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Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.
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Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.
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Humans , Autoantibodies , Clinical Relevance , Colonic Neoplasms , EGF Family of Proteins , Glomerulonephritis, Membranous/diagnosis , Nephrotic Syndrome , Receptors, Phospholipase A2/metabolism , Thrombospondins/metabolismABSTRACT
Objective:To compare the clinicopathological differences between elderly and non-elderly patients with idiopathic membranous nephropathy(IMN).Methods:Patients diagnosed with IMN via renal biopsy at Beijing Huairou Hospital, Beijing Changping Hospital of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine from January 2017 to August 2021 were retrospectively enrolled.They were classified into the elderly group(≥65 years)and the non-elderly group(<65 years), and the clinicopathological differences between the two groups were compared.Results:A total of 207 IMN patients were included in the study, with a male to female ratio of 1.7∶1.0.There were 56 patients in the elderly group, aged(68.2±3.1)years, and 151 patients in the non-elderly group, aged(48.2±6.2)years.Compared with the non-elderly group, the elderly group had a longer time from onset to renal biopsy and a higher proportion of patients with renal insufficiency and hypertension( P<0.05). The elderly group had a lower eGFR, lower serum albumin, higher serum cholesterol, and higher low-density lipoprotein than the non-elderly group( P<0.05). The proportions of patients with glomerulosclerosis, renal tubular atrophy, and interstitial fibrosis in the elderly group were higher than in the non-elderly group( P<0.05). The positive rates of glomerular PLA2R antigen staining in the two groups were 90.6%(29/32)and 91.0%(111/122), respectively, and there was no statistically significant difference between the two groups.IgG4 deposition represented the most common IgG subtype, with 93.8%(30/32)in the elderly group and 94.3%(115/122)in the non-elderly group.There was no statistical significance between the two groups( P>0.05). Conclusions:Compared with non-elderly IMN patients, a higher proportion of elderly IMN patients has renal insufficiency, hypertension and chronic renal pathology.The glomerular deposition of pathogenic antigens in elderly IMN patients was similar to that in non-elderly IMN patients, suggesting no difference in pathogenesis between the two groups.The clinicopathological differences between the two groups may be related to age and complications.
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Objective:To evaluate the curative effect of Moshen Decoction combined with routine western medicine on idiopathic membranous nephropathy (IMN) of spleen-kidney qi deficiency syndrome and explore its influences on renal function, C1q, PLA2R and E-cadherin levels.Methods:A total of 62 patients with IMN meeting inclusion criteria in the hospital were enrolled between January 2018 and January 2021. According to simple random grouping method, they were divided into control group (hormones combined with cyclophosphamide) and observation group (Moshen Decoction on basis of control group), 31 in each group. Both groups were treated continuously for 6 months. Before and after treatment, TCM syndromes were scored. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), cystatin C (Cys-C), anti-phospholipase A2 receptor (PLA2R) and E-cadherin (EC) were detected by ELISA. The level of serum complement C1q was detected by immunoturbidimetry. The 24 h urine was collected for quantitative determination by full-automatic biochemical analyzer. The adverse events during treatment were observed and recorded. And clinical curative effect was evaluated.Results:The differences in total response rate between observation group and control group were statistically significant [93.55% (29/31) vs. 74.19% (23/31); χ2=4.29, P=0.038]. After treatment, scores of TCM syndromes (edema of lower limbs, fatigue and poor appetite, lusterless complexion) in observation group were significantly lower than those in the control group ( t=10.07, 10.80, 4.34, 4.57, P<0.001). After treatment, levels of serum Cys-C [(0.51±0.05) mg/L vs. (0.55±0.06) mg/L, t=2.85], 24 h urine protein quantification [(0.95±0.19) g vs. (1.38±0.23) g, t=13.32] in observation group were lower than those in the control group ( P<0.01), and levels of serum PLA2R [(17.53±1.84) Ru/ml vs. (19.62±2.05) Ru/ml, t=4.22], EC [(2.74±0.26) μg/L vs. (3.05±0.37) μg/L, t=3.82] and complement C1q [(152.34±15.62) mg/L vs. (169.33±16.77) mg/L, t=4.13] in observation group were significantly lower than those in the control group ( P<0.01). During treatment, there was no significant difference in incidence of adverse events between observation group and control group [12.90% (4/31) vs. 16.13% (5/31); χ2=0.13, P=0.781]. Conclusion:Moshen Decoction combined with routine western medicine can improve renal function and clinical curative effect in patients with IMN of spleen-kidney qi deficiency syndrome. Its mechanism of action may be related to reducing urine protein, complement C1q, PLA2R and EC.
