scholarly journals Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Qiu-hua Zhang ◽  
Mian Wu ◽  
Zhi-gang Hu ◽  
Xiao-bin Liu ◽  
Biao Huang ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Serum Antibody ◽  
Chinese Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Phospholipase A2 Receptor ◽  
Secondary Membranous Nephropathy ◽  
Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

scholarly journals Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hao-yuan Cui ◽  
Chao Li ◽  
Hang Li ◽  
Yu-bing Wen ◽  
Lin Duan ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Serum Antibody ◽  
Chinese Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Igg Subclass ◽  
Electron Microscopic ◽  
Phospholipase A2 Receptor ◽  
Stage 1

Background. The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods. Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related ( n = 132 ) and PLA2R-unrelated ( n = 25 ) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results. We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass ( P > 0.05 ). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup ( P = 0.044 , P = 0.013 ). PLA2R-related subgroup showed higher IgG4 intensity ( 2.1 ± 0.6 vs. 1.6 ± 0.7 , P = 0.001 ) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015 ) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages ( P > 0.05 ). Conclusions. Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

P0103ANALYSIS OF GLOMERULAR IGG SUBCLASSES SWITCH IN IDIOPATHIC MEMBRANOUS NEPHROPATHY CLASSIFIED BY GLOMERULAR PHOSPHOLIPASE A2 RECEPTOR ANTIGEN AND SERUM ANTIBODY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Haoyuan Cui ◽  
Chao Li ◽  
Hang Li ◽  
Yu-bing Wen ◽  
Xi-wei Yan ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Early Stage ◽  
Serum Antibody ◽  
Stage I ◽  
Chinese Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Igg Subclass ◽  
Phospholipase A2 Receptor ◽  
Positive Rate

Abstract Background and Aims IgG subclass switch phenomenon in early pathological stage of idiopathic membranous nephropathy (IMN) was reported recently. However, the profile of serum anti-phospholipase A2 receptor (PLA2R) antibody and glomerular PLA2R antigen was not reported in previous studies. The objective of our study was to testify whether glomerular IgG subclass switch phenomenon was present in PLA2R-related and PLA2R-unrelated IMN, respectively. Method This was a retrospective study including 157 Chinese patients with biopsy-proven IMN in a tertiary referral hospital between September 2017 and November 2019. IMN patients were classified into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroups. We compared the immunofluorescence intensity of glomerular IgG subclass between two groups among different electron microscopic (EM) stages. Results Positive rate of anti-PLA2R antibody was 56.0% (88/157) and glomerular PLA2R deposition was 75.8% (119/157). The intensity of IgG4 deposition in PLA2R-related group was stronger than that in unrelated group (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001). In stage I, IgG4 showed difference in predominant or co-dominant rate (pre/co rate) between two groups (P = 0.015). IgG4 was predominant in early stage (stage I) of both groups (pre/co rate 97% vs 57%). IgG1 was the less predominant subtype in stage I (pre/co rate 39% vs 43%). Pre/co rate of IgG3 declined with EM stage (P = 0.013). Conclusion IgG subclass switch were not found in PLA2R-related or unrelated IMN. IgG4 was the predominant IgG subtype in all stages of PLA2R-related IMN. The positive rate of glomerular PLA2R antigen was higher than serum PLA2R antibody.

scholarly journals Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Dan Dong ◽  
Ting-ting Fan ◽  
Ying-ying Wang ◽  
Lu Zhang ◽  
Li Song ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Remission Rate ◽  
Meta Analysis ◽  
Negative Group ◽  
Urine Protein ◽  
Positive Group ◽  
Phospholipase A2 Receptor ◽  
Significant Difference

Abstract Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN). Methods A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis. Results Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (− 12.09, − 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate. Conclusion As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

scholarly journals Growth Differentiation Factor-15 as a Predictor of Idiopathic Membranous Nephropathy Progression: A Retrospective Study

