False positivity for PLA2R1 antibody measured by ELISA in a nephrotic patient with no membranous nephropathy

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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...     

Negative anti-phospholipase A2 receptor antibody status at three months predicts remission in primary membranous nephropathy

BackgroundThe value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) monitoring at 3 months after diagnosis in membranous nephropathy (MN) remains uncertain.MethodsWe retrospectively examined the outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, SCr 1.0 (0.9, 1.3) mg/dL) diagnosed with MN (kidney biopsy, positive serum anti-PLA2R ab). The outcomes were: kidney survival; partial and/or complete remission.ResultsMost of the studied patients (97%) received immunosuppression, cyclophosphamide regimens were the most frequent (87%), followed by cyclosporine (10%). The median time to remission was 12.0 months and the cumulative remission rates were 34% at 6, 54% at 12, and 73% at 24 months. Forty (69%) patients had negative anti-PLA2R ab at 3 months, they had similar age, serum creatinine, albumin, proteinuria, and treatment with the group with positive ab at 3 months. In the Cox proportional hazard model, three months anti-PLA2R ab negativization (HR 0.4 (95%CI 0.1, 0.9)) was an independent predictor for remission, while baseline hypoalbuminemia (HR 3.0 (95%CI 1.5, 5.7)) was associated with absence of remission. Six (10%) patients died, mostly due to cardiovascular disease and infections. A total of five (9%) patients started dialysis. Mean kidney survival time was 50.3 months and there was no survival difference in relation to baseline anti-PLA2R ab titer (p .09) or 3 months negativization (p .8).ConclusionsThree months anti-PLA2R ab negativization seems to be a late predictor of remission, and lower serum albumin at diagnosis is an early marker for remission absence. Abbreviations: anti-P LA2R ab, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; MN, membranous nephropathy; NELL-1, neural epidermal growth factor-like 1 protein; RAAS: renin–angiotensin–aldosterone system; RBC: red blood cells; RRT, renal replacement therapy; T HSD7A, thrombospondin type-1 domain containing 7A     

Analysis of glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels

ObjectiveTo verify glomerular PLA2R antigen and serum PLA2R antibody expression in membranous nephropathy as well as to explore glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy (IMN) in the background of different serum anti-PLA2R levels.MethodsWe retrospectively analyzed 155 patients who were diagnosed with IMN by kidney biopsy. Patients were divided into six groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum anti-PLA2R titer. Both clinical features and pathological characteristics were recorded, and the remission time was compared among groups. Correlation between clinical figures and the anti-PLA2R titer or semi-quantity of glomerular PLA2R antigen was detected.ResultsA positive correlation between time to partial remission and serum anti-PLA2R titer was found. Among patients with serum anti-PLA2R titer <150 RU/ml, there were shorter remission time in negative glomerular PLA2R antigen group compared with positive glomerular PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of glomerular PLA2R antigen was found.ConclusionBoth glomerular PLA2R antigen and serum anti-PLA2R play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum anti-PLA2R titer is less than 150RU/ml, while serum anti-PLA2R has predominant role in IMN prognosis when serum anti-PLA2R titer is above 150RU/ml.     

Association of serum mannose-binding lectin,anti-phospholipase A2 receptor antibody and renal outcomes in idiopathic membranous nephropathy and atypical membranous nephropathy: a single center retrospective cohort study

ObjectivesIdiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a ‘full-house’ on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN.MethodsWe conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested.ResultsFinally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (−) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (−) patients (p = .045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups.ConclusionsThe complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.     

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients

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

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特发性膜性肾病血栓栓塞并发症的预防与治疗

特发性膜性肾病(IMN)最常见的并发症为静脉血栓和栓塞症,其可对机体造成不同程度的损伤,加剧患者的病情进展,影响预后,严重时甚至可造成患者死亡。但至今为止尚无指导临床用药的可靠实验室指标,也无统一的诊疗规范或措施。本文根据国内、外最新研究进展及相关指南,从预防及治疗的角度,探讨临床上对IMN并发静脉血栓或栓塞的干预方法,并对IMN并发静脉血栓或栓塞治疗过程的监测指标做一概述。     

Characteristics of patients with coexisting IgA nephropathy and membranous nephropathy

Background: Coexistence of IgA nephropathy (IgAN) and membranous nephropathy (MN) in the same patient is rare. Few studies have reported the clinical and pathological features of patients with combined IgAN and MN (IgAN–MN).

Methods: The clinico-pathological features, levels of galactose-deficient IgA1 (Gd-IgA1) and autoantibodies against M-type transmembrane phospholipase A₂ receptor (anti-PLA₂R) in sera were compared among IgAN–MN, IgAN, and MN patients.

Results: Twenty-six patients with biopsy-proven IgAN–MN were enrolled. The mean age at biopsy was 43.6?±?15.9?years, and 65.4% were male. Proteinuria and estimated glomerular filtration rate (eGFR) levels in patients with IgAN–MN were similar to that of MN patients. Compared with the IgAN patients, IgAN–MN patients showed a higher median proteinuria level (4.3 vs. 1.2?g/day, p?2, p?p?=?.801). Percentage of IgAN–MN patients with detectable serum levels of anti-PLA₂R was lower than that of MN patients (38.5% vs. 68.6%, p?=?.011).

