The Usefulness of Phospholipase A2 Receptor and IgG4 Detection in Differentiation Primary Membranous Nephropathy From Secondary Membranous Nephropathy in Renal Biopsy

Yeo, Min‐Kyung; Kim, Yoo Hyung; Choi, Dae Eun; Choi, Song‐Yi; Kim, Kyung‐Hee; Suh, Kwang Sun

doi:10.1097/pai.0000000000000460

Cited by 10 publications

(15 citation statements)

References 29 publications

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“…Based on our results, IHC determination of PLA2R and IgG4 can be associated with improved diagnostic accuracy of primary MN. This is in line with other clinical studies which opined that high expression of IgG4 in patients with idiopathic MN occur in addition to increased expression of PLA2R in renal samples of these patients and may lead to enhance differential power of detection primary and secondary MN [20,26,34].…”

Section: Discussionsupporting

confidence: 91%

“…As indicated by Yeo et al, primary MN can be distinguished from secondary forms through immunohistochemical detection of PLA2R and IgG4 deposits from renal biopsy with acceptable sensitivity and specificity of the test. Simultaneous positivity rates for PLA2R and IgG4 demonstrated an increased specificity in case of primary MN detection [26]. IHC staining has previously been shown to be the most sensitive technique, identifying MN patients correlated with anti-PLA2R antibodies [27].…”

Section: Discussionmentioning

confidence: 99%

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A cohort study of membranous nephropathy, primary or secondary

et al. 2021

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Background Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established. Methods In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined. Results Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%). Conclusions Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A cohort study of membranous nephropathy, primary or secondary

et al. 2021

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“…Five of ten cases tested (50%) demonstrated positive PLA2R staining in the glomerular capillary walls (5/10). Evaluation of IgG subclasses (IgG1-G4) revealed that these PLA2R+ membranous deposits were IgG4 dominant (or codominant), as has been previously described in primary/idiopathic MN [23]. Although serum data was only available in three patients, all with tissuepositivity for PLA2R, only one patient had elevated serum anti-PLA2R antibodies at the time of testing.…”

Section: Discussionsupporting

confidence: 58%

Membranous nephropathy in patients with HIV: a report of 11 cases

et al. 2020

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Background Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied. Methods We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded. Results We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4–145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period. Conclusions MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.

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“…Further studies are needed to discover if the prevalence of anti-PLA2R antibodies is affected by ethnicity or other unknown factors. In a study by Yeo et al [ 26 ], histologic detection of PLA2R showed a sensitivity of 83% and a specificity of 88% in identifying primary MN, and a meta-analysis including about 600 patients with MN showed similar results. Detection of PLA2R in glomeruli and anti-PLA2R antibodies in serum is expected to be more sensitive and specific in discriminating between primary and secondary MN.…”

Section: Discussionmentioning

confidence: 83%

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy

Song

Jeong

Yang

et al. 2018

Kidney Res Clin Pract.

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BackgroundPhospholipase A2 receptor (PLA2R) has been identified as a major autoantigen in primary membranous nephropathy (MN). We evaluated the association between anti-PLA2R antibodies and clinical outcome in Korean patients with primary MN.MethodsA total of 66 patients with biopsy-proven MN were included. Serum level of anti-PLA2R antibodies was measured by enzyme-linked immunosorbent assay. Biochemical parameters were estimated initially and at follow-up.ResultsAnti-PLA2R antibodies were detected in 52.1% and 27.8% of patients with primary and secondary MN, respectively. Forty-eight patients with primary MN were grouped based on presence or absence of anti-PLA2R antibodies. Proteinuria was more severe in anti-PLA2R-positive patients than in anti-PLA2R-negative patients (urine protein/creatinine ratio 7.922 ± 3.985 g/g vs. 4.318 ± 3.304 g/g, P = 0.001), and anti-PLA2R antibody level was positively correlated with proteinuria. The incidence of chronic kidney disease stage ≥ 3 was higher in anti-PLA2R-positive patients compared with anti-PLA2R-negative patients (P = 0.004). The probabilities of spontaneous remission were higher in anti-PLA2R-negative patients compared with anti-PLA2R-positive patients (P < 0.001). Multivariate analysis demonstrated that anti-PLA2R antibodies are an independent risk factor for developing chronic kidney disease stage ≥ 3 and for not reaching spontaneous remission.ConclusionDetection of anti-PLA2R antibodies at diagnosis in patients with primary MN can predict prognosis and guide treatment decisions.

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The Usefulness of Phospholipase A2 Receptor and IgG4 Detection in Differentiation Primary Membranous Nephropathy From Secondary Membranous Nephropathy in Renal Biopsy

Cited by 10 publications

References 29 publications

A cohort study of membranous nephropathy, primary or secondary

A cohort study of membranous nephropathy, primary or secondary

Membranous nephropathy in patients with HIV: a report of 11 cases

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy

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