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Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.
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Objective:To analyze the clinicopathological characteristics, treatment responses and kidney outcomes of patients with atypical membranous nephropathy (MN), and to provide information for the clinical practice.Methods:The clinical data of patients with atypical MN and synchronous primary MN who were diagnosed, treated and followed up in Peking University First Hospital from January 2008 to June 2020 were retrospectively collected and analyzed. Clinicopathological features, treatment responses and kidney prognosis were compared between the two groups. The expression of phospholipase A2 receptor (PLA2R) in kidney tissues was detected by immunofluorescence. Serum anti-PLA2R antibody was detected by enzyme-linked immunosorbent assay. Clinicopathological indexes were compared between PLA2R-related MN group and non-PLA2R-related MN group. Kaplan-Meier (Log-rank test) survival curve and multivariate Cox regression analysis methods were used to analyze the influencing factors of kidney prognosis in patients with atypical MN. The primary endpoint of renal adverse outcome was renal insufficiency, defined as end-stage renal disease or estimated glomerular filtration rate (eGFR) decline>30% baseline and<60 ml·min -1·(1.73 m 2) -1. Results:A total of 65 atypical MN patients were enrolled in this study. Compared with primary MN ( n=324), patients with atypical MN had younger age ( Z=-4.229, P<0.001), higher proportion of hematuria ( χ2=5.555, P=0.018), higher level of urinary protein ( Z=2.228, P=0.026) and lower level of eGFR ( t=-5.108, P<0.001); the proportion of IgG4 deposition in kidneys was lower ( χ2=8.081, P=0.004), and the proportions of IgA ( χ2=16.969, P<0.001) and IgM ( χ2=9.281, P=0.002) deposition were higher. There was no significant difference on gender, serum albumin, positive proportion of anti-PLA2R antibody, anti-PLA2R antibody level and kidney C3/C1q deposition between the two groups (all P>0.05). The proportions of atypical MN patients receiving renin-angiotensin aldosterone system inhibitors (49.3% vs 57.1%), calcineurin inhibitors (27.7% vs 19.1%) and cyclophosphamide (21.5% vs 23.8%) were comparable to those of primary MN patients (all P>0.05). The rates of clinical remission (80.0% vs 77.2%), partial remission (44.6% vs 44.1%), complete remission (35.4% vs 33.1%), spontaneous remission (36.9% vs 42.6%), response to cyclophosphamide (85.7% vs 81.8%), response to calcineurin inhibitor (88.9% vs 79.0%), and relapse (30.8% vs 26.8%) in atypical MN patients were comparable to those in primary MN patients (all P>0.05). During the follow-up 30.0(21.5, 61.5) months, 15 atypical MN patients (23.1%) had eGFR reduction>30%, among whom 7 patients (10.8%) had eGFR reduction>50% and 3 patients (4.6%) had end-stage kidney disease. There was no significant difference on poor kidney prognosis between the two groups (all P>0.05). Kaplan-Meier survival curve showed that patients with age>39 years old ( χ2=10.092, P=0.001), eGFR≤100 ml·min -1·(1.73 m 2) -1( χ2=5.491, P=0.019), tubular interstitial lesion ( χ2=6.999, P=0.008) and no nephropathy remission ( χ2=22.952, P<0.001) had earlier poor renal prognosis. Multivariate Cox regression analysis showed that no nephropathy remission ( HR=12.604, 95% CI 2.691-59.037, P=0.001) was an independent influencing factor for poor renal prognosis in atypical MN patients. Conclusion:No significant difference is found between atypical MN and primary MN on treatment responses and kidney prognosis, which implies that clinical practice of atypical MN can be performed by referring to the guidelines and experience of primary MN.
