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https://www.readbyqxmd.com/read/28904948/recent-progress-in-deciphering-the-etiopathogenesis-of-primary-membranous-nephropathy
#1
REVIEW
Andreas Kronbichler, Jun Oh, Björn Meijers, Gert Mayer, Jae Il Shin
Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50-100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904430/immunohistochemical-analysis-of-anti-phospholipase-a2-receptor-antibody-on-renal-biopsies-a-single-tertiary-care-center-study
#2
A Gudipati, M S Uppin, R K Kalidindi, G Swarnalatha, U Das, G Taduri, S B Raju, L Rajasekhar, Aruna K Prayaga
Membranous nephropathy (MN) is one of the common cause of nephrotic syndrome. The discrimination between primary MN (iMN) and secondary MN is essential because of treatment implications. Immunohistochemical (IHC) evaluation with the help of anti-phospholipase A2 receptor (PLA2R) antibody helps in tissue evaluation of iMN, which is an easy, cost-effective, and pathologist-friendly technique. The study included 82 cases of MN over a period of 3 years. IHC using PLA2R antibody was performed on iMN and secondary cases with adequate tissue...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28891307/a-comprehensive-narrative-review-of-diagnostic-biomarkers-in-human-primary-membranous-nephropathy
#3
Shiva Kalantari, Mohsen Nafar
Membranous nephropathy (MN) is relatively major cause of nephrotic syndrome in adults which is recognized as an organ-specific autoimmune disease. The etiology of most cases is idiopathic, whereas the secondary MN is caused by systemic autoimmune diseases, infections, medications and malignancies. The idiopathic disease is developed by the formation of sub-epithelial immune complex deposits most likely due to binding the circulating auto-antibodies to intrinsic antigen on podocytes. The major auto antibody is the anti-phospholipase A2 receptor (anti-PLA2R), however, it is not enough sensitive...
September 11, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28875476/treatment-of-primary-membranous-nephropathy-where-are-we-now
#4
REVIEW
Andrea Angioi, Nicola Lepori, Ana Coloma López, Sanjeev Sethi, Fernando C Fervenza, Antonello Pani
In the last 10 years, basic science and clinical research have made important contributions to the understanding and management of primary membranous nephropathy (MN). The identification of antibodies directed against the M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A protein have added a new perspective on diagnosis, monitoring the immunological activity, predicting prognosis and guiding therapy in patients with primary MN. Mounting evidence suggests that quantification and follow-up of antiPLA2R Abs levels can help in assessing prognosis and evaluate the response to treatment...
September 5, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28801527/circulating-antibodies-against-thrombospondin-type-i-domain-containing-7a-in-chinese-patients-with-idiopathic-membranous-nephropathy
#5
Jia Wang, Zhao Cui, Jie Lu, Christian Probst, Yi-Miao Zhang, Xin Wang, Zhen Qu, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Hanna Debiec, Pierre Ronco, Ming-Hui Zhao
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...
August 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28789767/-primary-membranous-nephropathy-presenting-as-relapsing-ascites
#6
Kristine Lindhard, Martin Egefjord, Otto Clemmesen
Ascites is common in patients with liver cirrhosis. It may present as a clinical manifestation in nephrotic syndrome in adults, typically with heart- or liver disease together with other oedema. We describe a 64-year-old male patient - with no liver or heart disease - with relapsing ascites and no other oedema, who was surprisingly diagnosed with primary membranous nephropathy (MN), and the autoantibody anti-PLA2R was positive. Through immunotherapy the ascites disappeared. Anti-PLA2R and anti-TSHD7A can be used in the diagnosis (primary/secondary MN) and may play a role in the treatment and prognosis...
July 24, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28761153/pla2r-binds-to-the-annexin-a2-s100a10-complex-in-human-podocytes
#7
Maryline Fresquet, Thomas A Jowitt, Edward A McKenzie, Matthew D Ball, Michael J Randles, Rachel Lennon, Paul E Brenchley
Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family found in podocytes in human kidney. PLA2R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA2R autoantibodies which bind to the podocyte. However the function of PLA2R in health and in disease remains unclear. To gain insight into the molecular mechanisms of PLA2R function, we searched for its endogenous binding partners. Proteomic analysis identified annexinA2 as a potential interactor with the extracellular domains of PLA2R...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745685/-membranous-nephropathy-in-a-russian-population
#8
V A Dobronravov, D A Mayer, O V Berezhnaya, S V Lapin, A V Mazing, V G Sipovsky, A V Smirnov
AIM: To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy. MATERIAL AND METHODS: MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed...
2017: Terapevticheskiĭ Arkhiv
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
#9
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
#10
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
#11
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...
September 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#12
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...
September 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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