Phospholipase A2 receptor-negative membranous nephropathy presenting as a rare renal manifestation of IgG4-related disease

Abstract

IgG4-related disease is a fibroinflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells affecting multiple organs. Though the most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis, it can rarely present as secondary membranous nephropathy. We present a case of a 75-year-old male with phospholipase A2 receptor-negative membranous nephropathy as an atypical manifestation of IgG4-related disease. The patient presented with nephrotic syndrome and was found to have elevated serum IgG4 levels and IgG4-positive plasma cells in the kidney biopsy. He was successfully treated with corticosteroids and rituximab, resulting in significant improvement in proteinuria and normalization of IgG4 levels. This case highlights the importance of considering IgG4-related disease in patients with phospholipase A2 receptor-negative membranous nephropathy, especially in those with a history of other organ involvement. Early recognition and treatment of IgG4-related disease are crucial to prevent progressive kidney damage and improve patient outcomes.

Keywords: IgG4-related disease; PLA2R-negative; rituximab; secondary membranous nephropathy; tubulointerstitial nephritis.

Figure 1.

Diagnostic features of phospholipase A2 receptor (PLA2R)-negative membranous glomerulonephritis: glomerular basement membrane thickening (Jones silver stain), IgG+ granular peripheral capillary loop immune deposits (IgG immunofluorescence), negative PLA2R (PLA2R immunofluorescence), and subepithelial electron-dense deposits with capillary wall remodeling (electron microscopy (EM)). Additional features of IgG4-related renal disease: glomerular IgG+ deposits and tubulointerstitial IgG+ plasma cells (IgG4 immunoperoxidase stain). EM: 4800× magnification, 5 µm scale bar. Other images: 400× magnification, 50 µm scale bars.