Anti-Phospholipase A2 Receptor Antibody as Prognostic Indicator in Idiopathic Membranous Nephropathy

Abstract

Background: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. Methods: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. Results: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). Conclusion: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy

“…Several studies showed different positivity rates in patients with nephrotic-range proteinuria compared with those of the entire cohort; therefore, the prevalence of antibodies was influenced by the proportion of patients with active disease [ 10 , 11 , 14 ]. In two previous studies on Korean patients with primary MN, the prevalence of anti-PLA2R antibodies was reported to be 69% as measured by western blotting and 44.1% as measured by ELISA [ 10 , 16 ]. In these two studies, some patients who were tested for PLA2R-Ab using both ELISA and western blotting showed that the ELISA test was less sensitive than western blotting [ 16 ].…”

“…In two previous studies on Korean patients with primary MN, the prevalence of anti-PLA2R antibodies was reported to be 69% as measured by western blotting and 44.1% as measured by ELISA [ 10 , 16 ]. In these two studies, some patients who were tested for PLA2R-Ab using both ELISA and western blotting showed that the ELISA test was less sensitive than western blotting [ 16 ]. Even though serum samples for measurement were collected at the time of renal biopsy in the absence of the effect of immunosuppressive treatment in all these studies and the current study, differences in disease activity in the patients from each study and the different assays used for measurement might influence the observed prevalence.…”

“…Therefore, selection of patients with high risk for progression to ESRD, who are required to receive immunosuppressive therapy, is crucial when treating primary MN. So far, implementation of immunosuppressive therapy has been based on follow-up measurements of proteinuria and renal function, but recent studies have suggested measuring anti-PLA2R antibodies to guide decision making in primary MN [ 16 – 18 ]. Similarly, in this study, we found a significant difference in the clinical outcome according to anti-PLA2R reactivity.…”

A Proposal for a Serology-Based Approach to Membranous Nephropathy

“…A clinically highly relevant question is whether a positive PLA2R serology reliably excludes secondary MN and obviates further diagnostic workup. No patients with positive PLA2R Ab 1, [23][24][25][26] or glomerular PLA2R 13 were reported in a number of studies of well defined groups of secondary MN. In particular, class 5 SLE seems to be almost uniformly PLA2R negative, consistent with the pathophysiology of immune complex deposition in SLE.…”

Potential urine proteomics biomarkers for primary nephrotic syndrome

“…While almost all patients with MCD sustain their renal function for their lifetime, two-thirds of patients with MN progress to end-stage renal disease within 5–15 years, and about half of patients with FSGS who do not respond to steroid treatment will eventually require renal replacement therapy [1, 12]. Idiopathic MN is the most common glomerulonephropathy in adults manifesting NS [2]; however, it is difficult to non-invasively diagnose MN and predict prognosis [13, 14]. Circulating phospholipase A2 receptor antibodies are associated with MN but not found in all patients with MN.…”