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Objective:To investigate the correlation between serum anti phospholipase A2 receptor (PLA 2R) antibody level and the condition and prognosis of patients with primary membranous nephropathy (PMN).Methods:61 patients who were diagnosed as PMN in the laboratory department of Jiangsu Province Hospital of Chinese Medicine from January 2017 to August 2019 were selected and divided into PLA 2R positive group (41 cases) and PLA 2R negative group (20 cases) according to the level of PLA 2R antibody. The gender, age and other general data of the two groups were collected, and the clinical pathological characteristics and prognosis of the two groups were analyzed. Spearman correlation was used to analyze the correlation between the level of PLA 2R antibody and the disease condition and treatment prognosis.Results:The levels of estimate glomerular filtration rate (eGFR), total protein (TP) and albumin (ALB) in PLA 2R positive group were lower than those in PLA 2R negative group, while the levels of 24-h urinary protein and IgG4 were higher in PLA 2R positive group than that in PLA 2R negative group ( P<0.05); Multivariate logistic regression analysis showed that 24-hour urinary protein was an independent risk factor for PLA 2R antibody level ( OR=2.242, P<0.05), while TP and ALB levels were protective factors ( OR=0.840, 0.674, P<0.05); The patients in both groups were followed up for one year by rechecking serological indexes. The complete remission rate and total remission rate of PLA 2R positive group were lower than those of PLA 2R negative group ( P<0.05); Spearman correlation analysis showed that the level of PLA 2R antibody was negatively correlated with the levels of TP, ALB, and prognosis of patients ( r=-0.642, -0.547, -0.357, P<0.05), and positively correlated with the level of 24-hour urinary protein ( r=0.347, P<0.05). PLA 2R in renal tissue of 61 patients was found to be positive in 63.93% (39/61). Conclusions:The level of PLA 2R antibody is closely related to serum albumin, TP, 24 h urinary protein and prognosis of patients with PMN.
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Background: The discovery of the phospholipase A2 receptor antigen and its highly specific autoantibody (anti-PLA2R Ab) was useful for the diagnosis and follow-up of patients with membranous nephropathy (MN). Thus, some international guidelines recommend not performing renal biopsy in patients with positive serum anti-PLA2R Ab. Aim: To evaluate the prevalence of anti-PLA2R Ab in serum and renal tissue samples from Chilean patients with primary MN. Material and Methods: Twenty-eight patients aged 50 ± 14 years (20 males) with biopsy-proven primary MN plus a negative workup for secondary causes were included. Measurements of serum and renal histologic anti-PLA2R Ab were performed. The relationship between the findings of serum and tissue anti-PLA2R Ab was evaluated. Results: Fifteen patients (54 %) had anti-PLA2R Ab presence in serum and 19 patients (68%) had positive anti-PLA2R Ab in the renal biopsy. All patients with positive serum anti-PLA2R Ab had positive antibodies on immunohistochemistry. Conclusions: Serum anti-PLA2R Ab is potentially useful in the diagnosis of patients with suspected primary MN in Chilean population.
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ABSTRACT Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.
RESUMO A Nefropatia Membranosa Idiopática (NMi) é uma frequente causa de síndrome nefrótica em adultos e sua etiologia pode ser estratificada em primária/idiopática ou secundária. O conhecimento da fisiopatologia da NMi sugeriu a presença de autoanticorpos (PLA2R e a THSD7A) direcionados contra antígenos existentes nos podócitos. A detecção de anticorpos contra um domínio favorece NMi. A presença de autoanticorpos contra um desses domínios autoexcluiria a possibilidade de autoanticorpos contra o outro domínio; no entanto, recentemente foram descritos casos que apresentaram dupla positividade para PLA2R e THSD7A, comprovando que, por mecanismos fisiopatológicos ainda não conhecidos, raramente pode existir produção concomitante de anticorpos contra os dois alvos. O presente estudo tem por objetivo relatar o caso de um paciente de 46 anos de idade, do sexo masculino, que apresentou quadro de proteinúria nefrótica, hematúria, hipoalbuminemia e hipercolesterolemia submetido a biópsia e exame histopatológico (ML, IF, IHQ e ME), confirmando um caso raro de NMi com positividade dupla para os anticorpos anti-PLA2R e anti-THSD7A e associação à nefropatia por IgA, mostrando nossa experiência com a utilização de subclasses de IgG, PLA2R e THSD7A na rotina laboratorial para a investigação da GNM e enfatizando a importância de uma abordagem ampla para adequada elucidação e conhecimento dos mecanismos fisiopatológicos na NMi.
