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Anti-Phospholipase A2 Receptor in Nonlupus Patients with Membranous Nephropathy and Crescents
Yiqin Zuo1,2, Livia Barreira Cavalcante3, James Monroe Smelser4
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Introduction:
Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of "primary" membranous nephropathy (MN). Crescents in MN in nonlupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and are postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody.
Methods:
We studied PLA2R staining in nonlupus patients with MN and crescents. Native renal biopsies in 16 nonlupus patients with MN and crescents were stained for PLA2R.
Results:
The patients included 5 women and 11 men, with mean age 61 years and elevated serum creatinine (mean 4.68 mg/dL). Hematuria and proteinuria (mean 4.97 g/day) were documented in 13 patients. Two patients had positive serum anti-GBM antibody. Nine of 11 patients tested for ANCA were positive, with p-ANCA (n = 4), c-ANCA (n = 2), or both (n = 1), with 2 not specified. On average, 27% of glomeruli had crescents. One patient had an initial biopsy with MN, 4 years later had MN with crescent, and 7 years later had rebiopsy with persistent MN with crescents. One patient had ANCA-associated vasculitis, and 5 years later had MN and crescent. The remaining 14 patients had concurrent diagnoses of MN and crescents. PLA2R was positive in 5 cases, 3 with ANCA positivity, 2 with unknown ANCA status, and none with anti-GBM disease. The patient with initial MN preceding crescent was PLA2R positive; the patient with initial ANCA-associated vasculitis preceding MN was PLA2R negative.
Conclusions:
Most patients (64%) presented with concomitant MN and crescents, with rare occurrence of an initial disease process followed later by the second injury. PLA2R was positive in 31% of patients, suggesting most are secondary MN. Further study to determine the cryptic epitopes may shed light on the triggering mechanisms for these rare but unlikely coincidental glomerular injuries.
Insights
In nonlupus patients with membranous nephropathy and crescents, anti-phospholipase A2 receptor (PLA2R) positivity was observed in 31%, suggesting secondary causes. Further research into cryptic epitopes may reveal injury mechanisms.
Area of Science:
- Nephrology
- Immunopathology
- Glomerular Diseases
Background:
- Primary membranous nephropathy (MN) often involves anti-phospholipase A2 receptor (PLA2R) antibodies.
- Crescents in nonlupus MN suggest a secondary injury, potentially involving autoantibodies like anti-neutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM).
Purpose of the Study:
- To investigate PLA2R staining in nonlupus patients presenting with both MN and glomerular crescents.
- To explore the association between PLA2R status and concurrent or sequential glomerular injuries.
Main Methods:
- Analysis of native renal biopsies from 16 nonlupus patients with MN and crescents.
- Immunohistochemical staining for PLA2R on renal biopsies.
Main Results:
- The study included 16 nonlupus patients (11 male, 5 female; mean age 61) with MN and crescents.
- Elevated serum creatinine and proteinuria were common. Two patients had positive anti-GBM antibodies, and 9 of 11 tested were ANCA-positive.
- PLA2R staining was positive in 5 cases (31%), with 3 of these being ANCA-positive. None of the anti-GBM positive patients were PLA2R positive.
Conclusions:
- A significant proportion (64%) of patients presented with concurrent MN and crescents.
- PLA2R positivity in 31% of these cases suggests a higher likelihood of secondary MN.
- Identifying the triggering mechanisms and cryptic epitopes is crucial for understanding these complex glomerular injuries.
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