Validation of renal biopsy phospholipase A2 receptor staining on direct immunofluorescence in the diagnosis of primary membranous glomerulonephritis

Background: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.

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Successful foetal outcome in a patient with primary membranous nephropathy and circulating anti-phospholipid antibodies: A case report

10.33118/oaj.rep.2019.01.002 ◽

2018 ◽

Keyword(s):

Nephrotic Syndrome ◽

Phospholipase A2 ◽

Membranous Nephropathy ◽

Membranous Glomerulonephritis ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Phospholipase A2 Receptor ◽

Foetal Outcome ◽

Circulating Autoantibodies ◽

Patient’S History

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

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SP055DIAGNOSTIC VALUE OF PHOSPHOLIPASE A2 RECEPTOR, IGG4, ALDOSE REDUCTASE AND SUPEROXIDE DISMUTASE IN DETERMINATION OF PRIMARY VERSUS SECONDARY MEMBRANOUS GLOMERULONEPHRITIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv188.18 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii398-iii398

Author(s):

Kang Wook Lee ◽

Yoo Hyung Kim ◽

Sarah Chung ◽

Dae Eun Choi ◽

Ki Ryang Na ◽

...

Keyword(s):

Superoxide Dismutase ◽

Phospholipase A2 ◽

Aldose Reductase ◽

Membranous Glomerulonephritis ◽

Phospholipase A2 Receptor

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Secondary membranous nephropathy in a patient with myasthenia gravis without thymic disease, and partial remission induced by adrenocorticotropic hormone therapy

SAGE Open Medical Case Reports ◽

10.1177/2050313x19869764 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1986976 ◽

Cited By ~ 1

Author(s):

Ramy M Hanna ◽

Farid Arman ◽

Umut Selamet ◽

William D Wallace ◽

Marina Barsoum ◽

...

Keyword(s):

Myasthenia Gravis ◽

Phospholipase A2 ◽

Adrenocorticotropic Hormone ◽

Case Reports ◽

Membranous Glomerulonephritis ◽

Autoimmune Disorders ◽

African American Female ◽

Phospholipase A2 Receptor ◽

Secondary Membranous Nephropathy ◽

Receptor Antibodies

Membranous glomerulonephritis is the most common glomerular disease in adults. Its primary form has been characterized with formation of phospholipase A2 receptor antibodies. Malignancy, infections, and autoimmune disorders are the most common causes of secondary membranous glomerulonephritis. We present a case of a 55-year-old African American female who presented with nephrotic range proteinuria and diagnosed with secondary membranous glomerulonephritis based on distinct pathological features on kidney biopsy and absence of serum phospholipase A2 receptor antibodies. She initially underwent extensive workup for malignancies, infections, and common autoimmune disorders which were all negative. Her proteinuria remained resistant to steroid treatment and she was treated with subcutaneous adrenocorticotropic hormone injections. Meanwhile, she was also diagnosed with the anti-muscle specific kinase antibody variant of myasthenia gravis. In literature, there are few case reports of myasthenia gravis as a cause of secondary membranous glomerulonephritis. In our case, the lack of other inciting factors also suggested this association.

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Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050538 ◽

2019 ◽

Vol 31 (1) ◽

pp. 208-217 ◽

Cited By ~ 9

Author(s):

Peter D. Burbelo ◽

Megha Joshi ◽

Adrija Chaturvedi ◽

Dustin J. Little ◽

John S. Thurlow ◽

...

Keyword(s):

Serum Albumin ◽

Phospholipase A2 ◽

Healthy Volunteers ◽

Renal Biopsy ◽

Department Of Defense ◽

Membranous Nephropathy ◽

Healthy Controls ◽

Serum Samples ◽

Phospholipase A2 Receptor ◽

Nephrotic Range Proteinuria

BackgroundCirculating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN.MethodsUsing the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status.ResultsAnalysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71–821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent.ConclusionsCirculating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.

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Primary membranous glomerulonephritis with negative serum PLA2R in haemophilia A successfully managed with rituximab – case report and review of the literature

BMC Nephrology ◽

10.1186/s12882-021-02475-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Nicholas Meyer ◽

Wendy Cooper ◽

Paul Kirwan ◽

Roger Garsia ◽

Scott Dunkley ◽

...

Keyword(s):

Renal Biopsy ◽

Membranous Nephropathy ◽

Treatment Strategies ◽

Membranous Glomerulonephritis ◽

Sudden Onset ◽

Haemophilia A ◽

Electron Microscopic ◽

Hiv Coinfection ◽

Phospholipase A2 Receptor ◽

Wide Range

Abstract Background Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause a wide range of glomerular pathologies. In people with haemophilia, transfusion-associated infections with these viruses are common and definitive pathological diagnosis in this population is complicated by the difficulty of safely obtaining a renal biopsy. Membranous nephropathy (MN) is a common cause of adult onset nephrotic syndrome occurring in both primary and secondary forms. Primary MN is associated with podocyte autoantibodies, predominantly against phospholipase A2 receptor (PLA2R). Secondary disease is often associated with viral infection; however, infrequently with HIV or HCV. Distinguishing these entities from each other and other viral glomerular disease is vital as treatment strategies are disparate. Case presentation We present the case of a 48-year-old man with moderate haemophilia A and well-controlled transfusion-associated HCV and HIV coinfection who presented with sudden onset nephrotic range proteinuria. Renal biopsy demonstrated grade two membranous nephropathy with associated negative serum PLA2R testing. Light and electron microscopic appearances were indeterminant of a primary or secondary cause. Given his extremely stable co-morbidities, treatment with rituximab and subsequent angiotensin receptor blockade was initiated for suspected primary MN and the patient had sustained resolution in proteinuria over the following 18 months. Subsequent testing demonstrated PLA2R positive glomerular immunohistochemistry despite multiple negative serum results. Conclusions Pursuing histological diagnosis is important in complex cases of MN as the treatment strategies between primary and secondary vary significantly. Serum PLA2R testing alone may be insufficient in the presence of multiple potential causes of secondary MN.

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