Serum Phospholipase A2 Receptor Antibody Research Articles

An Updated Review of Membranous Nephropathy.

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor (PLA2R) as a target antigen has led to a paradigm shift in the understanding and management of MN. At present, serum PLA2R antibodies are used for diagnosis, prognostication, and guiding treatment. Now, with the discovery of more than 20 novel target antigens, antigen mapping is almost complete. The clinical association of certain antigens provides clues for clinicians, such as the association of nerve epidermal growth factor-like 1 with malignancies and indigenous medicines. Serum antibodies are detected for most target antigens, except exostosin 1 and 2 and transforming growth factor-beta receptor 3, but their clinical utility is yet to be defined. Genome-wide association studies and studies investigating environmental factors, such as air pollution, shed more light on the underpinnings of MN. The standard therapy of MN diversified from cyclical cyclophosphamide and steroids to include rituximab and calcineurin inhibitors over the past decades. Here, we provide a cutting-edge review of MN, focusing on genetics, immune system and environmental factors, novel target antigens and their clinical characteristics, and currently available and emerging novel therapies in MN.

PLA2R-positive membranous nephropathy in IgG4-related disease

BackgroundIgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases.Case presentationHerein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R.The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy.ConclusionsNephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Clinical Observation of Serum Anti-PLA2R Antibody Levels in the Treatment of Idiopathic Membranous Nephropathy with Rituximab

Objective: To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy with varying levels of serum phospholipase A2 receptor antibodies. Methods: A total of 137 patients with idiopathic membranous nephropathy admitted to Beijing Sixth Hospital were selected. Based on their blood PLA2R antibody levels before rituximab treatment, patients were categorized into the PLA2R antibody positive group (n = 94) and the PLA2R antibody negative group (n = 43). They were followed up for at least 1 year, during which the efficacy, measured through 24-hour urine protein quantification and serum albumin levels, were compared between the two groups before and after treatment. Results: After 3 months of treatment, there was no significant difference in the quantitative levels of 24-hour urine protein between the two groups (P > 0.05). However, after 6 and 12 months of treatment, there was a significant difference in the levels of 24-hour urine protein between the two groups (P < 0.05). Additionally, after 3 months of treatment, there was a notable difference in the serum albumin levels between the two groups (P < 0.05). However, after 6 and 12 months of treatment, there was no significant difference in serum albumin levels between the two groups (P > 0.05). Analysis of complications in the two groups revealed that in the positive group, 9 individuals experienced thrombosis, 5 had infections, and 11 developed acute kidney injury (AKI). In contrast, in the negative group, 5 individuals had thrombosis, 2 had infections, and 3 developed AKI. There was no statistically significant difference in complications between the two groups (P > 0.05). Conclusion: Serum anti-PLA2R antibody levels provide valuable insights into the clinical observation of rituximab treatment for idiopathic membranous nephropathy. They aid in understanding the disease’s pathogenesis, evaluating treatment efficacy, and predicting disease prognosis.

Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies

Background Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb−) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. Methods A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan–Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb−/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. Results Among 74 IMN patients, 14 were SAb−/GAg+. Compared with SAb+/GAg + patients, SAb−/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p < .01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66–0.95], p = .01) and high cholesterol (1.81 [95%CI: 1.02–3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb−/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb−/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01–18.17], p = .04). Conclusion IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.

Serum PLA2R antibody as a predictive biomarker for venous thromboembolism risk in primary membranous nephropathy

BackgroundPatients with nephrotic syndrome are at high risk of venous thromboembolism (VTE), especially for primary membranous nephropathy (PMN). The phospholipase A2 receptor (PLA2R) is a marker of primary membranous nephropathy activity. This study investigated the predictive value of PLA2R antibodies in PMN for VTE. MethodsIn this retrospective study, we included 97 PMN patients and evaluated the predictive value of serum PLA2R antibodies for VTE risk. Lower extremity venous ultrasound, renal vein ultrasound, or spiral computed tomography pulmonary arteriography were used to assess VTE events. Serum anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The risk of VTE was stratified according to serum albumin levels. ResultsTwenty PMN patients (21%) had thromboembolic events. Eight (15%) of patients with serum albumin >25g/l developed VTE, 6 of whom were positive for serum PLA2R antibodies. Positive serum PLA2R antibodies were significantly associated with VTE events in patients with serum albumin >25g/l (p=0.01). Age, sex, blood creatinine, serum albumin, and 24-h urine protein levels were not statistically different between the two groups. Kaplan–Meier analysis using the log-rank test revealed anti-PLA2R positive membranous nephropathy patients had more probability of VTE events than anti-PLA2R negative patients. Univariate Cox proportional hazards analysis revealed that lnPLA2R-Ab is an unfavorable predictor for VTE events in patients with serum albumin >25g/l (hazard ratio (HR) 2.1, p=0.01). ConclusionsThe PLA2R antibody was a risk predictor for thromboembolic events in patients with primary membranous nephropathy with serum albumin >25g/l.