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Humans , Male , Middle Aged , Glomerulonephritis, Membranous/immunology , Thrombospondins/immunology , Receptors, Phospholipase A2/immunology , Biopsy , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/etiology , Glomerulonephritis, Membranous/pathology , Kidney Glomerulus/pathologySubject(s)
Glomerulonephritis, Membranous , Epitopes , Humans , Receptors, Phospholipase A2 , RituximabABSTRACT
BACKGROUND: Serum anti-phospholipase A2 receptor (PLA2R) antibody was correlated with disease activity of membranous nephropathy(MN). The predictive value of antibody titer changes on immunosuppressive response remains unknown. We investigated predictive value of dynamic change of anti-PLA2R antibody and 24-h urine protein (24hUP) for clinical response of MN. METHODS: This was a retrospective cohort study including 47 Chinese MN patients with positive anti-PLA2R antibody in a tertiary referral hospital between January 2012 and March 2014. Patients received cyclophosphamide (CTX, n = 23), or cyclosporine (CYA, n = 24) regimen, respectively. We monitored serum anti-PLA2R titer and 24hUP at one, three and six-month follow-up. RESULTS: At baseline, total patients were 42 ± 14 years old with 29/18 male/female ratio. The median 24hUP was 5.80(3.56,9.41) g/d. The median baseline anti-PLA2R antibody titer was 66.4(31.9, 188.0) RU/mL. Baseline 24hUP and eGFR between subgroups were not significantly different. The differences of relative reduction between antibody titer and 24hUP at one month were statistically significant (CTX group 94.2% vs. 46.8%, P < 0.001; CYA group 54.6% vs. 4.6%, P = 0.04). Only in CTX group, the relative reduction of 24hUP at one month was correlated with composite remission at six-month(P = 0.03). Area under the curve of 24hUP relative reduction in CTX group at one-month for predicting composite remission at six months was 0.85(95%CI 0.65~1.05, P = 0.04). The cutoff value of one-month's 24hUP relative reduction for predicting six-month's composite remission in CTX group was 15.3%, with high sensitivity (83.3%) and specificity (100%). CONCLUSIONS: Compared with relative reduction of antibody titer, relative reduction of 24hUP at one-month follow-up in CTX group had a better predictive value for six-month's composite remission.
Subject(s)
Autoantibodies/blood , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/drug therapy , Immunosuppressive Agents/therapeutic use , Receptors, Phospholipase A2/immunology , Adult , Area Under Curve , Female , Glomerular Filtration Rate , Glomerulonephritis, Membranous/complications , Humans , Male , Middle Aged , Proteinuria/etiology , Proteinuria/urine , ROC Curve , Retrospective StudiesABSTRACT
Objective To assess the efficacy and safety of tacrolimus combined with prednisone for treat-ment of refractory idiopathic membranous nephropathy(IMN)patients whose serum anti-phospholipase A2receptor (PLA2R)antibody titers were persistent high. Methods An open prospective study of 12 refractory IMN patients was performed in Guangzhou First People's Hospital between June of 2012 and June 2016.The 12 patients failed to re-spond after a standard course of 6 months in a conventional immunosuppressive therapy(cyclophosphamide,myco-phenolate mofetil or cyclosporine A)combined with prednisone and the patients'serum anti-PLA2R antibody titers were persistent high. They were divided into two groups:The tacrolimus group received tacrolimus combined with prednisone for 12 months and the control group received the same or another conventional immunosuppressive therapy for 6 months.Results At the end of the sixth month after enrollment,proteinuria and serum albumin levels in the ta-crolimus group were significantly improved as compared with those in the control group(P<0.01),and eGFR was higher in the tacrolimus group than in the control group(P<0.05).Severe proteinuria and hypoalbuminemia still re-mained in the control group,and eGFR in the control group declined significantly prior to enrollment(P<0.01).Af-ter 6-month treatment,none of the control group became negative for serum anti-PLA2R antibody,and achieved clini-cal remission. Five patients(83.3%)in the tacrolimus group became negative for serum anti-PLA2R antibody and achieved clinical remission(complete remission in two patients and partial remission in three).After 12-month treat-ment,complete remission was achieved in four patients(66.7%)in the tacrolimus group.Conclusions Persistent high serum anti-PLA2R antibody titers may be a cause of no response to a conventional immunosuppressive therapy in refractory IMN patients.For these patients,tacrolimus combined with prednisone may be an effective alternative treat-ment for disappearance of anti-PLA2R antibody and remission.
