GAg intensities from first to second biopsies in patients failed to achieve remission, relapsed and achieved remission. (A) Changes in SAb levels and GAg intensities in patients who had not achieved remission. (B) Changes in SAb levels and GAg intensities in patients who had relapsed. (C) Changes in SAb levels and GAg intensities in patients who had achieved remission. NR, no remission.

Figure 5.

Kaplan-Meier analysis for proportion of relapse in patients with sustained GAg+ and patients without GAg at the second biopsy. Patients with sustained GAg+ showed higher risk of relapse than patients without GAg (P=0.03). Log rank method was used to evaluate the significance of difference.