PMC9877447_01
Histological features of the renal biopsy of case 1. (A) Light microscopy section shows a glomerulus with mesangial expansion and endocapillary proliferation as well as thickening and double contour of capillary walls (periodic acid-methenamine-silver stain). (B) Strong deposition of immunoglobulin (Ig) G, complement C3, and C1q are observed along the glomerular capillary walls by immunofluorescence (IF) staining. The deposition of IgA and IgM was ambiguous. (C) Subendothelial and mesangial electron-dense deposits are shown by electron microscopy. Newly formed glomerular basement membrane (red arrows) and infiltration of macrophages (asterisk) are also observed (left). Small amounts of subepithelial electron-dense deposits (yellow arrows) were also observed (right). (D) IF staining for IgG subclasses demonstrates sole deposition of IgG3. (E) There is no deposition of kappa-light chain by IF staining (left), whereas strong deposition of lambda-light chain is observed (right). (F) Both IF staining for nephritis-associated plasmin receptor (left) and in situ zymography for plasmin activity (right) are positively observed with a similar distribution in a glomerulus. (G) The degree of interstitial fibrosis and tubular atrophy are mild (Masson's trichrome stain).
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F1
One glomerulus showed global sclerosis, while the rest showed diffuse and global MPGN patterns with mesangial expansion, endocapillary proliferation, and thickening and double contour of capillary walls (Figure 1A). Immunofluorescence (IF) staining showed deposition of IgG, complement C3, and C1q mainly along the glomerular capillary walls, whereas the deposition of IgA and IgM was ambiguous (Figure 1B). Non-organized electron-dense deposits (EDD) were found mainly in the subendothelial and mesangial areas on electron microscopy (EM), but small amounts of subepithelial EDD were also observed (Figure 1C). IgG3 deposition was solely observed on IF IgG subclass staining (Figure 1D), and IF staining for light chains demonstrated the deposition of only lambda chains without kappa chains (Figure 1E). Furthermore, glomerular positive staining for NAPlr and plasmin activity were observed on IF staining and in situ zymography, respectively (Figure 1F). The degree of interstitial fibrosis and tubular atrophy was mild (Figure 1G).
PMC9877447_02
Histological features of the first renal biopsy of case 2. Lobulation of a glomerulus accompanied by mesangial and endocapillary proliferation as well as thickening and double contour of capillary walls are shown by light microscopy [(A) periodic acid-Schiff stain]. Immunofluorescence (IF) staining showed strong deposition of immunoglobulin (Ig) G mainly along the glomerular capillary walls. The deposition of IgA and IgM was negative (B). IF staining for IgG subclasses demonstrates sole deposition of IgG3 (C). Strong deposition of lambda-light chain is observed by IF staining (D), which seems to correspond with electron-dense deposits in the mesangial and subendothelial areas shown by electron microscopy. There were also small amounts of subepithelial electron-dense deposits [(E) red arrow]. Positive IF staining for complement C3 (left), nephritis-associated plasmin receptor (NAPlr, middle), and in situ zymography for plasmin activity (right) are shown in the glomerulus. The distribution of positive portion for C3 and NAPlr is different, but that for NAPlr and plasmin activity is similar (F).
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F2
The first renal biopsy showed MPGN pattern with endocapillary proliferation (Figure 2A). IgG was positive mainly along the glomerular capillary walls, whereas that for IgA and IgM was both negative (Figure 2B). IF IgG subclass staining demonstrated sole deposition of IgG3 (Figure 2C). Strong lambda-light chain deposition on IF staining (Figure 2D) and corresponding EDD mainly in the mesangial and subendothelial areas were observed (Figure 2E). There were also small amounts of subepithelial EDD (Figure 2E). NAPlr and plasmin activity was observed in the glomeruli with a similar distribution, but the staining pattern of them was different from that of complement C3 (Figure 2F). Neither fibrils nor powdery deposits were observed under EM, and no EDD were found on TBM.
Histological features of the second renal biopsy of case 2, performed about 3 years after the first. Mesangial proliferation and focal double contour of capillary walls are shown by light microscopy [(A) periodic acid-Schiff stain]. Immunofluorescence staining for complement C3 is positive (left), but both nephritis-associated plasmin receptor (middle) and plasmin activity (right) are negative (B).
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F3
The second renal biopsy was performed about 3 years after the first and showed similar pathological findings to those of the first (Figure 3A), but 5 out of 26 glomeruli were globally sclerotic in LM sections, suggesting the progression of histological chronic lesions. NAPlr and plasmin activity were completely negative at this time (Figure 3B).