Novel Antigens and Clinical Updates in Membranous Nephropathy.

Membranous nephropathy (MN), an autoimmune kidney disease and leading cause of nephrotic syndrome, leads to kidney failure in up to one-third of affected individuals. Most MN cases are due to an autoimmune reaction against the phospholipase A2 receptor (PLA2R) located on kidney podocytes. Serum PLA2R antibody quantification is now part of routine clinical practice because antibody titers correlate with disease activity and treatment response. Recent advances in target antigen detection have led to the discovery of more than 20 other podocyte antigens, yet the clinical impact of additional antigen detection remains unknown and is under active investigation. Here we review recent findings and hypothesize how current research will inform future care of patients with MN.

Serum PLA2R antibody as a predictive biomarker for venous thromboembolism risk in primary membranous nephropathy

BackgroundPatients with nephrotic syndrome are at high risk of venous thromboembolism (VTE), especially for primary membranous nephropathy (PMN). The phospholipase A2 receptor (PLA2R) is a marker of primary membranous nephropathy activity. This study investigated the predictive value of PLA2R antibodies in PMN for VTE. MethodsIn this retrospective study, we included 97 PMN patients and evaluated the predictive value of serum PLA2R antibodies for VTE risk. Lower extremity venous ultrasound, renal vein ultrasound, or spiral computed tomography pulmonary arteriography were used to assess VTE events. Serum anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The risk of VTE was stratified according to serum albumin levels. ResultsTwenty PMN patients (21%) had thromboembolic events. Eight (15%) of patients with serum albumin >25g/l developed VTE, 6 of whom were positive for serum PLA2R antibodies. Positive serum PLA2R antibodies were significantly associated with VTE events in patients with serum albumin >25g/l (p=0.01). Age, sex, blood creatinine, serum albumin, and 24-h urine protein levels were not statistically different between the two groups. Kaplan–Meier analysis using the log-rank test revealed anti-PLA2R positive membranous nephropathy patients had more probability of VTE events than anti-PLA2R negative patients. Univariate Cox proportional hazards analysis revealed that lnPLA2R-Ab is an unfavorable predictor for VTE events in patients with serum albumin >25g/l (hazard ratio (HR) 2.1, p=0.01). ConclusionsThe PLA2R antibody was a risk predictor for thromboembolic events in patients with primary membranous nephropathy with serum albumin >25g/l.

The Sensitivity and Specificity of Serum Phospholipase A2 Receptor Antibodies in Diagnosing Primary Membranous Nephropathy in Patients with Adult Nephrotic Syndrome and its Correlation with Serum Phospholipase A2 Receptor Staining in Kidney Biopsies

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in nondiabetic adults, with about 70%–80% of cases of MN being primary MN (pMN). Many studies have shown that serum phospholipase A2 receptor (PLA2R) antibodies are a diagnostic and prognostic biomarker for pMN, with a pooled diagnostic sensitivity and specificity of 54%–82% and 89%–100%, respectively, resulting in PLA2R staining and serum PLA2R antibodies being incorporated in the management algorithms of MN. We studied the sensitivity and specificity of serum PLA2R antibodies for diagnosing pMN and its correlation with PLA2R staining in kidney biopsies in a prospective observational study of 58 adult NS subjects undergoing a kidney biopsy. Serum PLA2R antibodies were determined by indirect immunofluorescence (IF) before the biopsy. Kidney biopsies were sent for light microscopy and IF examinations. Biopsy samples with MN histology were stained for PLA2R antigens. Out of the 58 adult NS subjects, 28 were diagnosed with pMN and one with secondary MN. Serum PLA2R antibodies were positive in 12 subjects with pMN, and one had focal segmental glomerulosclerosis not otherwise specified, giving a sensitivity of 42.8% and specificity of 96.7% for diagnosing pMN. There was a significant association between glomerular staining for PLA2R (24 of 28 subjects) and a diagnosis of pMN by kidney biopsy, with a sensitivity of 82.8%. Cohen's kappa agreement between glomerular staining for PLA2R and a diagnosis of MN was 0.83 (0.57–1.08).