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A 43-year-old male patient with onset of edema caused by nephrotic proteinuria and low titer of anti-M type phospholipase-A 2-receptor (PLA 2R) antibody was diagnosed as idiopathic membranous nephropathy by renal biopsy. Administrated with prednisone 40 mg once a day and cyclosporine 100 mg twice a day as front-line regimen, the patient relapsed after transient partial remission. When treatment was combined with cyclophosphamide 100 mg once a day, the 24-hour total urine protein and titer of anti-PLA 2R antibody were even elevated. Therefore, the patient received rituximab 1 g intravenously in April 2019, October 2019 and October 2020 respectively. CD19 positive B lymphocytes in peripheral blood were eliminated from 71/μl to zero. Immunosuppressants and corticosteroids were withdrawn successively. On the last follow-up in November 2020, the anti-PLA 2R antibody was negative, and the 24-hour total urine protein and serum albumin was 4.4 g and 34 g/L, respectively. This case suggested the potential efficacy of rituximab for refractory membranous nephropathy. Further studies should explore whether the titer of anti-PLA 2R antibody indicates the dose of rituximab.
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Objective:To analyze the clinical and prognosis of primary membranous nephropathy (PMN) in children with positive glomerular M-type phospholipase A2 receptor (PLA2R).Methods:A total of 69 children diagnosed with PMN by renal biopsy admitted to the Department of Pediatrics of Eastern Theater Command General Hospital from January 2006 to December 2018 were retrospectively analyzed, including 40 males and 29 females, with an average age of 14.86 years.According to the immunofluorescence of renal pathology, they were divided into PLA2R positive group and PLA2R negative group.Pathological features between 2 groups were compared by the t test, Mann- Whitney U test and Chi- square test.Kaplan-Meier method was used to compare the long-term renal survival rate and cumulative remission rate between 2 groups. Results:A total of 69 pediatric PMN patients were included.The po-sitive rates of serum anti-PLA2R antibody and positive expression of PLA2R in renal tissues were 53.6% (37 cases) and 82.6% (57 cases), respectively.The proportion of children with clinical manifestations of large proteinuria [55 cases(96.5% ) vs.9 cases(75.0%), P=0.034] was significantly higher in the PLA2R positive group than that of the PLA2R negative group.Blood urea nitrogen level was significantly higher in the PLA2R positive group than that of PLA2R negative group[1.14(0.93, 1.54) mg/L vs.0.80 (0.44, 1.18) mg/L, P=0.049], while estimate glomerular filtration rate(eGFR) [162.26 (139.81, 185.53) mL/(min·1.73 m 2) vs.199.52 (157.58, 212.01) mL/(min·1.73 m 2), P=0.034] and serum IgG [3.58 (2.50, 5.43) g/L vs.5.14 (4.35, 6.03) g/L, P=0.016] were significantly lower.The cumulative remission rate was significantly higher in the PLA2R negative group than that of PLA2R positive group ( P<0.001). The 24 h urinary protein ≥50 mg/kg ( HR=0.119, 95% CI: 0.021-0.595, P=0.010)was an independent risk factor for renal prognosis, and PLA2R( HR=0.263, 95% CI: 0.125-0.551, P<0.001) and 24 h urinary protein ≥50 mg/kg ( HR=0.568, 95% CI: 0.125-0.551, P=0.041)were independent predictors of urinary protein remission.PLA2R ( HR=1.020, 95% CI: 0.698-1.682, P=0.656)was not associated with renal prognosis. Conclusions:The severity of PMN in children with positive PLA2R was higher than that in those with negative PLA2R.The long-term cumulative remission rate of PLA2R negative children with PMN was higher than that of PLA2R positive children.