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Objective To identify the significance of serum phospholipase A2 receptor antibody (PLA2R-Ab) in idiopathic membranous nephropathy (IMN) patients.Methods A total of 108 patients diagnosed as IMN by medical history,physical examination,laboratory examination and renal biopsy in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Dec 1,2014 and Aug 31,2017 were enrolled,and all related data were recorded.According to the results of serum PLA2R-Ab test,patients were divided to positive group and negative group,and the data were compared with the independent sample t test and the chi-square test.Kaplan-Meier survival analysis was performed to compare remission rates between groups,and the Logrank method was used to evaluate the significance of differences.Univariate and multivariate Cox regression analysis were used to verify predicting factors for achieving remission.Results Overall,67.6％(73/108) patients had detectable serum PLA2R-Ab.Compared with patients in negative group,patients in positive group exhibited higher proportion of male patients (P=0.002),lower level of serum albumin (P ＜ 0.001),higher level of cholesterol (P ＜ 0.001),lower level of immunoglobulin G (P ＜0.001),higher level of proteinuria (P=0.003),a lower of chance of remission (P=0.049),longer time needed to achieve partial remission (P=0.001) and complete remission (P=0.002).The 1-and 2-year cumulative renal partial remission rates were 72.4％,86.1％,and the cumulative renal complete remission rates were 43.8％,54.0％,respectively.Patients in negative group had higher partial remission (x2=9.84,P=0.002) and complete remission (x2=15.50,P＜0.001) than those in positive group.Multivariate Cox regression model indicated that serum positive PLA2R-Ab was a significant independent risk factor.Conclusions IMN patients with serum PLA2R-Ab show more severe condition and lower remission rates than those without serum PLA2R-Ab.Serum positive PLA2R-Ab is an independent remission-related predictor for IMN patients.
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Objective To explore the relationship of phospholipase A2 receptor (PLA2R) expression in renal tissue with clinical characteristics,prognosis of idiopathic membranous nephropathy (IMN) patients.Methods 134 patients diagnosed as nephropathy proven by biopsy was selected as subjects of this research,including 98 patients with IMN patients,10 patients with secondary membranous nephropathy and 26 patients with other renal glomerular diseases.The expression of PLA2R antigen in renal tissue was detected by immuno-fluorescence chemistry staining.Results The positive rate of renal PLA2R expression in IMN patients was higher than that in SMN patients (91.84％ vs 40.00％,P＜ 0.01),whereas there is no expression in other glomerular diseases.The PLA2R negative group were mainly stage Ⅰ membranous nephropathy,and positive group was mainly in stage Ⅱ.The distribution of pathological stage between the two groups was statistically significant (P ＜0.01).Compared with the positive group,the negative group was manifested with higher eGFR[(115.91± 23.32) ml· min-1 · (1.73 m2)-1 vs (94.06±27.38) ml· min-1 · (1.73 m2)-1,P=0.031],associated with the higher 12-month complete remission rate (87.50％ vs 44.07％,P=0.021).Conclusions The expression of PLA2R antigen in renal tissue plays an important role in the diagnosis,disease evaluation and prognosis of IMN.The negative PLA2R in kidney tissue of IMN may indicate a good clinical prognosis.
