Cases Of Idiopathic Membranous Nephropathy Research Articles

Single-dose telitacicept therapy for refractory idiopathic membranous nephropathy: A case series.

We report three cases of IMN from our center, where patients received a single dose of telitacicept after showing no response to conventional treatments. Although one case did not respond, the other two cases achieved complete or partial remission of proteinuria. These cases illustrates the telitacicept may offer new hope for the treatment of IMN. Despite the variety of treatment options available, effective therapies for refractory membranous nephropathy remain lacking. Recently, some reports have suggested that telitacicept is a new therapeutic option. However, only a few published studies have documented the use of telitacicept for treating idiopathic membranous nephropathy (IMN). We present three cases of IMN from our center, where patients received a single dose of telitacicept after showing no response to conventional treatments, including glucocorticoids, tacrolimus, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab. Although one case did not respond, the other two cases achieved complete or partial remission of proteinuria. Thus, telitacicept may offer new hope for the treatment of refractory membranous nephropathy.

Deep analysis of total serum N-glycome suggests glyco-signatures for phospholipase A2 receptor 1-related idiopathic membranous nephropathy diagnosis

Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study. SignificancePLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.

Clinicopathological and prognostic characteristics of idiopathic membranous nephropathy with dual antigen positivity.

Idiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear. Immunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center. We identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients. For patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.

Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study

Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. A retrospective cohort study. We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.

Membranous nephropathy associated with immunoglobulin G4-related disease successfully treated with obinutuzumab.

ABSTRACTImmunoglobulin G4 (IgG4)-releated disease is typically associated with interstitial nephritis, but rare cases of idiopathic membranous nephropathy as a renal manifestation have been described. Obinutuzumab was successfully used in refractory membranous nephropathy, but evidence for the treatment of IgG4-related disease with obinutuzumab is lacking. We report one patient's case with membranous nephropathy associated with IgG4-related disease who was treated with obinutuzumab following an anaphylactic reaction to rituximab. Obinutuzumab treatment resulted in a sustained complete remission of membranous nephropathy and a decrease of IgG4 to the normal range. This case demonstrates that membranous nephropathy associated with IgG4-related disease can be treated successfully with obinutuzumab.

Immunosuppressive Treatments for Idiopathic Membranous Nephropathy: A Pilot Study According to Histopathological Stages

BackgroundNo scholar has explored whether immunosuppressive treatments at different histopathological stages are different for idiopathic membranous nephropathy (IMN). MethodsFrom January 1, 2012, to January 1, 2018, all biopsy confirmed IMN cases treated with glucocorticoid (GC) plus cyclophosphamide (CTX) or GC were retrieved from the patients’ medical records. ResultsThe present study included 67 patients who received GC alone (31 with stage I, 30 with stage II and 6 with stage III) and 157 patients who received GC + CTX (77 with stage I, 66 with stage II and 14 with stage III). Primary efficacy assessments included achieving complete remission and remission. Secondary efficacy assessments included proteinuria, serum albumin and adverse events. GC + CTX group showed higher complete remission rates than the GC group after 6 and 12 months in patients with stage II IMN (22% vs 10%, P = 0.04 and 59% vs 17%, P < 0.001, respectively). However, the two groups showed no difference in stages I and III (29% vs 26%, P = 0.61, 71% vs 52%, P = 0.09 and 14% vs 17%, P = 0.81, 21% vs 17%, P = 0.88, respectively). The GC + CTX group suffered a higher rate of gastrointestinal symptoms than the GC group in stage I and a higher rate of abnormal liver function in stage II. ConclusionsTreatment with GC + CTX was more effective than GC in treating patients with stage II IMN; however, the advantage of GC + CTX was not significant for patients with stage I and III IMN.

Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy

Idiopathic membranous nephropathy (IMN) as a single organ autoimmune disease is a main cause of nephrotic syndrome in adults which is determined through autoantibodies to podocytes proteins. Th17/regulatory T (Treg) balance has emerged as a prominent factor in the regulation of autoimmunity. In this study, we evaluated the balance of Th17 and Treg cells, expression level of related master transcription factors, cytokines and microRNAs in mononuclear cells of peripheral blood of 30 patients with IMN and 30 healthy individuals before treatment.No significant variation was observed in Th17 cell frequency, retinoic acid receptor‐related orphan nuclear receptor γt (RORɣt), signal transducer and Activator of transcription 3(STAT3), IL-17, and IL-23, while IL-21, IL-4, and IL-10 had significant increase in mRNA expression and protein level of peripheral blood mononuclear cells in IMN cases. Reduction in the percentage of Treg cells was also accompanied with significantly decreased expression of Forkhead box P3(FOXP3) and Transforming growth factor beta(TGF-β) in IMN patients compared to the control group.Our study revealed that Th17 cells themselves might not be engaged in the pathogenesis of newly diagnosed patients with IMN; however, decreased T reg cells and increased ratio of Th17/Treg lymphocytes might display a role in the pathogenesis of IMN before treatment.

The optimal anti-phospholipase A2 receptor cutoff for the diagnosis of idiopathic membranous nephropathy: a single-center retrospective study.

Background/AimsAnti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters.MethodsA total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency.ResultsThe optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate.ConclusionsThe recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

Differential analysis of urinary albumin for membranous nephropathy patients by online capillary isoelectric focusing - Mass spectrometry

Membranous nephropathy (MN) is one of the most common causes of primary glomerular diseases worldwide. The M-type phospholipase A2 receptor (PLA2R), an antigen expressed in more than 70% of cases of idiopathic membranous nephropathy (IMN), is a biomarker which is now used by physicians for clinical diagnosis. Despite the prevalence of PLA2R in the cases of MN, it is not always effective to use PLA2R for differentiating primary or secondary MNs. On the other hand, urinary albumin assay is one of the de facto tests for kidney function testing for several decades. In this work, urinary albumin species between primary and secondary MN patients are compared using a newly developed capillary isoelectric focusing – mass spectrometry (CIEF-MS) technology. The distinct patterns of cationic and acidic urinary albumin species, as revealed by this novel CIEF-MS technology, suggest potential applications of this differential analysis for subtyping of membranous nephropathy. Further investigation of these cationic human albumin species in urine may provide clues to the disease onset and development of MN, thus facilitating treatment. In addition, this novel workflow of using CIEF-MS for urinary protein analysis may be beneficial to the research, pathology, prognosis, and diagnosis of many other types of kidney diseases, such as chronic kidney disease, diabetic nephrology, etc.

PLA2R: The Same Target Antigen of Idiopathic Membranous Nephropathy and Hashimoto's Thyroiditis?

Background: Autoimmune thyroid disease associated nephropathy was identified 40 years ago; however, the cause of the disease remains unknown. Methods: Phospholipase A2 receptor (PLA2R) antibodies was assayed quantitatively in the serum of patients with Graves' disease, Hashimoto's thyroiditis (HT), idiopathic membranous nephropathy (IMN) and normal controls by time-resolved fluoroimmunoassay. PLA2R antigens were immunohistochemically analyzed in the thyroid tissue with Graves' disease and HT, as well as the nephridial tissue with IMN. Findings: The concentration of phospholipase A2 receptor (PLA2R) antibodies in the serum of normal controls, patients with Nodular goiter, Graves' disease and HT, as well as patients with IMN was 1.13 ± 0.43 mg/L, 1.07 ± 0.22mg/L, 2.12 ± 2.11mg/L, 8.07 ± 4.74mg/L, and 15.91 ± 19.50mg/L, respectively. The concentration of PLA2R antibodies in the serum and its areas under the curve of ROC in HT and IMN cases increased significantly. The immunohistochemistry revealed that the tissues of the patients with HT were obviously stained, with a positive rate of 66.67%. Interpretation: PLA2R may be a pathogenic target antigen for HT, and the production of anti-PLA2R antibodies may cause autoimmune thyroid disease associated nephropathy. Funding Statement: Clinical Medical Science fund of Jiangsu Province (No. BL2014022), Jiangsu Maternal and Child Health Research Project (FRC201741), and Wuxi City Science and Education Project (ZDRC006) supported the study. Declaration of Interests: All Authors declare no competing financial interests. Ethics Approval Statement: Patients from Jiangsu Jiangyuan Hospital and the Wuxi People’s Hospital affiliated to Nanjing Medical University, were enrolled. The study protocol was approved by the medical ethics committee of Jiangsu Jiangyuan Hospital and Affiliated Wuxi People's Hospital of Nanjing Medical University.