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Objective@#To analyze the distribution of glomerular immunofluorescence IgG4 subtypes in primary membranous nephropathy, and to explore the relationship between IgG4 deposit intensity and renal pathology, clinical manifestations and prognosis.@*Methods@#All the patients of biopsy-proven primary membranous nephropathy with IgG staining and at least one IgG subtype staining 1+ or higher on capillary loops from September 2015 to April 2017 were retrospectively enrolled. The distribution of IgG4 deposits were analyzed, and the relationship between IgG4 positive intensity and clinical manifestations, pathological indexes and clinical remission was investigated.@*Results@#A total of 250 cases were enrolled, including 157 males (62.8%) and 93 females (37.2%), and age was (54.4 ± 14.6) years. There were 40 patients in IgG4-negative group, and 210 patients in IgG4-positive group. The IgG4-positive group was divided into subgroups as 114 cases of the mild positive subgroup (1+) and 62 cases of the moderate positive subgroup (2+), and 34 cases of the strong positive subgroup (3+, 4+). The IgG4-positive group had higher 24-hour urine protein and higher positive rate of phospholipase A2 receptor staining than those in the negative group (both P<0.05), while the strong positive subgroup had lower serum albumin and higher IgG1 staining than those in the mild positive subgroup (both P<0.05). There was no difference in the ratio of glomerular sclerosis, tubular atrophy, IgG2, IgG3 or other immunofluorescence between the groups. After a median follow-up of 180(122, 209) days, 32 individuals were lost to follow-up. Among the rest 218 patients, 45 patients (20.6%) got complete remission, 104 patients (47.7%) got partial remission, and 69 patients (31.7%) showed no response. For no response as the outcome event, multivariate Cox regression analysis showed that higher IgG4 staining intensity (HR=1.371, 95%CI 1.068-1.759, P=0.013), male (HR=1.818, 95%CI 1.028-3.214, P=0.040), higher 24-hour urine protein level (HR=1.108, 95%CI 1.003-1.225, P=0.043) were independent risk factors for disease remission.@*Conclusions@#The glomerular IgG4 positivity and intensity are related to the severity of primary membranous nephropathy. The glomerular IgG4 deposit degree may be an effective prognostic marker for the treatment response of primary membranous nephropathy.
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OBJECTIVES@#To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis.@*METHODS@#Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.@*RESULTS@#The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group.@*CONCLUSIONS@#PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.
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Humans , Autoantibodies , Glomerulonephritis, Membranous , Immunohistochemistry , Receptors, Phospholipase A2 , ThrombospondinsABSTRACT
OBJECTIVE: To investigate the clinicopathological features of phospholipase A2 receptor(PLA2R) negative patents with idiopathic membranous nephropathy(IMN). METHODS: IMN patients diagnosed by renal biopsy were enrolled in this study. Glomerular PLA2 R deposition(GAg) and serum anti-PLA2 R antibodies(SAbs) were detected by immunohistochemical staining and enzyme linked immunosorbent assay, respectively. Patients were divided into two groups. Both GAg and SAbs were negative in patients of Group A. Patients of group B were selected from patients who were positive for GAg and SAbs and were matched with group A in gender and age. The clinical and laboratory data of the two groups were collected. Glomerular thrombospondin type-1 domaincontaining 7A(THSD7A) deposition and serum anti-THSD7 A antibody were also measured by immunohistochemical staining and indirect immunofluorescence in the two groups, respectively. RESULTS:(1) Compared with group B, patients in group A had lower levels of proteinuria, lower proportion of microscopic hematuria, higher remission rate(P<0.05). The positive rate of IgG4 in group A(45.0%) was significantly lower than that in group B(85.0%)(P<0.01).(2) The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody of group A were 17.5% and 7.5%. Patients in group B showed negative THSD7 A tissue staining and antiTHSD7 A antibodies. CONCLUSION: Compared with patients who were positive for GAg and SAbs, patients who were negative for GAg and SAbs exhibited lower levels of proteinuria and higher remission rate. The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody was low in patients with IMN.
