Abstract: FR-PO0686
A Paradoxical Case of Phospholipase A2 Receptor Antibody Seropositivity with NELL-1 Membranous Nephropathy
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Singh, Aditi, Johns Hopkins University, Baltimore, Maryland, United States
- Alahmadi, Ziad, Johns Hopkins University, Baltimore, Maryland, United States
- Wilkins, Reid C., Johns Hopkins University, Baltimore, Maryland, United States
- Koirala, Abbal, Johns Hopkins University, Baltimore, Maryland, United States
Introduction
The detection of anti-phospholipase A2 receptor (PLA2R) antibody (ab) via indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) has revolutionized the diagnosis and management of patients with membranous nephropathy (MN). We report a challenging case of MN with high serum anti-PLA2R ab with kidney biopsy showing neural epidermal growth factor-like 1 (NELL-1) staining.
Case Description
A 70-year-old African American female with a history of recurrent strokes and unintentional weight loss presented with worsening dyspnea and edema. Evaluation revealed acute kidney injury (serum creatinine 2.4 mg/dl; baseline 1.2mg/dl), hypoalbuminemia (1.9g/dl), and thrombocytosis (850,000/mm3). Imaging showed bilateral pulmonary emboli, left renal vein thrombus, and stigmata of volume overload. Urinalysis demonstrated 3+ protein, 9 RBC/HPF, urine albumin creatinine ratio 3.9 g/g, and urine protein creatinine ratio 11.5 g/g. Workup for myeloproliferative disorder mutations was negative. Serologies showed high titer anti-PLA2R ab (>1500RU/ml) by both IIF and ELISA. Kidney biopsy revealed MN with few glomeruli showing collapsing features with immunofluorescence showing positive NELL-1 and negative PLA2R staining, consistent with NELL-1-associated MN. (Fig-1) She received rituximab 1000 mg, diuresis, and angiotensin receptor blockade. Repeat anti-PLA2R ab remained strongly positive (1457RU/ml). There was suspicion of underlying malignancy, however her course was complicated by septic shock from Staphylococcus aureus bacteremia, and family pursued comfort care.
Discussion
Seropositive anti-PLA2R ab with negative glomerular staining has been reported, with increased detection by laser microdissection/mass spectrometry. (LD/MS) However, discordant anti-PLA2R ab staining with NELL-1 staining on biopsy, confirmed by LD/MS, has not been reported. The significance of circulating anti-PLA2R ab in our case is unknown. Our case highlights the current limitations of serum antibody testing for MN and the continued need for a kidney biopsy for its diagnosis and classification.