Conclusions: IgAN–MN patients display similar clinical features to MN patients and milder pathological lesions than IgAN patients. IgAN–MN patients have similar levels of Gd-IgA1 to those of IgAN patients, and a lower proportion of anti-PLA₂R than MN patients.     

血、尿中PLA2R抗体以及THSD7A抗体在特发性膜性肾病中的临床意义

目的通过检测膜性肾病(MN)患者中血清、尿中M型磷脂酶A2受体(PLA2R)抗体以及1型血小板反应蛋白7A域(THSD7A)抗体浓度,探讨其在特发性膜性肾病(IMN)中的临床意义。 方法选取2015年7月至2017年12月在山西医科大学第二医院肾内科经过肾活检确诊为MN的患者,通过酶联免疫吸附方法(ELISA)测定血清、尿中PLA2R抗体以及THSD7A抗体浓度水平。采用SPSS 21.0软件对数据进行统计分析。 结果经临床、病理确诊为MN的患者189例,其中IMN组165例(87.3%)。(1)IMN患者血清、尿PLA2R抗体的阳性率分别64.8%、60.0%,血清、尿THSD7A抗体的阳性率分别为8.4%、5.4%;(2)IMN患者血清、尿PLA2R抗体浓度与24 h尿蛋白定量呈正相关(P<0.05),与血清白蛋白呈负相关(P<0.05);(3)IMN患者中血清、尿THSD7A抗体浓度与24 h尿蛋白定量呈正相关(P<0.05),与血清白蛋白无相关性(P>0.05);(4)IMN患者中血清PLA2R、抗体浓度与尿PLA2R抗体浓度呈正相关(P<0.05),血清THSD7A抗体浓度与尿THSD7A抗体浓度呈正相(P<0.05)。 结论血清、尿中PLA2R抗体以及THSD7A抗体均可作为IMN诊断的特异性指标,相对于THSD7A抗体而言,PLA2R抗体检出率更高,且这两种抗体在血清、尿中浓度水平与临床指标存在一定的相关性。     

PLA2R、 THSD7A与IgG亚型在特发性膜性肾病中的诊断价值

目的探讨特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者血清抗磷脂酶A2受体(phospholipase A2 receptor,PLA2R)抗体水平、肾小球PLA2R、1型血小板反应蛋白7A域(thrombospondin type I domain containing 7A,THSD7A)、免疫球蛋白G(immunoglobulin G,IgG)亚型的表达及其在IMN中的诊断价值。方法选取2016年1月至2019年6月在雅安市人民医院肾内科经肾活检并确诊的IMN患者72例,以同期72例非IMN肾小球疾病患者为对照。采用酶联免疫吸附法检测血清抗PLA2R抗体滴度,免疫荧光法检测肾小球PLA2R、THSD7A及IgG亚型表达。采用受试者工作特征(ROC)曲线分析血清抗PLA2R抗体、肾小球PLA2R、THSD7A、IgG4诊断IMN的价值。结果血清抗PLA2R抗体、肾小球PLA2R、IgG4、THSD7A诊断IMN的灵敏度分别为61.11%、80.56%、97.22%、8.33%,特异度分别为97.22%、100.00%、97.22%、100.00%。血清抗PLA2R抗体和肾小球PLA2R任一指标阳性即诊断IMN的敏感性为83.33%;肾小球PLA2R、THSD7A和IgG4中任一指标阳性即诊断IMN的敏感性为97.22%。结论血清抗PLA2R抗体、肾小球PLA2R、THSD7A及IgG4亚型对于IMN诊断具有较高的临床价值。血清抗PLA2R抗体及肾小球PLA2R抗原的联合检测,肾小球PLA2R、THSD7A与IgG4的联合检测可以增加IMN诊断的敏感性。     

Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies

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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.     

Assessing risk factors,presentation, and management of portomesenteric vein thrombosis after sleeve gastrectomy: a multicenter case-control study

Background

Portomesenteric vein thrombosis (PMVT) is a rare complication of laparoscopic sleeve gastrectomy.

髋膝关节置换术前预测深静脉血栓形成的多因素分析

[目的]通过对髋、膝关节置换术前患者的相关危险因素的分析,个体化预测其术后下肢深静脉血栓形成(deepveinthrombosis,DVT)的可能性.[方法]2006年4月～2011年11月共309例(髋关节病变113人、膝关节病变196人)接受髋、膝关节置换术的无DVT的患者被纳入研究.所有患者在围术期均接受正规的物理及药物预防血栓治疗.术后第3～10d根据患者病情复查双下肢深静脉彩超了解是否形成血栓.最后,通过术后DVT组与非DVT组的各种术前危险因素的对比分析,提出术前预测术后DVT的公式.[结果]309名患者中术后发生DVT者82例,其中髋关节12例,膝关节70例;单关节置换术后38例,双关节同时置换术后44例.通过判别分析,发现年龄、谷草转氨酶、肌酐、一次手术关节数量、凝血酶原时间和D-二聚体定量与髋、膝关节置换术后DVT的相关性较强,并得出函数预测公式.所有患者平均随访3.5年(4～71个月),均未发生症状性肺栓塞,也未发生明确的肝素类药物副作用.[结论]即使在围术期正规抗凝治疗的前提下,髋、膝关节置换术后DVT的发生率仍然较高.术前如开展个体化预测,能提示对高危人群给予更积极、合理的干预,从而减少术后DVT相关的并发症.