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To develop and evaluate an ELISA kit for Anti-PLA2R IgG. Recombinant M-type phospholipase A2 receptor (PLA2R) protein expressed in HEK293 was taken as coating antigen, HRP-labeled rabbit anti-human IgG was taken as a tracer, to test the anti-PLA2R IgG on the basis of the principle of ELISA. The detection linear range, accuracy, linear correlation, repeatability, and stability were evaluated. In addition, we made a comparison with enrolled anti-PLA2R IgG kit. The detection linear range of the kit is no more than 2 RU/mL. The relative deviation of the kit accuracy is in -15%-15%. There is a linear correlation coefficient of higher than 0.990 0 within 2-500 RU/mL range. The CV of the repeatable test is lower than 15% when the kit was put in 37 ℃ one week, 2-8 ℃ one year, the performance remains. The consistency of testing with comparison in enrolled anti-PLA2R IgG kit is 98.9% (positive: 97.2%, negative: 100%). The Anti-PLA2R IgG ELISA Kit which we developed is nearly identical to the reference standard in specific and sensitive of clinics. It's successfully used to determine anti-PLA2R titer and help clinical diagnosis.
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Idiopathic membranous nephropathy(IMN) is one of the main pathology of nephrotic syndrome,and has a rising trend year by year.In recent years that IMN is organ specific autoimmune disease.Phospholipase A2 receptor(PLA2R) and thrombospondin type-1 domain containing 7A(THSD7A) are the two main antigens of IMN,which could be used to distinguish the IMN and secondary membranous nephropathy.The anti-PLA2R antibody and anti-THSD7A antibody are associated with diagnosis,severity and activity of the disease.The antibody titer and its change could be used to help deciding the beginning of therapy and the therapitive courses.
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After the research of PLA2R1 and its antibodies, Thrombospondin type-1 domain-containing 7A and its antibodies to membranous nephropathy (MN) has made a new understanding.Some researches have reported that the antibodies of PLA2R1 and THSD7A were mutually exclusive in MN, because THSD7A was found in PLA2R1-negative MN patients.But the latest researcher showed that these antibodies can be both positive in MN patients.Similar to the function of PLA2R1, THSD7A can assist clinical diagnosis, treatment, and monitor of MN.In contrast to PLA2R1, THSD7A was also highly expressed on both human and murine podocytes.We can use the mice model to study the pathogenesis of THSD7A-associated MN in the future.In this review, we describe the structure and function of Thrombospondin type-1 domain-containing 7A and its autoantibodies, highlight its role in MN and suggest possible aspects of its future clinical application.
