Clinicopathological characteristics of M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy in Japanese

Hayashi, Norifumi; Akiyama, Shin–ichi; Okuyama, Hiroshi; Matsui, Yoshihiko; Adachi, Hisashi; Yamaya, Hideki; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Yokoyama, Hitoshi

doi:10.1007/s10157-014-1064-0

Cited by 31 publications

(30 citation statements)

References 26 publications

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“…However, as shown in this study, because the positivity of anti-PLA2R antibodies is affected by many factors, such as the phase and severity of the disease, and the detection methods, it is not clear whether there is truly a difference in the prevalence of anti-PLA2R antibodies among patients with primary MN based on ethnicity. Interestingly, Hayashi et al reported that serum anti-PLA2R antibodies were positive according to western blot in 12/22 (55%) of the Japanese patients with primary MN while four out of the 10 primary MN patients with no detectable serum anti-PLA2R antibodies had glomerular PLA2R deposits [20]. Thus, 16 patients (73%) were classified in the PLA2R-related group when combined.…”

Section: Discussionmentioning

confidence: 99%

Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Katsumata

Okamoto

Moriyama

et al. 2020

Immunological Medicine

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Section: Discussionmentioning

confidence: 99%

Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Katsumata

Okamoto

Moriyama

et al. 2020

Immunological Medicine

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“…However, IgG4 does not bind C1q and is considered to be unable to activate the classical pathway [26,27]. The presence of IgG1 in early deposits could possibly activate the classical pathway, but C1q deposits are very weak in MN [28]. This suggests that the alternative or lectin pathways might be involved in complement activation.…”

Section: Introductionmentioning

confidence: 99%

Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation

Lateb

Ouahmi

Payré

et al. 2019

Journal of Immunology Research

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The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy (MN). However, the pathogenic role of anti-PLA2R1 autoantibodies is unclear. Our aim was to evaluate the in vitro cytotoxicity of anti-PLA2R1 antibodies mediated by complement. Forty-eight patients with PLA2R1-related MN from the prospective cohort SOURIS were included. Anti-PLA2R1 titer, epitope profile, and anti-PLA2R1 IgG subclasses were characterized by ELISA. Cell cytotoxicity was evaluated by immunofluorescence in HEK293 cells overexpressing PLA2R1 incubated with patient or healthy donor sera in the presence or absence of rabbit complement or complement inhibitors. Mean cytotoxicity of anti-PLA2R1 sera for HEK293 cells overexpressing PLA2R1 was 2±2%, which increased to 24±6% after addition of rabbit complement (p<0.001) (n=48). GVB-EDTA, which inhibits all complement activation pathways, completely blocked cell cytotoxicity, whereas Mg-EGTA, which only inhibits the classical and lectin pathways, highly decreased suggesting a limited role of the alternative pathway. A higher diversity of IgG subclasses beyond IgG4 and high titer of total IgG anti-PLA2R1 were associated with increased cytotoxicity (p=0.01 and p=0.03 respectively). In a cohort of 37 patients treated with rituximab, high level of complement-mediated cytotoxicity was associated with less and delayed remission at month 6 after rituximab therapy (5/12 vs. 20/25 (p=0.03) in 8.5 months±4.4 vs. 4.8±4.0 (p=0.02)). Kaplan-Meier analysis demonstrated that high level of cytotoxicity (≥40%) (p=0.005), epitope spreading (defined by immunization beyond the immunodominant CysR domain) (p=0.002), and high titer of anti-PLA2R1 total IgG (p=0.01) were factors of poor renal prognosis. Anti-PLA2R1 antibodies containing sera can induce in vitro cytotoxicity mediated by complement activation, and the level of cytotoxicity increases with the diversity and the titer of anti-PLA2R1 IgG subclasses. These patients with high level of complement-mediated cytotoxicity could benefit from adjuvant therapy using complement inhibitor associated with rituximab to induce earlier remission and less podocyte injury.

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“…Serum PLA2R antibodies in adult patients with MN have been widely studied by many nephrologists in the North American and European countries[ 7 – 16 ], and the Asian countries including China [ 17 – 21 ], but the data of PLA2R staining, especially accompanied with IgG subclasses staining, in renal biopsy tissues of large series of adult MN patients are relatively limited [ 13 – 17 , 22 ]. In this study, the glomerular deposits of PLA2R and IgG subclasses in a large series of Chinese patients with PMN and SMN were retrospectively studied by using immunofluorescence and immunohistochemical staining, and the potential value of these examinations for differential diagnosis of PMN and SMN was explored.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy

et al. 2016

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Background and objectivesThe research work in the past years showed that detection of phospholipase A2 receptor (PLA2R) antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN) was useful for the differentiation between primary MN (PMN) and secondary MN (SMN), but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort.Design, setting, participants, & measurementsThis study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN), 26 patients with hepatitis B virus-associated MN (HBV-MN), 2 patients with malignancy-associated MN (M-MN) and one patient with IgG4-related MN (IgG4-MN). PLA2R and IgG subclasses in glomerular deposits of these patients were examined by immunofluorescence and/or immunohistochemical staining, and the potential value of the above examinations for differential diagnosis of PMN and SMN was evaluated.ResultsGlomerular PLA2R deposition was present in 92.2% patients with PMN and 7.7% patients with HBV-MN, but none of the patients with LN-MN. Predominant/codominant IgG4 deposition was found in 93.3% patients with PMN and 11.5% patients with HBV-MN, but none of the patients with LN-MN. The two M-MN patients both had glomerular PLA2R and predominant/codominant IgG4 deposition. The one IgG4-MN patient had deeply staining IgG4 but no PLA2R in glomeruli.ConclusionsThe glomerular PLA2R and predominant/codominant IgG4 deposition is frequently observed in Chinese patients with PMN. Immunofluorescence and immunohistochemical staining of renal biopsy tissue for detection of glomerular PLA2R and IgG subclasses deposition can help to distinguish PMN from LN-MN and most of HBV-MN.

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Clinicopathological characteristics of M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy in Japanese

Abstract: Assessments of both serum PLA2R antibodies and PLA2R antigen in glomeruli were more sensitive for the diagnosis of PLA2R-related MN, and among affected Japanese patients, those with dominant IgG4 deposition had worse clinical outcomes.

Cited by 31 publications

References 26 publications

Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Clinical usefulness of anti-M-type phospholipase-A-receptor antibodies in patients with membranous nephropathy and the comparison of three quantification methods

Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation

Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy

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