Serum phospholipase A2 receptor antibodies and immunoglobulin G subtypes in adult idiopathic membranous nephropathy: Clinical value assessment

Cheng, Genyang; Liu, Jianhua; Akankwasa, Gilbert; Cao, Yun; An, Changjuan; Lv, Zhe; Wang, Chen; Nie, Ruili; Jin, Zhang; Liu, Yong; Xia, Meng; Li, Shijun; Cai, Hong; Li, Yongzhe; Qin, Xiaosong

doi:10.1016/j.cca.2018.12.027

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…At present, the detection of sera anti-PLA2R antibodies normally applies indirect immunofluorescence assay (IIFA) and enzyme-linked immunosorbent assay (ELISA) [ 11 ]. IIFA is not a quantitative detection measure, while ELISA is characterized by low detection sensitivity [ 12 ]. In 2017, Huang et al [ 13 ] developed an ultrasensitive quantitative assay, using time-resolved fluoroimmunoassay (TRFIA), for the detection of anti-PLA2R-IgG testing.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Xue

Guo

et al. 2021

Journal of Healthcare Engineering

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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.

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Section: Introductionmentioning

confidence: 99%

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

Liu

Xue

Guo

et al. 2021

Journal of Healthcare Engineering

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“…Human IgG can be divided into IgG1, IgG2, IgG3, and IgG4 subclasses, wherein IgG4 corresponds to anaphylactogen as the least abundant in plasma. However, anti-PLA2R IgG4 is predominant, followed by IgG1, IgG3, and IgG2, in IMN [ 9 , 19 ]. With accurate quantification of PLA2R antibodies, the ratio was significantly higher in the PLA2R-positive group, which indicated that IgG4 was the main subclass of PLA2R antibodies and could injure the glomeruli by recognizing the PLA2R antigen.…”

Section: Discussionmentioning

confidence: 99%

“…The decreasing ratio in remission patients proved that IgG4 was not consistently dominant in all pathological stages, suggesting that the IgG1-3 subclasses participated in the remission process. This finding may explain the different proportions of serum IgG1-3 subtypes in IMN patients from another side [ 19 ]. More studies are needed on IgG1-3 anti-PLA2R to elucidate the physiopathologic mechanism of IMN.…”

Section: Discussionmentioning

confidence: 99%

Clinical Evaluation of Antiphospholipase A2 Receptor IgG4 level and Its IgG4‐to‐IgG Ratio Based on Quantitative Immunoassays in Idiopathic Membranous Nephropathy

Zhang

Huang

et al. 2022

BioMed Research International

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Background. Phospholipase A2 receptor (PLA2R), located at the membrane of glomerular podocyte, is the major autoantigen of idiopathic membranous nephropathy (IMN), and its antibodies with a predominant IgG4 subclass lead to pathological lesions. Further studies could be performed to validate the clinical values of PLA2R-IgG, PLA2R-IgG4, and PLA2R-IgG4-to-IgG ratios, as ultrasensitive and quantitative immunoassays for PLA2R antibodies have been well established in our previous work. Methods. A cohort of 58 IMN patients, 30 of whom were followed from 3 to 42 months, was assessed for serum PLA2R-IgG and -IgG4 levels, and the ratio of PLA2R-IgG4/-IgG combined with relative clinicopathological indicators. Results. Serum PLA2R-IgG4 level was significantly correlated with glomerular PLA2R staining. In addition, it was strongly correlated with PLA2R-IgG and its ratio. PLA2R-IgG and -IgG4 levels were both correlated with high-density lipoprotein and erythrocyte sedimentation rates. The ratio at the first diagnosis can predict the remission, and its efficacy overmatched PLA2R-IgG4. In the survival curves, negative results for the ratio or PLA2R-IgG4 at the first diagnosis demonstrated higher remission rates. Conclusion. Serum PLA2R-IgG4 concentration may replace renal PLA2R immunohistochemistry in IMN diagnosis. We propose that the PLA2R-IgG4-to-IgG ratio and PLA2R-IgG4 could be novel indicators for remission prediction in clinical practice.

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“…The detection of anti-PLA2R and anti-THSD7A antibodies by commercial immunofluorescence direct assay represents high specificity and sensitivity [46]. Currently, available commercial anti-PLA2R antibodies immunoenzymatical method (ELISA) represents high specificity (100%) but lower sensitivity (69.9%) [69]. The negative value of 2.7 RU/ml based on receiver operating characteristic curves (retrospective analysis of 67 consecutive patients naive of immunosuppression) increases the sensitivity and specificity to 88.1 and 96%, respectively [70].…”

Section: Anti-phospholipase A2 Receptor and Anti-thrombospondin Domain 7a Antibodies: Serological Detection Methodsmentioning

confidence: 99%

Molecular classification of membranous nephropathy

Pozdzik

Touzani

Brochériou

et al. 2019

Current Opinion in Nephrology and Hypertension

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Purpose of review Continuous expansion of our knowledge in the pathogenesis of membranous nephropathy possible by the identification of antibodies recognized specific podocytes antigens results in unprecedent patient management strategy. Recent findingsCirculating anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin domain 7A (THSD7A) antibodies strongly relate with the modifications of podocytes biology leading to the new molecular diagnosis of membranous nephropathy. Immunization against THSD7A involves extra-renal mechanism. However, the pathway of anti-PLA2R immunization still remains unresolved. Experimental data highlight the crucial role of THSD7A in the attachment of podocytes to the glomerular basement membrane, rewarding the THSD7A pathogenicity, whereas the third of Koch's postulates is still not fulfilled for anti-PLA2R antibodies. The anti-PLA2R antibodies epitope spreading will possibly be even more specific marker improving the molecular classification of membranous nephropathy. Two immune epitopes have been identified in the N-terminal tail of THSD7A but without evidence of epitope spreading as for anti-PLA2R.

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Serum phospholipase A2 receptor antibodies and immunoglobulin G subtypes in adult idiopathic membranous nephropathy: Clinical value assessment

Cited by 8 publications

References 24 publications

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

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

Clinical Evaluation of Antiphospholipase A2 Receptor IgG4 level and Its IgG4‐to‐IgG Ratio Based on Quantitative Immunoassays in Idiopathic Membranous Nephropathy

Molecular classification of membranous nephropathy

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