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Objective To assess the efficacy of mycophenolate mofetil (MMF) combined with prednisone in the treatment of idiopathic membranous nephropathy (IMN) patients with positive serum phospholipase A2 receptor (PLA2R) antibody.Methods An open prospective study was performed on twenty-four biopsy-proven IMN patients with positive serum PLA2R antibody in Guangzhou First People''s Hospital from June 2012 to June 2016.The 24 patients were divided into two groups: MMF group in which MMF combined with prednisone was given for 12 months and CTX group in which intravenous cyclophosphamide (CTX) was monthly given combined with oral prednisone.Results After 6 months of immunosuppressive therapy,complete remission and partial remission rates were 25.0% vs.16.7% and 25.0% vs.25.0% in the MMF group and CTX group,respectively (P>0.05).In the MMF group and CTX group,serum PLA2R antibody in the same amount (8/12,66.7%) of patients turned negative.At the end of twelve-month treatment,all patients with negative PLA2R antibodies achieved complete or partial remission.Clinical remission (including complete and partial remission) rates in the MMF group and CTX group were both 66.7%.After immunosuppressive therapy,the levels of proteinuria and serum albumin in the two groups were significantly improved,but no significant difference were found between the two groups (proteinuria:F within-grouP=98.688,P<0.01;F between-grouP=0.133,P=0.719;F cross-grouP=1.223,P=0.304;serum albumin:F within-grouP=30.629,P<0.01;F between-grouP=0.137,P=0.715;F cros-grouP=0.455,P=0.565).At the end of six and twelve months of treatment,the proteinuria (after six months,MMF group: (2 893±2 515) mg/g vs.(6 236±2 117) mg/g,t=-3.522,P=0.002;CTX group: (2 690±2 254) mg/g vs.(5 386±2 447) mg/g,t=-2.808,P=0.010;after twelve months,MMF group:1 025(99-4 635) mg/g vs.(6 236±2 117) mg/g,Z=-3.291,P<0.0005;CTX group: (775(41-3 517) mg/g vs.(5 386±2 447) mg/g,Z=-3.118,P=0.001) and serum albumin levels (after six months,MMF group: (28.5±9.7) g/L vs.(19.8±4.4) g/L,t=2.841,P=0.012;CTX group: (29.0±7.6) g/L vs.(22.3±4.1) g/L,t=2.690,P=0.016;at the end of twelve months of treatment,,MMF group: (32.4±8.5) g/L vs.(19.8±4.4) g/L,t=4.570,P<0.0005;TX group: (32.2±7.9) g/L vs.(22.3±4.1) g/L,t=3.862,P=0.001) of the two groups were better than those prior to treatment.Conclusion For the IMN patients with positive serum PLA2R antibody,MMF combined with prednisone was as effective as conventional CTX combined with prednisone in the negative conversion of PLA2R antibody and the remission.The negative conversion of PLA2R antibody after 6 months of immunosuppressive treatment was an important indicator of predicting the remission.
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In recent years,the phospholipase A2 receptor in membranous nephropathy as an antigen has been confirmed,people have a new understanding of the mechanism of membranous nephropathy.Abundant clinical trials showed anti-PLA2R antibody in membranous nephropathy formed the important pathogenic mechanism,and it's related to disease activity,result and prognosis,it can also predict the process of disease remission,even can help make treatments for patients.This paper gathered some progress locally and abroad to describe the anti-PLA2R antibody's in function membranous nephropathy.
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Objective:To examine the expression ofphospholipase A2 receptor (PLA2R) in renal tissues and the level of anti-PLA2R antibody in serum in patients with idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (SMN),and to evaluate their diagnostic value in IMN.Methods:A total of 73 patients,who were diagnosed between May,2014 and February,2015 in the Department of Nephrology of the Second Xiangya Hospital,Central South University,were divided into three groups:an IMN group (n=48),an SMN group (n=17) and a minimal change disease group (n=8) according to the renal biopsy.PLA2R expression in renal tissues and the level of antiPLA2R antibody in serum were detected by indirect immunofluorescence technique.Results:The positive rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group were higher than those in the SMN group (91.7％ in the IMN group vs 29.4％ in the SMN group,P＜0.05),while the positive rate and serum level for anti-PLA2R antibody in the IMN group were higher than those in the SMN group (85.4％ in the IMN group vs 29.4％ in the SMN group,P＜0.05);the expression of PLA2R in renal tissues and the serum level for anti-PLA2R antibody were not detected in the minimal change disease group,The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (r=0.432,P＜0.01) and negatively correlated with serum albumin (r=-0.307,P＜0.05).Conclusion:The expression of PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be potential markers for diagnosis oflMN.
