Serum anti-PLA2R antibody and glomerular PLA2R deposition in Chinese patients with membranous nephropathy: A cross-sectional study.
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ABSTRACT:
SUBMITTER: Pang L
PROVIDER: S-EPMC5478356 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
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Serum anti-PLA2R antibody and glomerular PLA2R deposition in Chinese patients with membranous nephropathy: A cross-sectional study.
Pang Lu L Zhang Ai-Min AM Li Hai-Xia HX Du Jia-Lin JL Jiao Li-Li LL Duan Nan N Liu Yi Y Yu Dan D
Medicine 20170601 24
M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated.A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously ...[more]
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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.
| S-EPMC5932148 | biostudies-literature
Project description:Since urine samples more directly reflect kidney alterations and damage than blood samples, we investigated whether urine anti-PLA2R antibody (uPLA2R-Ab) could be utilized similarly to serum anti-PLA2R antibody (sPLA2R-Ab) as a noninvasive biomarker of idiopathic membranous nephropathy (IMN). In this study, we performed a qualitative analysis using an indirect immunofluorescence test (IIFT) and measured uPLA2R-Ab and sPLA2R-Ab concentrations using an enzyme-linked immunosorbent assay (ELISA) in 28 patients with biopsy-proven IMN and 12 patients with secondary membranous nephropathy (SMN). Overall, 64.3% (n=18) of patients with IMN had IIFT-positive sPLA2R-Ab, 67.9% (n=19) of patients with IMN had IIFT-positive uPLA2R-Ab, and none of the SMN patients had IIFT-positive sPLA2R-Ab or uPLA2R-Ab. The titers of the anti-PLA2R antibody from the IMN patients in the urine (10.72±22.24 RU/μmol, presented as uPLA2R-Ab/urine creatinine) and serum (107.36±140.93 RU/ml) were higher than those from the SMN patients (0.51±0.46 RU/μmol, 0.008±0.029 RU/ml, respectively, p<0.05). Statistical analyses indicated that there were positive correlations between uPLA2R-Ab and gPLA2R, sPLA2R-Ab or urinary protein and negative correlations between uPLA2R-Ab and serum albumin in patients with IMN. In conclusion, uPLA2R-Ab is a novel biomarker of IMN. sPLA2R-Ab combined with uPLA2R-Ab might be more helpful for diagnosis and activity in PLA2R associated MN.
| S-EPMC5787499 | biostudies-literature
Project description:BackgroundThe 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.Method328 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.ResultLower 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).ConclusionGAg+/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.
| S-EPMC10566392 | biostudies-literature
Project description:BackgroundSince the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care.MethodsWe conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients' demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference.ResultsMean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml.ConclusionThe anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis.
| S-EPMC9955960 | biostudies-literature
Project description:Background:M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods:A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results:The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P < 0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P = 0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46?g/day, P = 0.015) and serum albumin (23.28 vs. 27.95?g/L, P = 0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08?g/day, P = 0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion:Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.
| S-EPMC7232673 | biostudies-literature
Project description:Primary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was aimed at correlating the serum levels of B cell activators BAFF/BLyS and APRIL with the presence of anti-PLA2R antibodies in PMN patients and with long-term clinical outcome. To this aim, 51 patients with anti-PLA2R-positive biopsy-proven PMN and nephrotic range proteinuria (>3.5 g/24 hours) were enrolled between January 2009 and December 2015 and treated with conventional 6-month immunosuppressive therapy. After 6 months, 29 patients (56.9%) cleared circulating anti-PLA2R, while in remaining 22 (43.1%), they persisted. Intriguingly, in the first group, baseline serum levels of BAFF/BLyS and APRIL were significantly lower than those in the second one. Moreover, after 6 months of immunosuppressive therapy, an overall reduction in both cytokine serum levels was observed. However, in PMN patients with anti-PLA2R clearance, this reduction was more prominent, as compared with those with anti-PLA2R persistence. When related to clinical outcome, lower baseline BAFF/BLyS (<6.05 ng/mL) and APRIL (<4.20 ng/mL) serum levels were associated with significantly higher probability to achieve complete or partial remission after 24-month follow-up. After dividing the entire study cohort into three groups depending on both cytokine baseline serum levels, patients with both BAFF/BLyS and APRIL below the cut-off showed a significantly higher rate of complete or partial remission as compared with patients with only one cytokine above the cut-off, while the composite endpoint was achieved in a very low rate of patients with both cytokines above the cut-off. Taken together, these results provide new insights into the role of BAFF/BLyS and APRIL in both the pathogenesis of anti-PLA2R-positive PMN and the response to immunosuppressive therapy.
