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https://www.readbyqxmd.com/read/28693446/response-to-immunosuppressive-therapy-in-pla2r-associated-and-non-pla2r-associated-idiopathic-membranous-nephropathy-a-retrospective-multicenter-cohort-study
#1
Jia Wang, Qionghong Xie, Zhuxing Sun, Ningxin Xu, Yan Li, Liang Wang, Shaojun Liu, Jun Xue, Chuan-Ming Hao
BACKGROUND: According to renal M type phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (IMN) could be categorized into PLA2R-associated and non-PLA2R-associated IMN. We conducted a retrospective, multicenter cohort study with 91 patients to compare the effect of immunosuppressive therapy between PLA2R-associated and non-PLA2R-associated IMN patients. METHODS: A total of 91 biopsy-proven IMN patients from Huashan hospital and People's Hospital of Wuxi in past 5 years were collected into this study...
July 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28685717/variants-in-the-promoter-region-of-hla-dqa1-were-associated-with-idiopathic-membranous-nephropathy-in-a-chinese-han-population
#2
Xiao-Song Qin, Jian-Hua Liu, Guan-Ting Lyu, Meng-Le Peng, Fu-Ning Yang, Dong-Chun Qin, Yong-Zhe Li, Yong Liu
BACKGROUND: Idiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population. In this study, six single nucleotide polymorphisms (SNPs) in the promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for the association analysis. METHODS: The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX...
July 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28674044/pla2r-and-thsd7a-disparate-paths-to-the-same-disease
#3
REVIEW
Laurence H Beck
The phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major autoantigens in primary membranous nephropathy (MN), and define two molecular subclasses of this disease. Both proteins are large transmembrane glycoproteins expressed by the podocyte, and both induce IgG4-predominant humoral immune responses that produce circulating autoantibodies that can be used clinically for diagnostic and monitoring purposes. The biologic roles of these proteins remain speculative, although several features of THSD7A suggest a role in adhesion...
July 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#4
REVIEW
Piero Ruggenenti, Fernando C Fervenza, Giuseppe Remuzzi
In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition...
July 3, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28614271/serum-anti-pla2r-antibody-and-glomerular-pla2r-deposition-in-chinese-patients-with-membranous-nephropathy-a-cross-sectional-study
#5
COMPARATIVE STUDY
Lu Pang, Ai-Min Zhang, Hai-Xia Li, Jia-Lin Du, Li-Li Jiao, Nan Duan, Yi Liu, Dan Yu
M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated.A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously measured. We examined serum anti-PLA2R antibody by ELISA and glomerular PLA2R deposition by immunofluorescence assay...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28577748/-membranous-nephropathy-new-insights-in-therapeutic-approach
#6
Karine Dahan
Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, evolving to 30 % end-stage renal disease after 10 years, in the absence of specific treatment. In 2009, the M-type phospholipase A2 receptor (PLA2R), a podocyte membrane glycoprotein, was identified as the first autoantigen involved in more than 70 % of primitive membranous nephropathy. Many studies have reported that high titers of PLA2R antibodies are correlated with a lower risk of spontaneous or immunosuppressant-induced remission, a higher risk of nephrotic syndrome and of progression to end-stage renal disease...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28550082/primary-membranous-nephropathy
#7
William G Couser
Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%)...
June 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28490696/-diagnostic-value-of-renal-phospholipase-a2-receptor-and-serum-anti-phospholipase-a2-receptor-antibody-in-membranous-nephropathy
#8
Xiaoxiang Wu, Si Wen, Xuejing Zhu, Shuguang Yuan, Xiangqing Xu, Danyi Yang, Lin Sun, Hong Liu, Fuyou Liu
To examine the expression of phospholipase 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...
April 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28488220/pla2r-positive-primary-membranous-nephropathy-in-a-child-with-ipex-syndrome
#9
Teresa Chuva, Frederick Pfister, Ortraud Beringer, Kerstin Felgentreff, Maike Büttner-Herold, Kerstin Amann
BACKGROUND: Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency syndrome characterized by the development of multiple autoimmune disorders in affected individuals. Different forms of renal injury have been reported in IPEX syndrome, and membranous nephropathy (MN) is among the most common glomerulopathies found. However, the exact pathogenesis of MN in this setting has not been elucidated, and it is not clear whether it is part of the clinical spectrum of the disease or secondary to medications, infections or other concomitant insults...