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Objective To investigate the features and correlation analysis of clinico-pathological and expression of phospholipase A2 receptor(PLA2R)in idiopathic membranous nephropathy. Methods A number of 244 patients of IMN proved by renal biopsy were recruited in Wuxi People's Hospital from July 2008 to February 2015. Data were restrospectively collected. Results In the 244 IMN patients(mean age 54.07 ± 15.22 years,130 males and 114 females),44.3% had hypertension and 62.7% had nephrotic syndrome. Compared with female patients ,male patients had more severe proteinuria and lower eGFR(P 8 g/24 h had higher level of cholesterol and blood pressure ,lower eGFR and more severe tubulointerstitial lesions(P < 0.05). Pathological stage Ⅰ and Ⅱaccounted for 98%,and there were more severe tubulointerstitial lesions and lower eGFR in the patients of stage Ⅱthan that in the patients of stageⅠandⅠ~Ⅱ(P<0.05). The positive rate of PLA2R accounted for 84.3%. Lower eGFR and more severe tubulointerstitial lesions were found in PLA2R-positive patients than those in PLA2R-neg-ative patients(P < 0.05). Multiple regression analysis showed that tubulointerstitial lesions(B =-7.253),hyper-tension ratio(B=-10.726)and the level of cholesterol(B=-2.077)had negative correlations with eGFR(P<0.01, R2=0.470). Conclusions IMN patients of male gender,grave proteinuria,high pathological stage and positive PLA2R should be treated more actively , since severe tubulointerstitial lesions and kidney injury were more common in those patients.
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Objective:To compare the difference of serum levels of M-phospholipaseA2 receptor ( PLA2R) antibodies in patients with idiopathic membranous nephropathy(IMN) detected by two different methods and evaluate the diagnostic value of two methods. Methods:Patients diagnosed as membranous nephropathy and other diseases with biopsy-proven from december 2014 to october 2015 in Shengjing Hospital of China Medical University were enrolled and devided into IMN group and non-IMN group. The serum levels of anti-PLA2R antibody were detected by both indirect immunofluorescence assay(IFA) and enzyme linked immunosorbent assay(ELISA). Results:The sensitivity of IFA and ELISA in IMN were 71. 3% and 68. 5%,and the specificities of two methods were the same as 100%. The area under ROC curves of anti-PLA2R antibody for IMN diagnosis were 0. 860 and 0. 839. The diagnostic value of IFA and ELISA was no statistically significant differences in IMN ( P>0. 05 ) , and the consistency of two methods was better (κ=0. 876). The IMN patients of positive anti-PLA2R antibody be susceptible to the low level of serum albumin (P<0. 05). The higher levels of PLA2R antibody were linked with the worse hypoproteinemia and the higher rate of nephrotic-range proteinuria in IMN patients. Conclusion:Two methods of detecting sera PLA2R antibody have higher sensitivity and specificity,so the sera anti-PLA2R antibody was a better biomarker in the diagnosis of idiopathic membranous nephropathy.