| S-EPMC6874868 | biostudies-literature
Project description:Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.
| S-EPMC3148709 | biostudies-literature
Project description:BackgroundThe diagnostic value of serum M-type phospholipase A2 receptor antibody (sPLA2R-ab) expression in patients with primary membranous nephropathy (PMN) has been established. However, the association between sPLA2R-ab and clinical remission remains uncertain.MethodsWe systematically searched the literature for clinical trials regarding the correlation between sPLA2R-ab expression and clinical remission of PMN patients. Meta-analysis was performed to determine this association. Subgroup analysis, funnel plots, and sensitivity analysis were also performed to investigate heterogeneity or bias.ResultsA total of 11 trials involving 824 patients were included. Patients with positive sPLA2R-ab had a poor clinical remission rate (RR?=?0.76, 95%CI 0.68-0.86, P?<?0.0001; I2?=?39%), a higher titer of sPLA2R-ab had a lower chance of clinical remission (RR?=?0.72, 95%CI 0.59-0.87, P?=?0.0006; I2?=?42%),and a higher risk of renal failure (RR?=?4.85, 95% CI, 1.83-12.85, P?=?0.002; I2?=?0%), without affecting relapse (RR?=?0.97, 95% CI, 0.55-1.70; P?=?0.92, I2?=?0%). Subgroup analysis by treatment strategies, assay methods, ethnicity, gender, renal function, the approach of ruling out SMN, and the ratio of patients with nephrotic-range proteinuria at baseline showed no significant association between these factors with the prognostic value of sPLA2R-ab for PMN patients. No significant publication bias was found.ConclusionThis meta-analysis adds to the evidence for current guidelines that sPLA2R-ab acts as not only a diagnostic marker but also a pivotal predictor for clinical remission. Therefore, sPLA2R-ab can be considered as a prognostic factor for stratifying PMN patients.
| S-EPMC6749720 | biostudies-literature
Project description:BackgroundSerum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans.MethodsThis was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated.ResultsOf the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32).ConclusionGlomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.
| S-EPMC7791976 | biostudies-literature
Project description:BackgroundThe aim of this study was to investigate the correlation between the phospholipase A2 receptor (PLA2R) gene polymorphism and idiopathic membranous nephropathy (IMN) in Heilongjiang Chinese.MethodsThirty-five patients with IMN confirmed by renal biopsy attending the Heilongjiang Hospital of Traditional Chinese Medicine between June 2021 and December of 2021 were selected as the IMN group, and a group of 25 healthy participants from the Physical Examination Center of Heilongjiang Hospital of Traditional Chinese Medicine were enrolled as healthy controls. Polymerase chain reaction (PCR) was used to identify and genotype 8 single-nucleotide polymorphism (SNP) loci (rs16844715, rs2715918, rs2715928, rs35771982, rs3749119, rs3828323, rs4665143, and rs6757188) of PLA2R and to analyze the PLA2R gene polymorphisms that correlated with IMN. SPSS 26.0 statistical software was used for data analysis, and the chi-squared (χ2) goodness-of-fit test was used to determine whether each SNP genotype and allele in the PLA2R gene complied with the Hardy-Weinberg equilibrium. The qualitative data were analyzed via χ2 or Fisher exact probability method. Logistic regression was used to analyze risk factors, and the odds ratios (ORs) values and 95% confidence intervals (CIs) were calculated. α=0.05 was taken as the test level, and P<0.05 was considered statistically significant.ResultsStatistically significant differences were found in the genotype and allele frequencies of rs35771982 and rs3749119 between the IMN and control groups (P<0.05). Logistic regression analysis showed that the genotypes rs35771982 GG and rs3749119 CC were associated with IMN susceptibility. Statistically significant differences in uric acid level were found between the rs35771982 GG and CG + CC genotypes (P<0.05), while statistically significant differences in serum albumin were detected between rs3749119 CC and the CT + TT genotypes (P<0.05). Multivariate logistic regression analysis showed that gender, age, and triglyceride levels affected the occurrence of IMN (P<0.05).ConclusionsThe PLA2R gene polymorphisms rs35771982 and rs3749119 in Heilongjiang Chinese may be related to IMN susceptibility and correlated with clinical indicators of IMN. Gender, age, and triglyceride levels may influence the occurrence of IMN.
| S-EPMC9951016 | biostudies-literature