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Young Rok Ham ◽  
Chang Hun Song ◽  
Hong Jin Bae ◽  
Jin Young Jeong ◽  
Min-Kyung Yeo ◽  
...  
Keyword(s):  
Renal Function ◽  
Disease Progression ◽  
Membranous Nephropathy ◽  
Receiver Operating Curve ◽  
Idiopathic Membranous Nephropathy ◽  
Cox Regression Analysis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Secondary Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. No biomarker to predict the long-term prognosis of IMN is currently available. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzyme-linked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16–72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p=0.007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p=0.012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p=0.032). In conclusion, the GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.

scholarly journals MO270PROGNOSTIC ROLE OF ANTI-PHOSPHOLIPASE A2 RECEPTOR ANTIBODY NEGATIVIZATION AT THREE MONTHS IN MEMBRANOUS NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gabriel Stefan ◽  
Simona Stancu ◽  
Otilia Popa ◽  
Adrian Dorin Zugravu ◽  
Nicoleta Petre ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Albumin ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Immunosuppressive Treatment ◽  
Renal Outcome ◽  
Renal Survival ◽  
Receptor Antibody ◽  
Cox Proportional Hazard ◽  
Phospholipase A2 Receptor

Abstract Background and Aims The predictive value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) levels at three-months from diagnosis in patients with membranous nephropathy (MN) is not proven. Method We retrospectively examined the renal outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, serum creatinine 1.0 (0.9, 1.3) mg/dL) who were diagnosed with MN by kidney biopsy and had positive serum anti-PLA2R ab during 2016-2019. The outcomes were: kidney survival defined as renal replacement therapy (RRT) initiation; partial (proteinuria 0.5 to 3.5g/24h) or complete remission (proteinuria &lt;0.5g/24h and serum albumin ≥3.5g/dL) - whichever came first. Variables related to renal outcome were further evaluated in univariate and multivariate Cox proportional hazard (CPH) models. Results Forty (69%) patients had negative anti-PLA2R ab at 3 months; there were no differences regarding age, serum creatinine, serum albumin, proteinuria and treatment when compared to the group with positive ab at 3 months. Fifty-seven (97%) patients received immunosuppressive treatment, cyclophosphamide-based regimens were the most frequent (87%), followed by cyclosporine (10%). Overall, 64% of the patients reached a form of remission. Cumulative remission rates were 34% after 6 months, 54% after 12 months, 68% after 18 months and 73% after 24 months. Only five patients (9%) relapsed during the study period. Median time to cumulative remission was 12.0 (95%CI 8.2, 15.7) months. In the CPH models, negativization of the anti-PLA2R antibodies at three months was an independent predictor for remission, however lower serum albumin was also retained as a risk factor for absence of remission (Table 1). During the follow up period 6 (10%) patients died. Cardiovascular disease and infections were the main causes of death. A total of 5 (9%) patients started RRT during the study period. The mean renal survival time was 50.3 (95%CI 46.5, 54.0) months. We found no difference in renal survival regarding anti-PLA2R Ab titer or negativization. Conclusion Negativization of anti-PLA2R antibodies in the first three months from diagnosis was a predictor for remission in patients with membranous nephropathy.

scholarly journals PLA2R1 and HLA-DQA1 gene variations in idiopathic membranous nephropathy in South China

2021 ◽  
Vol 50 (1) ◽  
pp. 33-41
Author(s):  
Fan Wang ◽  
Ting-Ting Wang ◽  
Xiao-Wan Liang ◽  
Jian-Da Lu ◽  
Qiong-Hong Xie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Spontaneous Remission ◽  
Idiopathic Membranous Nephropathy ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies ◽  
Chinese Han ◽  
Phospholipase A2 Receptor ◽  
Hla Dqa1

ABSTRACT Introduction: Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population. Methods: A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed. Results: We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction (P>0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission. Conclusion: This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN. Keywords: HLA-DQA1, idiopathic membranous nephropathy, PLA2R1, susceptibility, spontaneous remission

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