Dataset Information

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

ABSTRACT:

Background

The application of podocyte antigen M-type phospholipase A2 receptor (PLA2R, GAg) and serum anti-PLA2R antibody (SAb) in predicting the prognosis of membrane nephropathy (MN) was controversial.

Method

328 biopsy-proven MN patients were divided into three phenotypes, 182 MN patients with GAg+/SAb+, 118 MN patients with GAg+/SAb-, and 28 MN patients with GAg-/SAb-. The baseline clinicopathological characteristics, therapy response, and prognosis were compared among the three groups. Cox regression analysis was performed to assess predictors of remission. Anti-PLA2R antibody was analyzed by receiver operating characteristic curve to find the optimal titer for MN diagnosis.

Result

Lower eGFR (p = 0.009), higher UPCR (p < 0.001), and lower serum albumin (p < 0.001) were observed in GAg+/SAb+ MN patients, compared to GAg+/SAb- MN patients. More GAg+/SAb+ MN patients received cyclophosphamide (CTX) combined with glucocorticoids and calcineurin inhibitors (CNI) based therapy than the other two groups (p = 0.015 and p = 0.023, respectively). No significant difference was observed among the three groups in terms of complete remission, relapse, and developing ESRD. SAb+ status was an independent predictor for no remission (hazard ratio 1.378, 95% confidence interval 1.023 to 1.855; p = 0.035). The optimal cutoff value for anti-PLA2R antibody to predict MN was 2.055 RU/mL (sensibility 0.802, specificity 0.970).

Conclusion

GAg+/SAb+ MN patients were related to more severe clinical manifestations and more requisition of immunosuppressive treatment. Positive anti-PLA2R antibody was an independent predictor for no remission. An anti-PLA2R antibody above 2.055 RU/mL can be a suggestive indicator of MN diagnosis in patients with proteinuria.

SUBMITTER: Chen Y

PROVIDER: S-EPMC10566392 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

Chen Yang Y Xu Ying Y Chen Siyu S Yu Yedong Y Zhu Xueling X Chen Jianghua J

Renal failure 20231009 2

<h4>Background</h4>The application of podocyte antigen M-type phospholipase A2 receptor (PLA2R, GAg) and serum anti-PLA2R antibody (SAb) in predicting the prognosis of membrane nephropathy (MN) was controversial.<h4>Method</h4>328 biopsy-proven MN patients were divided into three phenotypes, 182 MN patients with GAg+/SAb+, 118 MN patients with GAg+/SAb-, and 28 MN patients with GAg-/SAb-. The baseline clinicopathological characteristics, therapy response, and prognosis were compared among the th ...[more]

PMID: 37814415

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Project description:BackgroundM-type phospholipase A2 receptor (PLA2R) is known as a major antigen on podocytes, which is involved with the pathogenesis of idiopathic membranous nephropathy (iMN). Many studies have shown that serum anti-PLA2R autoantibodies (sPLA2R) are prevalent in patients with iMN but are rarely detected in secondary membranous nephropathy (SMN) or other glomerulonephritis. The anti-PLA2R is considered as a promising serum biomarker in iMN but reports about its diagnostic value are variable and inconsistent.ObjectiveTo evaluate the diagnostic test accuracy (DTA) of anti-PLA2R and glomerular PLA2R antigen (gPLA2R) for diagnosing iMN.MethodMEDLINE, EMBASE, WEB OF SCIENCE, and COCHRANE LIBRARY were searched from 2009 January to February 2018. Heterogeneity was evaluated by Q test and I2. Source of heterogeneity was explored by subgroup analysis and meta-regression. Meta-analysis was executed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.ResultsTotally, 35 studies were retrieved under the pre-set study eligibility criteria. Twenty-eight studies were included to evaluate the DTA of anti-PLA2R for differentiating iMN from non-iMN. They indicated a pooled sensitivity of 65% (63-67%), specificity of 97% (97-98%), positive likelihood ratio of 15.65 (9.95-24.62), and negative likelihood ratio of 0.37 (0.32-0.42) with a diagnostic OR (sDOR) of 50.41 (31.56 to 80.52) and AUC of 0.9393. No threshold effect was detected. The heterogeneity analysis for sDOR showed that I2 = 50.3% and Cochran-Q = 54.29, df = 27 (p = 0.0014). Heterogeneity was significant. Meta-regression revealed that sample size might be the potential source of heterogeneity. Subgroup analysis demonstrated that method type and ratio of patients with nephrotic-range proteinuria at baseline might be the source of heterogeneity. Sixteen studies reported the diagnostic value of glomerular PLA2R antigen for differentiating iMN from non-iMN. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, sDOR, and AUC were 79% (76-81%), 90% (88-92%), 8.17 (5.60-11.93), 0.25 (0.19-0.33), 39.37 (22.18-60.13), and 0.9278. Heterogeneity analysis showed that Cochran-Q = 35.36; df = 15 (p = 0.002), and I2 for sDOR was 57.6%.ConclusionsPLA2R and gPLA2R demonstrated a good diagnostic accuracy in differentiating iMN and non-iMN.

Project description:IntroductionClinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers.MethodsIn this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status.ResultsEighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria.ConclusionAssessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.

Dataset Information

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

Background

Method

Result

Conclusion

Publications

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

Similar Datasets

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