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Objective To investigate the clinico-pathological features of idiopathic membranous nephropathy (IMN ) and the expression of phospholipase A2 receptor (PLA2R ) in elderly patients. Methods A total of 109 elderly patients with IMN confirmed by renal biopsy at Wuxi People's Hospital from July 2008 to February 2015 were included.Data were retrospectively collected. Results (1)Participating patients with IMN had a mean age of (67.3 ± 5.4)years ,and 67.9% of them had hypertension and 65.1% had nephrotic syndrome.Compared with non-elderly patients ,elderly patients had a higher proportion with hypertension (67.9% vs.25.2%)(P＝0.000) ,higher systolic pressure[(143.1 ± 15.2)mmHg vs. (127.3 ± 13.3)mmHg](P＝ 0.000) ,higher diastolic pressure [(88.4 ± 10.0)mmHg vs. (80.2 ± 8.4)mmHg](P＝ 0.000) ,more severe tubulointerstitial lesions [(3.1±1.9)points vs.(2.0±1.9)points](P＝0.000),and lower eGFR[(70.9±22.9)ml·min－1· 1.73 m －2vs. (90.6 ± 27.1 ) ml·min－1·1.73 m －2] ( P ＝ 0.000 ). (2 ) There were more severe tubulointerstitial lesions[(4.7 ± 1.8)points vs. (2.4 ± 1.7)points ,2.9 ± 1.6 points](P ＝ 0.000 , 0.000)and lower eGFR[(50.4 ± 17.4)ml·min－1·1.73 m －2vs. (80.3 ± 19.7)ml·min－1·1.73 m －2, (72.3 ± 21.4)ml·min－1·1.73 m －2](P＝0.000 ,0.000)in elderly patients of pathological stage Ⅱ, compared with patients of pathological stages Ⅰ and Ⅰ-Ⅱ. (3)The rate of positive PLA2R was 82.4%.Patients with positive PLA2R had higher proteinuria[(4.5 ± 2.3)g vs. (2.9 ± 1.1)g](P＝0.042) ,lower eGFR[(66.8 ± 21.8)ml·min－1·1.73 m －2vs. (97.7 ± 16.0)ml·min－1·1.73 m －2](P＝0.000) ,and more severe tubulointerstitial lesions [(3.1 ± 2.0)points vs. (1.7 ± 1.1)points](P＝0.037)than patients with negative PLA2R. (4)Multiple regression analysis showed that PLA2R positive rate(P＝0.008) ,tubulointerstitial lesion(P＝0.000) ,and level of cholesterol(P＝0.025)were negatively correlated with eGFR (R2＝0.572). Conclusions Compared with non-elderly patients , elderly patients with IMN have poorer prognosis as a result of higher blood pressure and more severe tubulointerstitial lesions.Elderly patients with IMN of advanced pathological stages and positive PLA2R have more severe kidney injury and tubulointerstitial lesions ,resulting in poor prognosis.
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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 MannWhitney 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 (x2 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 AntiPLA2R-TRFIA has been well established.This quick and easy-performance method could increase the diagnostic accuracy for IMN.
