Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study

Kezhi Zhou, Junyi Zhou, Leting Zhou, Jing Xue, Bin Liu, Zhijian Zhang, Xiran Zhang, Ting Cai, Sijia Shao, Biao Huang, Yi Zhang, Zhigang Hu, Liang Wang and Xiaobin Liu

PLOS ONE, 2024, vol. 19, issue 5, 1-18

Abstract: Background: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. Methods: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. Results: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26–0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62–0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601–0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587–0.824), thus, demonstrating robustness. Conclusions: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0302100

DOI: 10.1371/journal.pone.0302100

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