A PLA2R-IgG4 Antibody-Based Predictive Model for Assessing Risk Stratification of Idiopathic Membranous Nephropathy

Abstract

Background. Known as an autoimmune glomerular disease, idiopathic membranous nephropathy (IMN) is considered to be associated with phospholipase A2 receptor (PLA2R) in terms of the main pathogenesis. The quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies by time-resolved fluoroimmunoassay (TRFIA) was determined, and the value of them, both in the clinical prediction of risk stratification in IMN, was observed in this study. Methods. 95 patients with IMN proved by renal biopsy were enrolled, who had tested positive for serum PLA2R antibodies by ELISA, and the quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies was achieved by TRFIA. All the patients were divided into low-, medium-, and high-risk groups, respectively, which were set as dependent variables, according to proteinuria and renal function. Random forest (RF) was used to estimate the value of serum PLA2R-IgG and PLA2R-IgG4 in predicting the risk stratification of progression in IMN. Results. Out-of-bag estimates of variable importance in RF were employed to evaluate the impact of each input variable on the final classification accuracy. The variable of albumin, PLA2R-IgG, and PLA2R-IgG4 had high values (>0.3) of 0.3156, 0.3981, and 0.7682, respectively, which meant that these three were more important for the risk stratification of progression in IMN. In order to further assess the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we built four different models and found that PLA2R-IgG4 played an important role in improving the predictive ability of the model. Conclusions. In this study, we established a random forest model to evaluate the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN.

PLA2R-IgG4 antibody as a predictive biomarker of treatment effectiveness and prognostic evaluation in patients with idiopathic membranous nephropathy: a retrospective study

“…Although there were just 35.1% and 21.1% of patients achieved remission at the 6th month, remission rates were significantly increased at the end of the observational phase (64.9% vs 34.2%) ( Dahan et al, 2017 ), indicating that PLA2R antibody levels precede the clinical remission and predict clinical response. Moreover, our previous study found that the efficacy of PLA2R-IgG4 in the diagnosis and risk stratification of IMN was better than that of PLA2R-igG ( Huang et al, 2019 ; Liu et al, 2021 ). On the basis of previous work, this study made a preliminary exploration on the clinical efficacy of PLA2R-igG and PLA2R-IgG4 in the prognosis analysis.…”

“… Huang et al (2019) made a further improvement on the sensitivity to 90% by investigating PLA2R-IgG4 titer by TRFIA. Liu et al (2021) demonstrated that PLA2R-IgG4 was a more efficient biomarker in predicting the risk of progression in IMN, compared with anti-PLA2R-IgG.…”

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy

“…IMN can be clinically diagnosed and monitored by testing for PLA2R [ 12 ]. Among them, PLA2R-IgG4 antibody is considered to be the most valuable for stratifying the risk of IMN [ 13 ]. In recent years, the number of studies focusing on PLA2R has gradually increased.…”

A dynamic online nomogram for predicting renal outcomes of idiopathic membranous nephropathy

“…It is well documented that PLA2R and its autoantibodies are closely related to the prognosis of IMN [45][46][47] . Compared with glomerular PLA2R deposition, serum anti-PLA2R antibody levels are more closely correlated with renal outcome [46] .…”