A case of proliferative glomerulonephritis with monoclonal IgG3κ deposits accompanied by glomerular capillary microaneurysms

Abstract

Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we report a case of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) presenting with multiple glomerular capillary microaneurysms. A 53-year-old woman presented with persistent proteinuria and microhematuria. She had no underlying diseases, such as hematopoietic or lymphoproliferative disorders. A renal biopsy showed diffuse membranoproliferative lesions with foam cell infiltration and multiple microaneurysms of the glomerular capillary on light microscopy. Immunofluorescence analysis showed granular deposits of monoclonal immunoglobulin G3 kappa (IgG3κ), C1q, C3, and C4 in the glomeruli. Electron microscopy revealed different sizes of non-organized electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. In addition, glomerular endothelial cells showed swelling and loss of fenestra or diffuse formation of fenestrated diaphragms, accompanied by irregular thinning of the glomerular basement membrane. Furthermore, immunostaining for CD31 (a marker for endothelial cell) and low-vacuum scanning electron microscopy study identified loss of endothelial cells in microaneurysm, suggesting severe glomerular endothelial cell injury. After a renal biopsy, only the medication for dyslipidemia was continued because there were no physical symptoms, such as edema, and urinary abnormalities continued with stable renal function. Further studies are needed to elucidate the pathogenesis of glomerular capillary injury in PGNMID and clarify the clinical and pathological characteristics of PGNMID with glomerular capillary microaneurysms.

Keywords: Endothelial cell injury; Glomerular capillary; Glomerulonephritis; Immunoglobulin G3 kappa; Microaneurysm.

Fig. 1

Light microscopy findings. As observed by light microscopy (A, C, D: PAM stain; B: PAS stain; A scale bar: 200 µm; B–D, scale bar: 50 µm), the glomeruli show an irregular double contour of the glomerular basement membrane and segmental mesangial proliferative lesions, indicating membranoproliferative glomerulonephritis lesions in the glomeruli. In some glomeruli, multiple glomerular capillary microaneurysms are noted with insudative hyalinosis (arrowheads in B–D, star in D) and foam cell infiltration (arrow in D). In the tubulointerstitium, vacuolar degeneration indicating foam cell differentiation is observed in some tubules (star in A). The interlobular artery shows mild intimal thickening, indicating mild arteriosclerosis (arrow in A)

Fig. 2

Immunofluorescence findings. Immunofluorescence findings (A–L, ×600) show intense mesangial and irregular glomerular capillary staining for IgG. Immunostaining for IgG subclasses (IgG1–IgG4) and immunoglobulin light κ and chains show intense staining of IgG3 and κ chain, indicating monoclonal IgG3κ deposition. The irregular mesangial and glomerular capillary depositions of C1q, C3, and C4 are also noted

Fig. 3

Electron microscopy findings. From the electron microscopy findings (A ×2500; B ×3000; C ×18,000; D ×15,000), mesangial electron-dense deposits (arrow in A) and a few subepithelial (arrowhead in A) and subendothelial (double arrowheads in A) deposits are noted. In glomerular capillaries, endothelial cells show swelling with loss of fenestra (arrowhead in B) and widening of subendothelial space (star in B) with thinning of the glomerular basement membrane (GBM). Platelets (arrow in B) are seen in contact with the endothelium. At high magnification of the glomerular capillary, the endothelial cells have fenestrated diaphragms in the glomerular capillary cross-sections and fenestrae with central point-like structures or knobs, which are known as fenestrated diaphragms in the tangential section of endothelial cells (arrowhead in C and D)

Fig. 4

Characteristic of glomerular capillary microaneurysm. Serial sections (A PAS stain; B Masson’s trichrome stain; scale bar: 20 µm) revealed that three circular microaneurysms (arrows in A) in the tuft are the edges of the large aneurysm (arrow in B). Immunostaining for CD31 (a marker for endothelial cells) with PAS counterstain did not reveal any glomerular endothelial cells in the widening of subendothelial spaces (arrowheads in C). A low-vacuum scanning electron microscopy (LV-SEM) study was performed using the PAM-stained specimen shown in Fig. 1D after removal of the cover glass and staining with platinum blue. The stars in Fig. 1D and D (scale bar: 20 μm) indicate the same microaneurysmal lesion. E and F show highly magnified images of the area indicated by the square in D. LV-SEM analysis revealed duplication of the glomerular basement membrane (GBM) with irregular thinning and swelling of endothelial cells (double arrowheads in E) in the lesions without microaneurysms. Arrowheads in E and F indicate podocytes. Glomerular endothelial cells could not be detected inside the microaneurysm (star in D) surrounded by the GBM. Components of plasma proteins accumulated in the microaneurysms (star in F)