Nonlupus Full-House Nephropathy with Phospholipase A2 Receptor (PLA2R) Positivity: A Hybrid Treatment Approach

Introduction: Membranous nephropathy (MN) represents a common cause of nephrotic syndrome in adults and is typically classified as either primary often associated with anti-PLA2R antibodies or secondary to systemic conditions. A hallmark of lupus nephritis is the “full-house” immunofluorescence staining pattern, in which all major immunoglobulins and complement components are present. However, this pattern can occasionally be observed in patients without systemic lupus erythematosus, creating diagnostic ambiguity. Non-lupus full-house nephropathies blur the line between primary and secondary MN, complicating treatment decisions. Case Description: A 52-year-old male with a history of hypertension and remote chronic NSAID use was referred for evaluation of elevated serum creatinine and nephrotic-range proteinuria. Initial labs revealed a creatinine of 2.8 mg/dL and urine albumin-creatinine ratio (uACR) ~9 g/g. A kidney biopsy in March 2024 demonstrated an immune complex-mediated glomerulopathy with a membranous pattern of injury. Electron microscopy revealed diffuse subepithelial electron-dense deposits with spike formation and diffuse foot process effacement. Immunofluorescence showed a full-house pattern (4+ IgG, 3+ C1q, 2+ IgA, 2+ C3, 1+ IgM),raising concern for lupus nephritis. However,serologic tests including ANA, anti-dsDNA, complements, and tissue ANA were negative. There was no monoclonal protein detected by repeat SPEP/IFE. Imaging and malignancy screening were unremarkable. Low-titer PLA2R antibodies were detected. Due to the uncertain etiology, a hybrid treatment strategy was employed, consisting of prednisone, mycophenolate mofetil and rituximab, all initiated concurrently in mid-2024. The patient showed a favorable response with creatinine improving to 1.1 mg/dL and uACR decreasing to 500 mg/g. Prednisone was tapered, and MMF was continued. Discussion: This case highlights a rare presentation of PLA2R-positive MN with full-house immunofluorescence in the absence of SLE or secondary causes. Literature reports describe a minority of such cases eventually developing lupus, necessitating close follow-up. The presence of full-house staining without clinical SLE features suggests an atypical immune response rather than definitive lupus nephritis. Our patient benefitted from a tailored approach combining lupus-oriented immunosuppression and B-cell depletion.