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BACKGROUND AND OBJECTIVES: Thrombospondin type-I domain-containing 7A (THSD7A) was recently identified as the target antigen in about 10% of patients with M-type phospholipase A2 receptor (PLA2R)-negative membranous nephropathy in European and North American populations. The prevalence of THSD7A in other populations and their clinical associations deserve further clarification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Immunofluorescence assay was performed to investigate anti-THSD7A antibodies in 578 consecutive patients with biopsy-proven idiopathic membranous nephropathy, 114 patients with secondary membranous nephropathy, 64 disease controls, and 20 healthy controls. Glomerular expression of THSD7A antigen was examined by immunohistochemistry. Anti-PLA2R antibodies and glomerular PLA2R expression were also screened. RESULTS: Among the 578 patients with idiopathic membranous nephropathy, 12 (2%) patients were identified as THSD7A-positive: ten patients were THSD7A-positive alone, which accounted for 16% (ten of 64) of PLA2R-negative patients; two patients were dual-positive for both anti-THSD7A and anti-PLA2R antibodies and showed enhanced expression of both antigens colocalized in glomeruli. Among the 114 patients with secondary membranous nephropathy, one among 44 (2%) patients with cancer had anti-THSD7A antibodies, whereas 18 of 44 (41%) had anti-PLA2R antibodies. No anti-THSD7A antibody was detected in other disease controls or healthy individuals. Clinical features were comparable between the patients with and without THSD7A. During follow-up, two patients who achieved remission had a clearance of circulating antibodies against THSD7A, whereas antibodies increased in parallel with proteinuria in a patient with a relapse. CONCLUSIONS: THSD7A-associated membranous nephropathy has a low prevalence in Chinese patients. The double-positive patients suggest dual autoimmune responses.
Subject(s)
Autoantibodies/blood , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/immunology , Kidney Glomerulus/immunology , Thrombospondins/immunology , Adult , Aged , Asian People , Biopsy , China/epidemiology , Female , Fluorescent Antibody Technique , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/ethnology , Humans , Kidney Glomerulus/pathology , Male , Middle Aged , Prevalence , Receptors, Phospholipase A2/immunology , Retrospective Studies , Young AdultABSTRACT
In recent years, the diagnosis of idiopathic membranous nephropathy (IMN) has been more and more important with the rapid growth rate on incidence in China.Previous diagnosis of IMN depends on renal biopsy, a gold standard, but a high risk of traumatic examination.The detection of serum PLA2R antibody and THSD7A antibody to assist in the diagnosis of is not only fast, sensitive, simple and noninvasive, but also can reflect the immune status in real time.Compared with the traditional proteinuria severity based therapeutic efficacy evaluation, that is more effective and agile to monitor the disease condition, reflect the treatment effects and predict the prognosis better.Therefore, it should be vigorously promoted.
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Over the past decade , with the rapid increase of the incidence of idiopathic membranous nephropathy (IMN) in our country, the diagnosis and treatment of IMN has been paid more and more attention.IMN is an autoimmune disease.Two important podocyte autoantigens , PLA2R and THSD7A, have been indentified sine 2009.Subsequently , serum anti-PLA2R antibody test and anti-THSD7A antibody test have also been used in clinical .Preliminary applications show that these two tests can not only help IMN diagnosis and differential diagnosis , but also help IMN prognosis.
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Objective To detect the M-type phospholipase A2 receptor (PLA2R),and thrombospondin type-1 domain-containing 7A (THSD7A) expression in renal tissue and the levels of their antibodies in adult idiopathic membranous nephropathy (IMN).Also to determine the value of the two markers in the diagnosis of IMN.Methods One hundred and sixteen patients with biopsyproven MN at the Second Hospital of Hebei Medical University from December 2014 to August 2015 were enrolled,including 86 patients with IMN,10 patients with HBV-MN and 10 patients with stage Ⅴ lupus nephritis (LN-Ⅴ).Twenty patients with minimal change disease (MCD) were regarded as control group.We conducted immunohistochemical analysis of the presence of THSD7A and PLA2R the Paraffin section and enzyme linked immunosorbent assay (ELISA) detecting serum PLA2R-AB and THSD7A-AB concentration to investigate whether there was a correlation between them and clinical indicators.Results Compared with the SMN and MCD groups,the positive rates of PLA2R and PLA2R-AB were significantly higher in IMN groups.Expression PLA2R was detected in 88.4％,47.4％,10％ and 0％ and PLA2R-AB in 82.6％,15％,10％,0％,respectively,of the patients with IMN,HBV-MN,LN-Ⅴ and MCD.Expression THSD7A was detected in 2.3％ of the patients with IMN while not detected in SMN and MCD.THSD7A-AB antibody was negative in all patients.Compared with serum PLA2R-Ab negative individuals,patients with serum PLA2R-Ab positive had lower serum albumin (P ＜ 0.001),higher urine protein excretion (P=0.01).The sensitivity of PLA2R-AB,PLA2R,THSD7A and PLA2R+THSD7A in the diagnosis of IMN were 82.6％,88.4％,2.3％,88.6％,and the specificity was 92％,66.7％,100％,66.7％,respectively.Conclusions PLA2R in renal tissue and serum PLA2R-AB are specific markers for the diagnosis of IMN,which are closely related with the severity of IMN.Expression of THSD7A is only positive in some of IMN patients with negative PLA2R,which can be used as a supplementary examination of IMN patients with negative PLA2R.