Membranous nephropathy and cancer in the era of PLA2R testing

Membranous nephropathy has historically been associated with a higher risk of malignancy compared to the general population. Following a membranous nephropathy diagnosis, physicians screen patients for underlying cancers at the time of and up to several years following the diagnosis. The discovery of phospholipase A2 receptor (PLA2R) as a major antigen in primary membranous nephropathy may be changing how we think about the association between membranous nephropathy and cancer. PLA2R was found to be present in 72% of cases of idiopathic membranous nephropathy with very few PLA2R patients having cancer. Following PLA2R discovery, thrombospondin type-1 domain-containing 7A (THSD7A) was discovered. This antigen, in contrast to PLA2R, may be more strongly associated with cancer. This review will evaluate the associations between these antigens and cancer, as well as propose an algorithm on cancer screening in the era of antibody testing.

Comparison of prognostic, clinical, and renal histopathological characteristics of overlapping idiopathic membranous nephropathy and IgA nephropathy versus idiopathic membranous nephropathy

Overlapping idiopathic membranous nephropathy (IMN) and immunoglobulin A nephropathy (IgAN) is rare. This study aims to investigate the unique prognostic, clinical, and renal histopathological characteristics of IMN+IgAN. This retrospective observational study included 73 consecutive cases of IMN+IgAN and 425 cases of IMN treated between September 2006 and November 2015. Prognostic and baseline clinical and histopathological data were compared between the two patient groups. Poor prognostic events included a permanent 50% reduction in eGFR, end-stage renal disease, and all-cause mortality. Renal histopathology demonstrated that the patients with IMN+IgAN presented with significantly increased mesangial cell proliferation and matrix expansion, increased inflammatory cell infiltration, and higher proportions of arteriole hyalinosis and lesions than the patients with IMN (all P < 0.05). Kaplan–Meier analysis showed that the patients with IMN+IgAN had significantly higher cumulative incidence rates of partial or complete remission (PR or CR, P = 0.0085). Multivariate Cox model analysis revealed that old age at biopsy and high baseline serum creatinine and uric acid levels were significantly associated with poor prognosis (all P < 0.05), and increased IgA expression correlated significantly with PR or CR (P < 0.05). The present study found that overlapping IMN and IgAN presents with unique renal histopathology and appears not to cause a poorer prognosis than IMN.

Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy

Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks. We identified significant entropy differences between MLN and IMN for all markers except C3 and IgG1, but mutual information (a measure of mutual dependence) were not significantly different for all the pairs of markers. The entropy differences between MLN and IMN, therefore, were not attributable to the mutual information. These findings suggest that disease type directly and/or indirectly influences the glomerular deposits of most of IgG subclasses and complements, and that the interactions between any pair of the markers were similar between the two diseases. A Markov chain of IgG subclasses was derived from the mutual information about each pair of IgG subclass. Finally we developed an integrated disease model, consistent with the previous findings, describing the glomerular immune deposits of the IgG subclasses and complements based on a Bayesian network using the Markov chain of IgG subclasses as seed. The relationships between the markers were effectively explored by information theory and Bayesian network. Although deposits of IgG subclasses and complements depended on both disease type and the other markers, the interaction between the markers appears conserved, independent from the disease type. The disease model provided an integrated and intuitive representation of the relationships of the IgG subclasses and complements in MLN and IMN.

