成人膜性肾病患者血清抗PLA2R抗体与病情的相关性

目的 分析成人膜性肾病患者血清抗M型磷脂酶A2受体(PLA2R)抗体与特发性膜性肾病( IMN)实验室指标的相关性,探讨抗PLA2R抗体在IMN发病中的作用.方法 选取经肾活检证实的46例肾小球疾病患者,包括20例IMN、7例IgA肾病、6例乙型肝炎病毒相关性膜性肾病( HBV-MN)、6例微小病变性肾病、4例局灶性节段性肾小球硬化、3例Ⅴ型狼疮肾炎.应用Western印迹法检测血清抗PLA2R抗体,并对其与IMN患者血清白蛋白、24 h尿蛋白量、血清总胆固醇和Scr作相关性分析.结果 20例IMN患者中15例血清抗PLA2R抗体阳性,阳性比例为75％;7例IgA肾病患者中1例抗PLA2R抗体阳性,阳性比例为14.29％;6例HBV-MN患者中1例阳性,阳性比例为16.67％;其余患者均为阴性.IMN患者血清抗PLA2R抗体阳性比例显著高于继发性膜性肾病和其他肾小球肾炎(均P＜0.01),且抗PLA2R抗体水平与IMN患者尿蛋白量呈正相关(r=0.803,P＜0.01);与血清白蛋白呈负相关(r=-0.816,P＜0.01).结论 IMN患者血清抗PLA2R抗体阳性比例高,提示抗PLA2R抗体可能是IMN的特异性抗体.该抗体与尿蛋白量呈正相关,提示抗PLA2R抗体可能是IMN的致病性抗体.     

Clinical significance of phospholipase A2 receptor 1 in patients with idiopathic membranous nephropathy

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.     

Expression and significance of M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in adult idiopathic membranous nephropathy

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 biopsy-proven 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.     

The significance of serum phospholipase A2 receptor antibody in remission of idiopathic membranous nephropathy

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 Log-rank 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(χ2=9.84, P=0.002) and complete remission (χ2=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.     

The clinical outcome and risk factors of phospholipase A2 receptor-associated idiopathic membranous nephropathy in adults

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults, as well as to explore the potential prognostic factors. Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected. Results PLA2R-associated IMN patients accounted for 89.2% of the IMN patients. Spontaneous remission occurred in 35.5% of PLA2R-associated IMN patients. The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P＜0.05). Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060, 95%CI 0.007-0.493, P=0.009), while higher serum albumin at baseline (OR=1.480, 95%CI 1.144-1.932, P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040, 95%CI 1.322-3.151, P=0.001) were independent protective factors for spontaneous remission. About 42.1% PLA2R-associated IMN patients had received immunosuppressive therapy, with induced remission rate being 70.7%. High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268, 95%CI 1.014-1.585, P=0.038). Conclusions PLA2R-associated IMN accounts for most of the IMN patients, with a spontaneous remission rate of 35.5%, during the follow-up period, which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer. Induced remission rate is 70.7% in patients in need of immunosuppresants. The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.     

Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies

1. Download high-res image (355KB)
2. Download full-size image

     

Prevalence of idiopathic membranous nephropathy and clinicopathologic correlation with serum anti-PLA2R antibody in a single center

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 anti-phospholipase 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). Conclusions 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.     

Relationship between renal phospholipase A2 receptor expression and clinical characteristics,prognosis in idiopathic membranous nephropathy patients

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.     

Podocyte expression of human phospholipase A2 receptor 1 causes immune-mediated membranous nephropathy in mice

1. Download : Download high-res image (340KB)
2. Download : Download full-size image

     

M型磷脂酶A2受体与膜性肾病的临床诊治:进展与争议

血清抗M型磷脂酶A2受体(phospholipase A2 receptor,PLA2R)抗体对特发性膜性肾病的诊断敏感性为70％～80％,特异性高达95％以上.本综述主要从PLA2R入手,阐述其在膜性肾病的发病机制、诊断、治疗、预后方面的进展,并探讨目前仍存在的一些争议:如何判定血清抗PLA2R抗体阳性以及其阳性能否...     

Mapping the T cell epitopes of the M-type transmembrane phospholipase A2 receptor in primary membranous nephropathy

1. Download : Download high-res image (284KB)
2. Download : Download full-size image

     

血清磷脂酶A2受体抗体预测利妥昔单抗治疗特发性膜性肾病疗效价值的初探

目的 探索血清磷脂酶A2受体抗体预测利妥昔单抗治疗特发性膜性肾病疗效的预测价值.方法 纳入2017年8月1日至2020年5月31日新疆维吾尔自治区人民医院首次确诊或长期随访使用利妥昔单抗治疗的特发性膜性肾病的患者120例,依据血清磷脂酶A2受体抗体情况将患者分为阳性组和阴性组,进行组间资料比较,用Kaplan-Meie...     

血清抗核抗体阳性的不典型膜性肾病与狼疮膜性肾病及特发性膜性肾病的临床病理比较

目的 探讨血清抗核抗体（ANA）阳性的不典型膜性肾病（AMN）与狼疮膜性肾病（LMN）、特发性膜性肾病（IMN）的关系，寻找对诊断LMN具有较高预测价值的临床和病理学指标。 方法 2003年1月至2006年12月期间在北京协和医院住院并行肾活检，临床、病理资料保存完整的患者为对象。分组：AMN组（n = 28）：血清ANA滴度≥1∶80，少于4条美国风湿病学会（ARA）修订的系统性红斑狼疮分类标准，病理呈肾小球基底膜病变伴系膜增生和（或）免疫荧光C1q阳性；IMN组（n = 100）；LMN组（n = 45）。回顾性分析各组病例的临床表现、病理学特点。应用免疫组化法，对各组部分病例肾活检组织行IgG亚型染色，半定量分析染色强度。对各组部分病例肾活检组织行免疫荧光双染色（IgG-TRITC，C3-FITC），用激光扫描共聚焦显微镜观察肾小球沉积的IgG和C3的空间分布。 结果 (1)AMN组起病年龄（38±17）岁，女∶男比为2.5∶1，介于LMN和IMN之间。3组起病年龄差异有统计学意义（P < 0.01），AMN组女∶男比高于IMN组（P = 0.017）。AMN组血液系统异常、血抗SSA抗体阳性百分比较高（21.4%、40.7%）。(2)AMN组系膜增生、系膜区及内皮下电子致密物出现的百分比高于IMN组（P < 0.01）。(3)AMN和LMN组肾小球IgG3沉积占优势的百分比分别为78.9%、73.9%；IMN组IgG4沉积占优势的百分比为61.1%，差异均有统计学意义（IMN组与AMN、LMN组比较, P < 0.01）。(4)IMN组常出现IgG和C3在上皮下的共沉积现象，而在AMN和LMN组中少见。(5)在鉴别LMN和IMN的指标中，敏感性较高的有肾小球IgG4不占优势（91.3%）；特异性较高的有内皮下电子致密物（100.0%）、血抗SSA抗体（95.5%）、肾小球IgG3占优势（94.4%）。 结论 AMN的临床表现与IMN类似，而各项病理学特点，尤其是肾小球IgG亚型沉积特点与LMN更为接近。它有可能是狼疮肾炎中较为隐匿的一个亚型。     

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.     

Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy

1. Download : Download high-res image (359KB)
2. Download : Download full-size image