New-Onset and Relapsed Membranous Nephropathy post SARS-CoV-2 and COVID-19 Vaccination.

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and COVID-19 vaccination, new-onset and relapsed clinical cases of membranous nephropathy (MN) have been reported. However, their clinical characteristics and pathogenesis remained unclear. In this article, we collected five cases of MN associated with SARS-CoV-2 infection and 37 related to COVID-19 vaccination. Of these five cases, four (4/5, 80%) had acute kidney injury (AKI) at disease onset. Phospholipase A2 receptor (PLA2R) in kidney tissue was negative in three (3/5, 60%) patients, and no deposition of virus particles was measured among all patients. Conventional immunosuppressive drugs could induce disease remission. The underlying pathogenesis included the subepithelial deposition of viral antigens and aberrant immune response. New-onset and relapsed MN after COVID-19 vaccination generally occurred within two weeks after the second dose of vaccine. Almost 27% of patients (10/37) suffered from AKI. In total, 11 of 14 cases showed positive for PLA2R, and 20 of 26 (76.9%) presented with an elevated serum phospholipase A2 receptor antibody (PLA2R-Ab), in which 8 cases exceeded 50 RU/mL. Conventional immunosuppressive medications combined with rituximab were found more beneficial to disease remission for relapsed patients. In contrast, new-onset patients responded to conservative treatment. Overall, most patients (24/37, 64.9%) had a favorable prognosis. Cross immunity and enhanced immune response might contribute to explaining the mechanisms of MN post COVID-19 vaccination.

GDF-15 and sST-2 act as biomarkers of disease severity but not independent predictors in idiopathic membranous nephropathy

BackgroundWe aimed to explore biomarkers of disease severity in idiopathic membranous nephropathy (IMN) and independent predictors of prognosis in IMN. MethodsClinical data were collected from 79 IMN patients. Serum levels of growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity (sST-2) were tested by enzyme-linked immunosorbent assay (ELISA) in IMN patients and subgroups, and correlation analysis was performed. Univariate and multiple logistic regression analyses were performed to identify independent predictors of IMN, and a combined-factors model was constructed. Moreover, the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prognostic efficacy. ResultsThe levels of GDF-15 were significantly higher in the IMN group and subgroups with low estimated glomerular filtration rate (eGFR) and high 24 hour-urine protein (24 h-UP), whiles sST-2 level was only significantly higher in the IMN group. GDF-15 levels were positively correlated with creatinine (Crea), cystatin C (Cys-C) and 24 h-UP and negatively correlated with GFR and albumin (Alb), while sST-2 levels were positively correlated with Urea and Cys-C and negatively correlated with eGFR. After one year of follow-up, 54 patients had incomplete remission. Serum phospholipase A2 receptor antibody (PLA2R-Ab), Urea, high-density lipoprotein cholesterol (HDL-C) and 24 h-UP but not GDF-15 and sST2 were independent predictors of prognosis in IMN patients, but combined factors showed the best prognostic efficacy. ConclusionSerum levels of GDF-15 and sST-2 may be potential biomarkers for the severity of IMN, while the combined-factors model is effective for predicting the risk factors of incomplete remission in IMN.

The correlation between Serum phospholipase A2 receptor antibody and clinicopathological features in patients with membranous nephropathy