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Objective To detect the expression levels of renal tissue M-type phospholipase A2 receptor 1(PLA2R1) antigen and its antibody in the patients with membranous nephropathy(MN).Methods Fifty-eight cases of biopsy-proved idiopathic membranous nephropathy(IMN),fifteen cases of hepatitis B-associated membranous nephropathy(HBV-MN) and seventeen cases of V type lupus nephritis(V-LN) were selected.Renal tissue PLA2R1 antigen was detected by indirect immunofluorescence and colocaliazed with IgG4.Serum anti-PLA2R1 antibody was simultaneously examined.The expression difference of PLA2R1 antigen and antiPLA2R1 antibody in MN was analyzed.And the differences of clinical data were analyzed between PLA2R1 positive and negative patients.Results The PLA2R1 antibody was not found in the renal tissue and serum of the patients with LN and HBV-MN;PLA2R1 antigen was found in 81.03％ of IMN patients,and its antibody was found in serum of 70.69％ of IMN patients.PLA2R1 antigen and IgG4 co-localization all deposited along glomerular capillary loop presenting as fine granules.The 24 h urine protein level in the patients with PLA2R1 antigen deposition in renal tissues was higher than that in the patients without PLA2R1 deposition (P＜0.05),moreover serum albumin level was lower than that in the patients without PLA2R1 deposition(P＜0.05).Conclusion The sensitivity and specificity of renal tissue PLA2R1 antigen in the diagnosis of IMN are higher.The expression of PLA2R1 antigen in renal tissue by biopsy is significantly correlated with the clinical severity.
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Objective To analyze the expression of serum anti M phospholipase A2 receptor (PLA2R)antibody in idiopathic membranous nephropathy (IMN),and to investigate its value in the diagnosis and evaluation of idiopathic membranous ne-phropathy.Methods One hundred and eighteen patients with biopsy-proved glomerular diseases were involved in this study, including 97 cases with IMN,21 cases with IgA nephropathy (IgAN)and 19 healthy people.ELISA was used to detect ser-um anti-PLA2R antibodies.Correlations of anti-PLA2R antibody level with laboratory parameters,including serum albumin, 24-hour urine protein of IMN patients were evaluated.Results The median of anti PLA2R antibody in IMN group,IgAN group and healthy group was 45.2(3.6~705.9)RU/ml,5.9(2.3~10.6)RU/ml and 1.2(0.6~9.3)RU/ml.The levels of serum anti PLA2R antibody in IMN group were higher than those in IgA nephropathy group and healthy control group.The difference was statistically significant (t=-5.027,-3.077;P=0.05).Among 97 cases with IMN,76 cases showed posi-tive anti-PLA2R antibodies (positive rate 78.35%).There was none patient showed positive anti-PLA2R antibody respec-tively in IgAN and healthy people.Furthermore,anti-PLA2R antibody level was negatively correlated with serum albumin (r=-0.453,P=0.000)and positively correlated with CREA,TC,ESR,24 hour urine protein (r=0.233,0.234,0.363, 0.586;P=0.004,0.217,0.021,0.000)in IMN patients.Conclusion Serum anti PLA2R antibody may be used as a IMN specific marker for the diagnosis of IMN,and it has important reference value for evaluating the severity of IMN.
ABSTRACT
Objective To investigate the different expressions of plasma M type phospholipase A2 receptor antibody and IgG subtypes deposition of kidney tissues in idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropa-thy,and to evaluate the significance of plasma M type phospholipase A2 receptor antibody and IgG subtypes in diagnosis of hepatitis B virus-associated membranous nephropathy.Methods Plasma samples were obtained from patients with idiopathic membranous nephropathy,hepatitis B virus-associated membranous nephropathy and minimal change disease,respectively,before immunosup-pressive therapy.Concentration of plasma M type phospholipase A2 receptor antibody was detected by sandwich ELISA and concen-tration of IgG subtypes were measured by immunofluorescence.Results Concentration of plasma M type phospholipase A2 receptor antibody was (15.4±7.2)μg/mL in idiopathic membranous nephropathy group,higher than that in the hepatitis B virus-associated membranous nephropathy group (10.3±5.7)μg/mL (P <0.01),between idiopathic membranous nephropathy group and hepatitis B virus-associated membranous nephropathy group.There was no distinct difference of IgG subtypes deposition in glomerlar capil-lary wall.Conclusion There is obvious clinical significance of concentration of plasma M type phospholipase A2 receptor antibody in differential diagnosis of idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropathy,while no distinct significance of IgG subtypes deposition.