Serum Phospholipase A2 Receptor Antibody Research Articles

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.

Dual-antigen sandwich-type time-resolved fluoroimmunoassay for phospholipase A2 receptor antibody, a new marker of membranous nephropathy

Objective To establish a time-resolved fluoroimmunoassay (TRFIA) method for detecting M-type phospholipase A2 receptor (PLA2R) antibody and to investigate the diagnostic value of serum PLA2R antibody for idiopathic membranous nephropathy (IMN). Methods The microplates coated with recombined PLA2R antigen and Eu3+ -streptavidin labeled PLA2R antigen were used to establish a dual-antigen sandwich-type TRFIA for PLA2R antibody detection (anti-PLA2R-TRFIA). The serum concentrations of PLA2R antibody in 63 IMN patients (36 males, 27 females, age 25-75 years) and 90 healthy volunteers (30 males, 60 females, age 22-53 years) were quantitatively analyzed. Kruskal-Wallis H test and Mann-Whitney u test were used to analyze the data. Results The range of anti-PLA2R-TRFIA was 0-10 mg/L and the sensitivity was 5 μg/L, while ED20, ED50 and ED80 of the standard curve were (0.144±0.012), (0.707±0.029) and (3.466±0.098) mg/L, respectively. The CV of inter- and intra-assay were 4.7% and 5.1%, respectively. The average concentration of serum PLA2R antibody in healthy volunteers was 0.455(0.320, 0.593) mg/L, but in IMN patients it was 2.690(0.717, 7.750) mg/L (z=-3.688, P<0.05). Meanwhile, the serum levels of PLA2R antibody in IMN patients were significantly different between different stages and ages (χ2 values: 10.328, 9.716, both P<0.05). According to the receiver operating characteristic (ROC) curve, when the diagnostic cut-off was set at 0.80 mg/L for IMN detection, the sensitivity and specificity of anti-PLA2R-TRFIA were 73.0%(46/63) and 95.6%(86/90), respectively. Conclusions Anti-PLA2R-TRFIA has been well established. This quick and easy-performance method could increase the diagnostic accuracy for IMN. Key words: Glomerulonephritis, membranous; Receptors, phospholipase A2; Fluoroimmunoassay

Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy.

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb- (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb-/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.

Clinicopathological characteristics of M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy in Japanese

Recent studies have suggested that assessments of serum antibodies against M-type phospholipase A2 receptor (PLA2R) and the glomerular expression of PLA2R antigen in biopsy specimens are useful for the diagnosis of primary membranous nephropathy (MN). In this study, we assessed both of them and investigated the clinicopathological characteristics of PLA2R-related Japanese MN. We retrospectively enrolled 22 primary and 3 secondary Japanese patients whose serum samples and renal specimens were collected before treatment. According to the findings of serum antibodies and antigen in glomeruli, the primary MN patients were classified into PLA2R-related or -unrelated MN. We compared their clinicopathological findings, including IgG subclass staining, and electron microscopic findings, and evaluated the predictors of proteinuria remission. In primary MN, 16 patients (73 %) were classified into the PLA2R-related group, and 6 patients into the PLA2R-unrelated group. There was no significant difference in baseline laboratory data and electron microscopic findings, except for eGFR and serum IgG levels. IgG4-dominant deposition was more common in the related group (63 vs. 0 %). The 10 PLA2R-related patients with dominant IgG4 deposition had a lower rate and prolonged time in remission compared with the 6 PLA2R-related patients with non-dominant IgG4 (log-rank, p = 0.032). Furthermore, dominant IgG4 deposition was an unfavorable predictor of remission by multivariable Cox proportional hazard analysis. Assessments of both serum PLA2R antibodies and PLA2R antigen in glomeruli were more sensitive for the diagnosis of PLA2R-related MN, and among affected Japanese patients, those with dominant IgG4 deposition had worse clinical outcomes.

Phospholipase A2 Receptor Autoantibodies and Clinical Outcome in Patients with Primary Membranous Nephropathy

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A2 receptor (PLA2R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA2R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA2R antibodies who had not received immunosuppressive therapy. Patients were followed ≤24 months. PLA2R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA2R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA2R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA2R antibody levels achieved remission of proteinuria significantly later than patients with low PLA2R antibody levels. PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA2R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary MN.