Objective: To assess the correlation between Serum phospholipase A2 receptor antibody and clinicopathological features in patients with membranous nephropathy. Method: The patients being hospitalized for renal biopsy were selected in this study from January 2016 to January 2018. And normal controls were randomly selected; all the patients were divided into idiopathic membranous nephropathy and non-idiopathic membranous nephropathy groups; patients with idiopathic membranous nephropathy were divided into three groups, namely stage I, stage II and stage III; using software for statistical analysis. Results: A total of 357 patients were enrolled, including 155 patients with idiopathic membranous nephropathy, 183 patients with non-idiopathic membranous nephropathy, and 19 cases for normal controls. The average age of the idiopathic membranous nephropathy (IMN) group is higher than that of the membranous nephropathy group (P = 0.01). Different pathological stages of idiopathic membranous nephropathy general clinical characteristics analysis results showed that the age, cys c, serum creatinine (Scr) in stage III membranous nephropathy group were higher than those of the stage I and II membranous nephropathy (P values were 0.003, 0.000 and 0.000 respectively); titers of serum phospholipase A2 receptors antibody with stage II and III membranous nephropathy higher than the stage I membranous nephropathy group (P = 0.006); serum albumin (Alb) levels correlated inversely with serum anti-PLA2R antibody titers (rs = –0.234, P = 0.003), serum antiphospholipase A2 receptor (PLA2R) antibody titer level in patients with idiopathic membranous nephropathy was significantly higher than that in patients with non-membranous nephropathy (P &lt; 0.001). Conclusion: Baseline titer of serum anti-PLA2R antibody is negatively correlated with Alb in the IMN patients，and serum anti-PLA2R antibody level in patients with stage I IMN was significantly lower than stage II and III IMN patients.

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

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.

Treatment preferences for primary membranous nephropathy: Results of a multinational survey among nephrologists in the South Asia Pacific region.

There is no clear consensus on how best to treat primary membranous nephropathy (PMN). This study aimed to ascertain prevailing views among nephrologists on their choice of immunosuppressive agents to treat this disease. The Australasian Kidney Trials Network conducted a multinational online survey among nephrologists from the South Asia-Pacific region to identify prescribing practices to treat PMN. Survey questions focused on the types of immunosuppressive therapies used, preferred first-line and second-line therapies, indications for starting immunosuppressive therapy, the preferred mode of combining corticosteroid and cyclophosphamide, the use of serum phospholipase A2 receptor antibody testing in clinical practice, indications for anticoagulation, and interest in participating in future clinical trials in PMN. One hundered fifty-five nephrologists from eight countries responded to the online survey. The majority of them were senior nephrologists from Australia and India with significant experience managing patients with PMN. The combination of cyclophosphamide and corticosteroid was the preferred first-line therapy. Of those who used this combination, only 34.8% followed the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines by adding intravenous methylprednisolone. The combination of calcineurin inhibitor with corticosteroid was the most common second-line therapy. Most respondents considered prophylactic anticoagulation if serum albumin was less than 25 g/L. Most nephrologists were keen to participate in a clinical trial with a control arm consisting of cyclophosphamide and corticosteroids. The combination of corticosteroid with cyclophosphamide (without intravenous methylprednisolone) is the most commonly reported first-line immunosuppressive therapy for the management of PMN.

MO281THE EVALUATION OF TEST EFFICIENCY ON LOW TITER SERUM PHOSPHOLIPASE A2 RECEPTOR ANTIBODY

Abstract Background and Aims Antibody to phospholipase A2 receptor (PLA2R) was widely detected for a decade as a diagnostic marker of idiopathic membranous nephropathy. Recently, several studies reported that a lower cut-off of serum PLA2R antibody (PLA2RsAb) could improve diagnostic efficacy. The recommend cut-off ranged from 2.0 to 2.7 RU/ml which was considered largely improving the sensitivity of the assay. Other reported that although sensitivity of the measurement might loss to some extent cut-off at 14 RU/ml might of the best clinical performance. However, the lower cut-off was slightly higher than the minimum detection limit, that was 2.0 RU/ml. There was no study evaluated the test efficiency of low titer antibody of the measurement. Method The reference range of PLA2RsAb was validated by testing 40 serum from health volunteer, male/female ratio was 20/20. The samples for intra and inter-batch precision test were prepared by mixing low titer PLA2RsAb serum. The intra-batch precision was performed by repeating six times of the validation sample in one plate. The inter-batch precision was performed by repeating four times of validation samples in one plate on five days. Results The medium age of male was 34 (31, 53) and 46 (31, 54) for female, respectively. PLA2RsAb was ranged from 2.0 to 4.3 RU/ml for male and 2.0 to 4.0 RU/ml for female. The average of intra-batch validation sample was 8.1 ± 1.2 RU/ml. The intra-batch precision was presented by coefficient of variation, that was 15%. The average of inter-batch validation samples were 4.0 ± 0.4 RU/ml and 5.2 ± 0.5 RU/ml, respectively. The inter-batch precision was 10% for both validation serum. Conclusion Healthy population showed low titer PLA2RsAb positive according to a lower cut-off. The validation showed relative high coefficient of variation on intra and inter-batch precision of low titer PLA2RsAb.