Association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy.

This study was to investigate the relation between the number of autophagosomes in podocytes and the syndromes of idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (sMN). The pathological changes in the kidney tissues of patients were detected with the hematoxylin and eosin staining, the periodic acid-Schiff reagent treatment, the Masson's trichrome staining and the immunofluorescence detection (IF). Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the IF assay pointing to LC3-II, an autophagic marker. Clinical data, including age, sex, edema, serum creatinine, estimated glomerular filtration rate, hematuria, urine protein excretion and serum albumin, were collected from in-patient medical records. Finally, the association of podocyte autophagosome numbers with idiopathic membranous nephropathy and secondary membranous nephropathy was studied. Fewer autophagosomes were observed in podocytes of nephropathy group compared with the control group. Moreover, there was a significant difference in the autophagosome number between the two types of MN and each kind of nephropathy demonstrated distinct characteristics. Although the reduced autophagosome number in the IMN cases was not related to sex, this trend was exacerbated along with the progression from pathological stage I to II. In contrast, fewer autophagosomes were observed in class II and V LN patients compared with the controls, while greater numbers were detected in class III and IV LN patients. The results indicated that the autophagy participated in the podocyte injury in IMN and sMN and the number of autophagosomes in podocytes was related to the pathological classification.

How many podocyte autophagosomes are there in immunoglobulin A nephropathy and idiopathic membranous nephropathy?

The aim of this study was to investigate the number of autophagosomes in podocyte from kidney tissue of immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN). The changes in kidney tissue pathology were detected after hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome and immunofluorescence. The autophagosomes of podocyte were analyzed by transmission electron microscopy. Clinical data, including age, gender, edema, serum creatinine, estimated glomerular filtrating rate (eGFR), hematuria, urine protein excretion and serum albumin, were collected from inpatient medical record. It was found that the number of autophagosomes in podocyte of nephropathy group was lower when compared to the control group. At the same time, we did not find the difference of the parameter between these two kinds of nephropathy. Further study showed that the index was affected by two factors: eGFR and gender. The cases with worse eGFR (eGFR<60ml/min) and male patients presented more autophagosomes. Furthermore, each nephropathy had its own character. The phenomena of reduced autophagosomes were found in IMN cases, did not change from male to female, and further aggravated from pathological stage I to II. By contrast, IgAN cases with less eGFR exhibited more autophagosomes. Therefore, the results of the present study indicate that autophagy participates in podocyte injury and the progression of IgAN and IMN.

The Prognostic Significance of IgG4 Deposition in Membranous Nephropathy and Its Impact on the Therapeutic Regimen

Objectives: To assess the prognostic value of IgG4 reactivity in biopsy-proven cases of idiopathic membranous nephropathy (iMN) and to outline its potential in guiding therapy. Methods: A retrospective study of biopsy-proven iMN cases from January 1997 to August 2013 was undertaken. Patients were identified, and an extensive analysis of the clinical and histological parameters were performed. The primary endpoint was a worse renal outcome, which was defined as doubling of the serum creatinine baseline value. Results: The study included 52 patients, with mean age of 38.0 years. The median baseline creatinine was 112.7 ± 36.3 umol/l among those with positive staining for IgG4 and 67.4 ± 19.3 umol/l among those with negative staining for IgG4 (P=0.5). There was no significant difference in the 24 hr urine protein between IgG4 positive and IgG4 negative staining cases (P=0.375). The probability of doubling serum creatinine was similar among those with or without IgG4 deposition. Follow up of the patients revealed that 23.4% of those with positive IgG4 and 14% of those with negative IgG4 had deterioration of the renal function. The prevalence and severity of tubulo-interstitial inflammation was not statistically different between the two groups. Conclusion: There was no relationship between IgG4 positivity and the severity of clinical and/or histological parameters in patients with iMN. IgG4 reactivity had no impact on the long-term outcome of the patients. Further studies are needed to outline the potential use of targeted therapy against IgG4 auto-antibody in a certain category of patients with membranous nephropathy.

