PLA2R-positive membranous nephropathy in IgG4-related disease

Abstract

Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases.

Case presentation: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy.

Conclusions: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Keywords: IgG4-related Disease; PLA2R-positive membranous nephropathy.

Fig. 1

On FDG PET-CT hyperaccumulation was observed in the left lung and right pleura (A). Light microscopy of the resected lung tumor shows lymphoplasmacytic proliferation, and storiform fibrosis on intervening stroma. HE staining, original magnification × 100 (B). Immunohistochemistry microscopy showed IgG4-positive plasma cells in the specimen,IgG4/IgG ratio 0.81. IgG4 staining, original magnification × 200 (C), IgG staining, original magnification × 200 (D)

Fig. 2

Kidney biopsy findings. Light microscopy showed spike appearances in the glomerular base membrane on periodic acid methenamine-silver staining, × 600. Immunofluorescence microscopy was used for IgG heavy chain, PLA2R, and THSD7A, and double immunofluorescence microscopy for IgG heavy chain subclasses IgG1, IgG2, IgG3, IgG4, and PLA2R, original magnification × 400 (Green: IgG heavy chain subclass, Red: PLA2R)

Fig. 3

Electron microscopy (EM) showed mesangial electron dense deposits (EDD), subendothelial EDD, increased mesangial matrix, and diffuse foot process effacement, original magnification × 8000 (A). EM showed subepithelial EDD and subendothelial edema, original magnification × 12,000(B)