Seropositive PLA2R-associated membranous nephropathy but biopsy-negative PLA2R staining.

Serum phospholipase A2 receptor (PLA2R) antibody (SAb) and glomerular deposits of PLA2R antigen (GAg) have been tested widely in idiopathic membranous nephropathy (MN). Recently, we noticed a special form of PLA2R-associated MN with positive circulating PLA2R antibody but negative PLA2R deposits in the glomeruli by immunofluorescence on frozen tissue (IF-F). The significance of this form of PLA2R-associated MN is yet to be elucidated. This study aimed to explore the clinicopathological features of these PLA2R-associated MN patients. This study enrolled 229 biopsy-proven PLA2R-associated MN patients with SAb+. SAb was measured by enzyme-linked immunosorbent assay, and GAg was detected by IF-F. These patients were divided into SAb+/GAg+ and SAb+/GAg- groups. Clinicopathological characteristics of SAb+/GAg+ and SAb+/GAg- PLA2R-associated MN patients were compared. PLA2R antigens of 19 SAb+/GAg- PLA2R-associated MN patients were verified by immunohistochemistry on paraffin tissue (IHC-P). Among 229 SAb+ PLA2R-associated MN patients, 210 (91.70%) were GAg+ and 19 (8.3%) were GAg-. These 19 SAb+/GAg- PLA2R-associated MN patients presented positive PLA2R deposits by IHC-P. Compared with SAb+/GAg+ PLA2R-associated MN patients, SAb+/GAg- PLA2R-associated MN patients had higher levels of serum PLA2R antibody (P = 0.004), increased proteinuria (P = 0.008), lower serum albumin (P = 0.019), more prominent chronic pathological lesions in terms of glomerulosclerosis score (P = 0.025), interstitial fibrosis score (P = 0.016), tubular atrophy score (P = 0.010) and total renal chronicity score (P = 0.010), and were more likely to be accompanied by focal segmental glomerulosclerosis (P = 0.014). Higher SAb level was associated with the total renal chronicity score (odds ratio per 100 RU/mL, 1.16; 95% confidence interval 1.01-1.33; P = 0.033). PLA2R-associated MN patients with seropositive PLA2R antibody but negative PLA2R deposits in the glomeruli by IF-F have higher levels of SAb and worse clinicopathological manifestations compared with their double-positive counterparts. IHC-P can be an alternative technique to reveal PLA2R glomerular deposits.

Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A2 receptor (PLA2R) on frozen renal biopsy with the presence of detectable serum PLA2R antibody assessed by enzyme linked immunosorbent assay (ELISA) in the diagnosis of primary MGN. Forty-six patients with biopsy-proven MGN were enrolled from April 2017 to June 2019 with 31/46 (67.4%) being primary and 15/46 (32.6%) being secondary as determined by comprehensive clinical assessment. This is currently deemed to be the gold standard for distinguishing primary from secondary MGN. Amongst the 31 primary MGN patients, 24/31 were positive on PLA2R DIF staining compared to 18/31 being positive on the PLA2R ELISA (p=0.03). Amongst the 15 secondary MGN patients, 1/15 was positive on PLA2R DIF compared to 0/15 on PLA2R ELISA (p=1.0). In conclusion, the presence of PLA2R staining on DIF demonstrated superior sensitivity and similar specificity compared to the detection of circulating PLA2R antibodies by ELISA in the diagnosis of primary MGN in a cohort of 46 patients with biopsy-proven MGN. We suggest that DIF should be considered as part of routine work-up in all newly diagnosed cases of MGN.

Phospholipase-A2 receptor antibody, 24hours proteinuria, and serum albumin as indicators of cyclophosphamide efficacy in idiopathic membranous nephropathy.