Application of Immunohistochemistry and Immunofluorescence Staining in Detection of Phospholipase A2 Receptor on Paraffin Section of Renal Biopsy Tissue

To evaluate the application of immunohistochemistry and fluorescence staining method in the detection of phospholipase A2 receptor (PLA2R) on paraffin section of renal biopsy tissue,and to find an accurate and fast method for the detection of PLA2R in renal tissue. The PLA2R of 193 cases were detected by immunohistochemical staining,and the antigen was repaired by the method of high pressure cooker (HPC) hot repair plus trypsin repair. The 193 samples including 139 cases of idiopathic membranous nephropathy (IMN), 15 cases of membranous lupus nephritis, 8 cases of hepatitis B virus associated membranous nephropathy, 18 cases of IgA nephropathy, and 13 cases of minimal change diseases. To compare the dyeing effects, 22 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 4 different. of antigen repairing,which included HPC hot repair, HPC hot repair plus trypsin repair, water bath heat repair, and water bath heat repair plus trypsin repair. To compare the dyeing effects, 15 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 3 different. of antigen repairing,which included water bath heat repair plus trypsin repair, protease K digestion repair, and pepsin digestion repair. In 193 cases, the positive rate of PLA2R in IMN cases was 90.6% (126/139), and the other 54 patients without IMN were negative. Twenty-two IMN patients were positive for PLA2R by using the HPC heat repair plus trypsin repaire or the water bath heat repair plus trypsin repair;while only a few cases of 22 IMN cases were positive by using the HPC hot repair alone or water bath heat repair alone. Fifteen IMN patients were positive for PLA2R by using water bath heat repair plus trypsin repair,protease K digestion repair,and pepsin digestion repair, but the distribution of positive deposits and the background were different. PLA2R immunohistochemical staining can effectively identify IMN and secondary MN. For immunohistochemical staining and immunofluorescence staining, the preferred method of antigen repair is water bath heat repair plus trypsin repair.

Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m-type phospholipase A2 receptor (PLA2R) are seen in two-thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti-PLA2R in paediatric IMN. We evaluated anti-PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti-PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN.

Bortezomib therapy for nephrotic syndrome due to idiopathic membranous nephropathy

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adults. The nephrotic syndrome due to idiopathic membranous nephropathy is often resistant to glucocorticosteroids and requires an alkylating agent such as chlorambucil or cyclophosphamide to induce remission. Recent studies illustrate that antibodies against the autoantigen M-type phospholipase A2 receptor contribute to a vast majority but not all cases of idiopathic membranous nephropathy. Herein, we report a patient with nephrotic syndrome due to membranous nephropathy that was resistant to 6months of therapy with ramipril and high-dose glucocorticosteroids but responded to a single cycle of bortezomib infusion.

Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy

Antibodies to the phospholipase A2 receptor 1 (PLA2R1) have been reported in 70% of cases of idiopathic membranous nephropathy (IMN). The genetic susceptibility of IMN has been accounted for by HLA DQA1 and PLA2R1 genes. Here we retrospectively quantified PLA2R antibodies by ELISA, and genotyped DQ alleles and PLA2R1 single-nucleotide polymorphisms for association with clinical criteria for disease activity at the time of first sample and with outcome over a median total follow-up of 90 months. In 90 prevalent patients with biopsy-proven IMN, anti-PLA2R antibodies were present in 75% of patients with IMN with active disease and were significantly higher than in patients in partial or complete remission at the time of antibody measurement. There was a differential IgG subclass response (4>2>3>1) at an early stage, i.e., within 6 months of biopsy. Levels of PLA2R antibodies were significantly linked to DQA1*05:01 and DQB1*02:01. Survival analysis of patients with IMN showed that PLA2R antibodies are significantly linked with outcome. Thus, high levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up. Future therapeutic trials in IMN should monitor anti-PLA2R, as patients with a high antibody burden may benefit from earlier therapeutic intervention.