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Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis,differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients.Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled,consisting of 90 IMN,20 secondary membranous nephropathy (SMN),82 IgA nephropathy (IgAN),30 minimal changed disease (MCD),16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN).Their clinical data including age,sex,serum creatinine (Scr),serum albumin and 24 h urinary protein were collected.Serum PLA2R1 was measured by enzyme linked immunosorbent assay.PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay.The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed.Results Compared with IMN patients,SMN,MCD and FSGS patients were younger (all P ＜ 0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P ＜ 0.001); MPGN patients had higher Scr (all P ＜ 0.01).The positive rate of serum PLA2R1 was 75.6％ in IMN patients,while it was 0.0％ in non-IMN patients.The distribution between serum PLA2R1 and pathological diagnosis had difference (P ＜ 0.001),their positive coincidence rate was 100％,negative coincidence rate was 87.4％,total coincidence rate was 90.9％ and their consistency was well (Kappa=0.795,P ＜ 0.001).Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli,only moderate or more positive IgG4 had statistical differences (82.2％ vs 5.0％,P ＜ 0.001); the positive rate of glomerular PLA2R1 was 41.1％ in IMN patients,higher than 10.0％ in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0％ vs 0.0％,P ＜ 0.001),which could improve the diagnostic specificity of IMN.In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P＜0.001).Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315,P=0.002),negatively correlated with serum albumin (r=-0.228,P=0.030) and didn't correlate with Scr (r=0.199,P=0.059).Conclusions Serum PLA2R can be used as the specific indicator for diagnosis,differential diagnosis of IMN and to reflect the severity of IMN in patients.
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Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years,to investigate diagnostic and differential diagnostic value of serum antiphospholipase A2 receptor antibodies (PLA2R-Ab),and to evaluate the correlation between PLA2R-Ab and clinical disease activity.Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients,including 1567 IMN cases,admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved.Demographics and pathological type were gathered from all patients.(2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved,with their clinical and laboratorial data being collected.During the period patients' follow-up time,therapeutic schedule and laboratory results were recorded.Results (1) IMN accounted for 22.4％ of primary glomerular disease,and patients above 40 years old accounted for more than 60％ of the IMN.(2) The sensitivity and specificity of serological PLA2R-Ab were 58.1％(95％CI 47.0％-68.5％) and 98.6％(95％CI 95.6％-99.6％) respectively.PLA2R-Ab positive rate was affected by immunosuppression therapy.(3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017,P=0.887),serum albumin (r=-0.072,P=0.549) and urinary red blood cell count (r=-0.030,P=0.802).There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage Ⅰ-Ⅱ (P ＞ 0.05).Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant.After (2.21± 1.09) months,the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P ＜ 0.05).Condusions The incidence of IMN increase year by year,especially in the mid-aged and the elderly.Serum PLA2R-Ab correlates not with IMN pathological stage,but with the development of IMN.Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.