BackgroundWe aimed to evaluate cyclophosphamide efficacy in the treatment of idiopathic membranous nephropathy (IMN) and explore the efficacy of phospholipase‐A2 receptor antibody (PLA2R‐Ab), 24 hours proteinuria, and serum albumin in predicting 6‐ and 12‐month treatment effects.MethodsA retrospective analysis was performed on 135 patients with IMN who followed up after treatment. The observation points were before, and after 3, 6, and 12 months of treatment. We collected clinical indicator data at each observation point and measured PLA2R‐Ab levels before and after 3‐month treatment.ResultsThe remission rates at 3, 6, and 12 months of cyclophosphamide therapy for patients with IMN were 41.4, 74.8, and 76.1%, respectively. Patients in whom PLA2R‐Ab turned negative within 3 months had high remission rates at 3, 6, and 12 months after treatment (P < .05). PLA2R‐Ab change at 3 months had a strong correlation with 24 hours proteinuria change at 6 months. The change in albumin concentration before and after 3‐month treatment was an independent variable related to remission rate at 6 months, and 24 hours proteinuria change before and after 6‐month treatment was an independent variable related to remission rate at 12 months after treatment.ConclusionCyclophosphamide showed good efficacy at 3, 6, and 12 months for patients with IMN. Serum albumin change and PLA2R‐Ab change at 3 months can be used as indicators to predict remission at 6 months, respectively. Moreover, 24 hours proteinuria change at 6 months can predict remission at 12 months.

Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy.

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.

Rituximab in Patients With Phospholipase A2 Receptor–Associated Membranous Nephropathy and Severe CKD

IntroductionPatients with phospholipase A2 receptor (PLA2R)–associated membranous nephropathy and stage 4 or 5 chronic kidney disease are at high risk of end-stage kidney disease. In recent years, rituximab (RTX) emerged as a safe and efficient treatment for patients with PLA2R-associated membranous nephropathy. Whether its use is also appropriate in patients with an estimated glomerular filtration rate <30 ml/min per 1.73 m2 has not been investigated.MethodsWe retrospectively reviewed characteristics and outcome of 13 patients with PLA2R-associated membranous nephropathy and stage 4 or 5 chronic kidney disease who received a total of 14 consecutive RTX treatments from January 2012 to March 2018. The treatment regimen consisted of either 2 weekly infusions of 375 mg/m2 or 2 RTX infusions of 1 g/d two weeks apart. When needed, the regimen was repeated to achieve immunological remission.ResultsThe mean estimated glomerular filtration rate, serum albumin level, and urinary protein level at the first RTX infusion were 18 ± 7 ml/min per 1.73 m2, 25.2 ± 5.4 g/l, and 13.2 ± 7.5 g/d, respectively, with all patients being tested positive for serum PLA2R antibodies. Ten treatment courses led to an increase in estimated glomerular filtration rate and remission of nephrotic syndrome after a median follow-up of 40.8 months (interquartile range, 14.8–46.8). Conversely, 4 RTX treatments were unsuccessful, with patients requiring chronic hemodialysis within 1 year. The urinary albumin-to-protein ratio before treatment was predictive of renal response. Immunological remission occurred after 11 treatment courses and was associated with clinical response in 10 of 11 patients. Three patients experienced severe adverse events.ConclusionRTX seems effective and reasonably safe in PLA2R-associated membranous nephropathy with stage 4 or 5 chronic kidney disease. Immunological remission is associated with a good clinical outcome.

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

BackgroundIdiopathic membranous nephropathy (IMN) is widely considered as an organ-specific autoimmune disorder. Implicated in its pathogenesis are the phospholipase A2 receptors (PLA2R) expressed on glomerular podocytes against which serum antibodies are formed. In this study we quantified and assessed the clinical value of total serum PLA2R antibodies and the subtype antibodies in IMN. MethodsWe measured serum levels of total PLA2R antibodies and IgG subtype antibodies by Enzyme Linked Immunosorbent Assay (ELISA) in 146 biopsy-proven IMN patients, 51 non-IMN patients and 62 healthy controls. We went ahead and determined the diagnostic potential of total serum PLA2R antibodies and assessed if a relationship exists between the dominat subtype antibody and the clinical parameters. ResultsThe diagnostic sensitivity and specificity of total serum PLA2R antibody for IMN were found at 69.9% and 100% respectively. Significant differences in systolic blood pressure, serum Cystatin C, serum albumin and estimated glomerular filtration rate (eGFR) were found between the antibody-positive and antibody-negative groups of IMN patients. Subtype antibody 4 and 1 exhibited the highest positive rates of 94.4% and 91.6% respectively. The mean serum proportion of subtype antibodies was 65.4, 12.7, 7.6 and 4.6% for subtype 4, 1, 3 and 2 respectively. Serum levels of total protein and albumin were significantly decreased among patients with high serum titres of antibody subtype 4. ConclusionOur findings underscore the diagnostic potential of total serum PLA2R antibodies and highlight the importance of antibody subtype 4 over other subtype antibodies in IMN.