May 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28413416/immunohistochemical-glomerular-expression-of-phospholipase-a2-receptor-in-primary-and-secondary-membranous-nephropathy-a-retrospective-study-in-an-indian-cohort-with-clinicopathological-correlations
#10
Sanjeet Roy, Anila Korula, Gopal Basu, Shibu Jacob, Santosh Varughese, Veeraswamy Tamilarasi
BACKGROUND: Limited published literature exists on the utility and standardization of anti-phospholipase A2 receptor (anti-PLA2R) immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy (MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN and clinicopathological correlations in an Indian cohort. METHODS: Subjects included patients with primary and secondary MN diagnosed between January 2012 and August 2014 with an adequate renal biopsy and at least 1 year of clinical follow-up...
January 2017: Nephron Extra
https://www.readbyqxmd.com/read/28397878/a-novel-time-resolved-fluoroimmunoassay-for-the-quantitative-detection-of-antibodies-against-the-phospholipase-a2-receptor
#11
Biao Huang, Liang Wang, Yi Zhang, Jue Zhang, Qiuhua Zhang, Hualong Xiao, Bin Zhou, Zhuxing Sun, Ya-Nan Cao, Yu Chen, Zhigang Hu, Huiming Sheng
A highly sensitive time-resolved fluoroimmunoassay (TRFIA) was developed to quantify serum antibodies against the phospholipase A2 receptor (anti-PLA2R-IgG) for differential diagnosis of membranous nephropathy. Recombinant PLA2R (rPLA2R) was coated onto 96-well plates as a capture. A goat-anti-human IgG tracer was prepared with europium-chelate for detection. After bound/free separation by washing, the fluorescence counts of bound tracer were measured for quantifying serum anti-PLA2R-IgG concentration. A purified anti-PLA2R-IgG calibrator was first prepared for ensuring that consistent quantitative results could be obtained...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397717/renal-phospholipase-a2-receptor-and-the-clinical-features-of-idiopathic-membranous-nephropathy
#12
Ning-Xin Xu, Qiong-Hong Xie, Zhu-Xing Sun, Jia Wang, Yan Li, Liang Wang, Shao-Jun Liu, Jun Xue, Chuan-Ming Hao
BACKGROUND: According to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN. METHODS: A total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28396737/anti-phospholipase-a2-receptor-antibody-levels-at-diagnosis-predicts-spontaneous-remission-of-idiopathic-membranous-nephropathy
#13
Perrine Jullien, Barbara Seitz Polski, Nicolas Maillard, Damien Thibaudin, Blandine Laurent, Edouard Ollier, Eric Alamartine, Gérard Lambeau, Christophe Mariat
Background: The diagnostic role of circulating anti-phospholipase A2 receptor antibodies (anti-PLA2R Abs) is now well recognized in idiopathic membranous nephropathy (iMN). These Abs could also be interesting as predictors of clinical outcome. In this study, we explored the prognostic value of anti-PLA2R Abs measured in a cohort of iMN patients, with a special focus on their ability to detect patients achieving spontaneous remission. Methods: All adult patients with biopsy-proven iMN diagnosed between 1978 and 2007 were retrospectively screened in our centre...