ABSTRACT
Chagas disease (CD) - a tropical parasitic disease caused by the protozoan Trypanosoma cruzi - is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure.
ABSTRACT
Objective To investigate the diagnostic value and monitoring application of anti-phospholipase A2 receptor antibodies ( PLA2R ) in patients with idiopathic membranous nephropathy ( IMN) .Methods A retrospective study was used .48 patients were diagnosed as idiopathic membranous nephropathy by puncturing kidney from January of 2013 to June of 2014 in the Hospital of Liaoning Traditional Chinese Medical University and Shengjing Hospital of China Medical University were included. 43 patients were diagnosed as non-idiopathic membranous nephropathy ( NIMN ).35 healthy volunteers were selected as control groups.Serum PLA2R were detected by indirect immunofluorescence.The intensity of antibodies fluorescence and the level of urine protein in 24 hours(24 h PRO) ,serum UREA ,serum CYSC, serum UA,GFR were compared in each groups.Measurement data was shown as mean ±standard deviation;Count data was shown as frequency or composition, t test andχ2 test were used as statistical method.Results (1) Among 48 cases with IMN,37 cases showed positive PLA2R (positive rate 77.08%).All of cases were negative in NIMN group.The sensitivity and the specificity of serum PLA2R were 77.08%and 100%.(2) Compared with control groups, the levels of UREA, CYSC and UA were found statistically significant differences in patients with IMN ( P 0.05 ) . ( 3 ) Positive correlation were found between 24 h PRO(r=0.877,P=0.00),serum UA (r=0.766,P=0.00 ) with the level of PLA2R antibodies fluorescence intensity.( 4 ) There were no correlation between serum PLA2R antibody with IMN pathology aging (r=0.087,0.194,0.182;P=0.598,0.399,0.667).PLA2R positive rate(Ⅰstage:37.50%,Ⅱstage:84.85%, Ⅲstage 85.71%) may increases with the increasing of illness severity.Conclusion Serum PLA2R antibody would be a new laboratory diagnosis standard in patients with IMN.(Chin J Lab Med, 2015, 38:595-599 ) Objective To investigate the diagnostic value and monitoring application of anti-phospholipase A2 receptor antibodies ( PLA2R ) in patients with idiopathic membranous nephropathy ( IMN) .Methods A retrospective study was used .48 patients were diagnosed as idiopathic membranous nephropathy by puncturing kidney from January of 2013 to June of 2014 in the Hospital of Liaoning Traditional Chinese Medical University and Shengjing Hospital of China Medical University were included. 43 patients were diagnosed as non-idiopathic membranous nephropathy ( NIMN ).35 healthy volunteers were selected as control groups.Serum PLA2R were detected by indirect immunofluorescence.The intensity of antibodies fluorescence and the level of urine protein in 24 hours(24 h PRO) ,serum UREA ,serum CYSC, serum UA,GFR were compared in each groups.Measurement data was shown as mean ±standard deviation;Count data was shown as frequency or composition, t test andχ2 test were used as statistical method.Results (1) Among 48 cases with IMN,37 cases showed positive PLA2R (positive rate 77.08%).All of cases were negative in NIMN group.The sensitivity and the specificity of serum PLA2R were 77.08%and 100%.(2) Compared with control groups, the levels of UREA, CYSC and UA were found statistically significant differences in patients with IMN ( P 0.05 ) . ( 3 ) Positive correlation were found between 24 h PRO(r=0.877,P=0.00),serum UA (r=0.766,P=0.00 ) with the level of PLA2R antibodies fluorescence intensity.( 4 ) There were no correlation between serum PLA2R antibody with IMN pathology aging (r=0.087,0.194,0.182;P=0.598,0.399,0.667).PLA2R positive rate(Ⅰstage:37.50%,Ⅱstage:84.85%, Ⅲstage 85.71%) may increases with the increasing of illness severity.Conclusion Serum PLA2R antibody would be a new laboratory diagnosis standard in patients with IMN.
