Serum Anti-PLA₂R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

Abstract

Background: M-type phospholipase A₂ receptor (PLA₂R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA₂R (gPLA₂R) and the associations of serum anti-PLA₂R antibody (sPLA₂R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA₂R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA₂R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA₂R and sPLA₂R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA₂R or sPLA₂R-Ab positive. The sPLA₂R-Ab titre, not gPLA₂R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA₂R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA₂R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA₂R intensity and outcome. Conclusions: These data indicate that sPLA₂R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA₂R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.

Development of a Standardized Chemiluminescence Immunoassay for the Detection of Autoantibodies Against Human M-Type Phospholipase A2 Receptor in Primary Membranous Nephropathy

“…The clinical sensitivity of the ChLIA exceeded that of ELISA and RC-IFA by 10.4% and 0.7%, respectively, at similar specificities (>99%). The anti-PLA2R-positive rates detected by ChLIA (83.9%), ELISA (73.5%), and RC-IFA (83.2%) were equal to or higher than the prevalence data determined among non-preselected patients with pMN by different methods, such as Western blot (53.0%-81.7%), 10,11 RC-IFA (48.0-82.3%), 12,13 ELISA (50.0-71.8%), 14,15 addressable laser bead immunoassay (51.5-66.9%), 16,17 luciferase immunoprecipitation systems assay (53.3%), 18 and time-resolved fluoroimmunoassay (71.0-89.7%). 19,20 These variations may be due to differences in assay techniques (e.g., epitope exposure, cutoff values, detected Ig subclass) and cohort characteristics (e.g., ethnicity, immunosuppressive treatment).…”

A Proposal for a Serology-Based Approach to Membranous Nephropathy

“…Although some studies found an association between the degree of proteinuria and PLA2R Ab titer at a defined time point, 30,33,39,40 others found only a weak or no association. 13,22,41 Such variability in association likely reflects the time lag between immunologic and clinical activity, and indeed, a latency period as long as 8 months has been observed between the presence of PLA2R Ab in serum and the first clinical manifestations of MN.…”

“…Others studies found small numbers of positive patients in various groups of secondary MN. 15,[27][28][29][30][31][32][33] The question thus arises whether these patients represent true secondary MN or rather, PLA2R-associated MN with coincident secondary disease. The latter possibility is supported by the following findings in such studies.…”

Clinical observation and analysis of patients with idiopathic membranous nephropathy combined with low 25(OH)D3 levels

“…Newly discovered autoantigens, such as PLA2R [7] and THSD7A [8] , and complement system activation have been found to be involved in the pathogenesis of MN [9] , providing us with a better understanding of the causes of IMN. However, the effects of IMN treatment differ substantially, and many researchers are constantly seeking biological indicators for the disease status and prognosis of IMN.…”