April 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28362702/the-usefulness-of-phospholipase-a2-receptor-and-igg4-detection-in-differentiation-primary-membranous-nephropathy-from-secondary-membranous-nephropathy-in-renal-biopsy
#14
Min-Kyung Yeo, Yoo Hyung Kim, Dae Eun Choi, Song-Yi Choi, Kyung-Hee Kim, Kwang-Sun Suh
Membranous nephropathy (MGN) is the most common cause of the nephrotic syndrome in adults. Most cases of MGN are primary, but secondary MGN are frequently encountered. Determination of secondary MGN is crucial for initiation of appropriate treatment. The diagnostic performance of the phospholipase A2 receptor (PLA2R) and immunoglobulin G4 (IgG4) detection based on immunohistochemistry were evaluated using biopsy tissues of 59 primary and 56 secondary MGN cases for discrimination between primary MGN and secondary MGN...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28340077/idiopathic-non-lupus-full-house-nephropathy-is-associated-with-poor-renal-outcome
#15
COMPARATIVE STUDY
Emilie C Rijnink, Y K Onno Teng, Tineke Kraaij, Ron Wolterbeek, Jan A Bruijn, Ingeborg M Bajema
Background.: Full-house immunofluorescence in combination with various histopathologic lesions in the renal biopsies of patients without overt systemic lupus erythematosus (SLE) poses a diagnostic challenge. In this setting, the biopsy findings are sometimes termed non-lupus 'full-house nephropathy' (FHN). It is presently unknown whether idiopathic non-lupus FHN is clinicopathologically and prognostically distinct from lupus FHN. Methods.: We included non-lupus FHN patients and lupus FHN controls (four or more American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) who were biopsied between 1968 and 2014 at the Leiden University Medical Centre...
April 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28257452/prognostic-value-of-pla2r-autoimmunity-detected-by-measurement-of-anti-pla2r-antibodies-combined-with-detection-of-pla2r-antigen-in-membranous-nephropathy-a-single-centre-study-over-14-years
#16
Franck Pourcine, Karine Dahan, Fabrice Mihout, Marine Cachanado, Isabelle Brocheriou, Hanna Debiec, Pierre Ronco
INTRODUCTION: Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers. METHODS: In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag...
2017: PloS One
https://www.readbyqxmd.com/read/28167276/detection-and-monitoring-pla2r-autoantibodies-by-lips-in-membranous-nephropathy
#17
COMPARATIVE STUDY
Peter D Burbelo, Laurence H Beck, Meryl Waldman
Autoantibodies against the M-type phospholipase A2 receptor (PLA2R) are specific markers for primary membranous nephropathy (MN). Quantification of PLA2R autoantibodies is an important, noninvasive tool that facilitates the diagnosis and monitoring of primary MN. In this report we describe a highly quantitative luciferase immunoprecipitation systems (LIPS) assay for detecting PLA2R autoantibodies. For these studies, a cDNA fragment encoding the first 858 amino acids of PLA2R protein was cloned to generate N-terminal antigen fusion constructs with Gaussia luciferase (Gluc) and Nano luciferase (NanoLuc) reporters...
May 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28065518/membranous-nephropathy-integrating-basic-science-into-improved-clinical-management
#18
REVIEW
Daniel C Cattran, Paul E Brenchley
Idiopathic membranous nephropathy (INM) remains a common cause of the nephrotic syndrome in adults. The autoimmune nature of IMN was clearly delineated in 2009 with the identification of the glomerular-deposited IgG to be a podocyte receptor, phospholipase A2 receptor (PLA2R) in 70% to 75% of cases. This anti-PLA2R autoantibody, predominantly the IgG4 subclass, has been quantitated in serum using an enzyme-linked immunosorbent assay and has been used to aid diagnosis and monitor response to immunosuppressive therapy...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28028136/hla-drb1-15-01-and-hla-drb3-02-02-in-pla2r-related-membranous-nephropathy
#19
Wei-Bo Le, Jing-Song Shi, Tao Zhang, Lei Liu, Hua-Zhang Qin, ShaoShan Liang, Yuan-Wei Zhang, Cun-Xia Zheng, Song Jiang, Wei-Song Qin, Hai-Tao Zhang, Zhi-Hong Liu
Idiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN...
May 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27942609/membranous-nephropathy-pilot-study-of-a-novel-regimen-combining-cyclosporine-and-rituximab
#20
Meryl Waldman, Laurence H Beck, Michelle Braun, Kenneth Wilkins, James E Balow, Howard A Austin
INTRODUCTION: There is broad consensus that high grade basal proteinuria and failure to achieve remission of proteinuria are key determinants of adverse renal prognosis in patients with primary membranous nephropathy. Based on the fact that current regimens are not ideal due to short and long-term toxicity and propensity to relapse after treatment withdrawal, we developed a treatment protocol based on a novel combination of rituximab and cyclosporine which targets both the B and T cell limbs of the immune system...
July 2016: KI Reports
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