The continual presence of C3d but not IgG glomerular capillary deposition in stage I idiopathic membranous nephropathy in patients receiving corticosteroid treatment

Abstract

Background: Pathologic diagnosis of stage I idiopathic membranous nephropathy (MN-I) requires electron microscopy or immunohistochemistry that shows a glomerular capillary staining pattern of IgG and C3. However, it is not uncommon that renal biopsy did not obtain sufficient material for electron microscopy and that IgG and C3 staining in glomeruli largely lost at biopsy due to corticosteroid treatment. Since C3d is one of the final degradation products of C3 that is more stable in vivo, we determine if C3d staining could be used as a novel immunohistochemical marker for MN-I.

Methods and results: 74 MN-I patients with electron microscopy proven MN-I were examined by immunoperoxidase staining of C3d. Intensive C3d staining was present in glomerular capillary like the staining pattern of IgG and C3 in MN-I. Importantly, in 40 MN-I patients who underwent corticosteroid treatment at biopsy the intensity and glomerular capillary pattern of C3d staining remained largely intact while the staining for IgG had substantially reduced and the pattern of glomerular capillary staining became unrecognizable.

Conclusions: C3d glomerular capillary staining may be a novel marker for pathologic diagnosis of MN-I that is continuously present at biopsy in patient who has received corticosteroid treatment.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2120780075734479.

Figure 1

Glomerular C3d, IgG and C3c staining in MN-I. A, A strong C3d staining was universally present in glomerular capillary. B, The IgG staining in glomeruli showed a predominantly capillary pattern. C, Staining for C3c showing similar capillary pattern but much lesser intensity.

Figure 2

Different pattern of glomerular C3d staining in minimal change disease, m-MsPGN and MN-I. A, C3d staining was seen in part of mesangium in minimal change disease. B, The mesangial staining was more obvious in m-MsPGN. C, Staning for C3d showed predominantly capillary pattern in MN-I.

Figure 3

Glomerular IgG, C3d, and C3c staining in MN-I after corticoid treatment. A,D, IgG in biopsy samples from patients treated with and without corticosteroid, respectively. B,E, C3c staining pattern treated with and without corticosteroid, respectively. C,F, C3d in MN-I treated with and without corticosteroid, respectively.

Figure 4

C3d immunohistochemical staining in serial sections of paraffin-embedded tissue of MN-II. A. PAM-Masson stain. B. The same region with A, with high-pressure heating plus trypsin retrieval, C3d staining was strongly positive in capillary loop, no backgroud. C3d was also positive in the global sclerotic glomerulus. C. With high-pressure heating plus trypsin retrieval, primary antibody was replaced by PBS as negative control. D. With no antigen retrieval, C3d was faintly positive. E. The negative control with no antigen retrieval. F. With trypsin retrieval, C3d was weakly positive. G. The negative control with trypsin retrieval. H.With high-pressure heating retrieval, C3d was moderately positive. I. The negative control with high-pressure heating retrieval.