Circulating Antipodocyte Antibodies in Membranous Nephropathy: Pathophysiologic and Clinical Relevance

Ronco, Pierre; Dębiec, Hanna; Imai, Hirokazu

doi:10.1053/j.ajkd.2013.03.016

Cited by 7 publications

(4 citation statements)

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“…Moreover, in terms of semi-quantitation or quantitation of anti-PLA 2 R, the titers of anti-PLA 2 R determined by RC-IFA in the patient with PMN correlated significantly with the concentrations of anti-PLA 2 R by ELISA (n=82, r=0.696, P<0.001), which was slightly lower than in a previous study [ 10 ]. RC-IFA and ELISA also showed similar specificity, which characterizes anti-PLA 2 R as the serological hallmark for PMN [ 13 ]. On the other hand, it was indicated in the present study that RC-IFA was more sensitive than ELISA, which was consistent with results reported previously [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

Dong

Zhou

et al. 2016

Med Sci Monit

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BackgroundThis study used 2 standardized methods to evaluate anti-PLA2R antibody in sera of Chinese patients with primary membranous nephropathy (PMN) and to determine whether immunological reactivity reflected by antibody titer correlates with kidney function parameters.Material/MethodsOverall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN), 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, and 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China. Anti-PLA2R antibody in the serum of each patient was evaluated by both recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA). Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, and serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameters in the PMN patients.ResultsFifty-three patients with PMN (64.6%) were positive for anti-PLA2R antibody. The level of antibody determined by RC-IFA ranged from 1: 10 to 1: 1000 and 0 to 1423 RU/ml by ELISA. The 2 anti-PLA2R test systems correlated very well with each other and reached an agreement of 95.7% for PMN patients. The level of antibody detected by ELISA in patients with PMN was also significantly correlated with proteinuria and nephritic-range proteinuria (>3.5 g/day).ConclusionsAnti-PLA2R antibody is sensitive and extremely specific for diagnosis of Chinese patients with primary membranous nephropathy. Concentration of autoantibody against PLA2R may be an ideal marker for monitoring the activity of immunological disease.

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Section: Discussionmentioning

confidence: 99%

Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

Dong

Zhou

et al. 2016

Med Sci Monit

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“…It is possible that podocyte over-expression and delocalization of SOD2, and AR may represent an anti-oxidant response preceding the humoral immune response [35]. These characteristics suggest that they are more likely to be neo-antigens exposed aberrantly on cellular surface after the initial podocyte damage, with the consequent production of autoantibodies that could worsen and/or maintain the podocytes complement-mediated damage [36]. In Heymann nephritis, podocyte-produced oxygen radicals in the presence of C5b-9 and mediate glomerular damage.…”

Section: Additional Candidate Antigensmentioning

confidence: 99%

Immunology of membranous nephropathy: from animal models to humans

Sinico

Mezzina

Trezzi³

et al. 2015

Clinical and Experimental Immunology

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SummaryMembranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complementmediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genomewide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

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“…Une explication possible de cette discordance est le fait que PLA2R1 n'est pas le seul antigène cible dans les GEM idiopathiques de l'adulte, mais que HLA-DQA1 pourrait aussi faciliter le développement d'une réponse immune dirigée contre d'autres antigènes. Des anticorps dirigés contre des antigènes cytoplasmiques des podocytes ont été décrits mais leur rôle comme biomarqueurs et dans la pathogénie de la maladie reste à déterminer (Murtas et al, 2013 ;Ronco et al, 2013).…”

Section: Identification De Gènes De Prédisposition à La Gem (( Idiopa...unclassified

Physiopathologie des glomérulopathies extramembraneuses

Ronco

Dębiec

2013

Biologie Aujourd'hui

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Membranous nephropathy (MN) is a kidney disease characterized by deposition of immune complexes and complement on the outer aspect of the glomerular capillary wall. It is responsible for a loss of serum proteins in the urine and kidney failure. During the last ten years, considerable progress has occurred in the understanding of the molecular bases of the disease with the description of three distinct mechanisms in humans. In the neonatal allo-immune form, antibodies are directed against neutral endopeptidase (NEP), a podocyte antigen absent in the mothers who become immunized against this antigen expressed by placenta cells during pregnancy. NEP was the first podocyte antigen to be identified in MN. Most adult forms of MN are autoimmune diseases without identified etiology (primary MN), linked to the production of antibodies raised against another podocyte antigen, the type-M phospholipase A2 receptor (PLA2R1). Anti-PLA2R1 antibodies are detected in 70 to 80% of patients before any immunosuppressive treatment, and only occasionally in secondary forms of MN, variants of PLAR1 and HLA-DQA1 genes are very significantly associated with occurrence of primary MN in Caucasians. The third mechanism is characterized by immunization against a foreign protein, cationic bovine serum albumin (BSA), which is involved in rare forms of MN during early childhood. This finding points to a possible role of food and environmental antigens in membranous nephropathy.

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Circulating Antipodocyte Antibodies in Membranous Nephropathy: Pathophysiologic and Clinical Relevance

Cited by 7 publications

References 50 publications

Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

Anti-PLA2R Antibodies in Chinese Patients with Membranous Nephropathy

Immunology of membranous nephropathy: from animal models to humans

Physiopathologie des glomérulopathies extramembraneuses

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