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Diagnostic utility of C4d immunohistochemistry in membranous nephropathy
Bheemanathi Hanuman Srinivas1, Norton Stephen2, Priyamvada Ps3
1Additional Professor, Department of Pathology, JIPMER Puducherry, India.
Objectives:
Membranous nephropathy (MN), also called membranous glomerulopathy, is one of the leading causes of nephrotic syndrome in adults which is defined by the presence of subepithelial immune complex deposits with a spectrum of changes in the glomerular basement membrane (GBM). It is known that C4d is a byproduct of the classic and lectin pathway. There is deposition of C4d noted in the cases of immune complex-mediated glomerulonephritis involving the classical/lectin pathway including MN. The main objective of this study is to assess the utility C4d as an immunohistochemical (IHC) stain in MN.
Materials:
A total of 43 cases of MN (primary & secondary) were taken, and 39 cases of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) were used as the control group. All the relevant data were retrieved from the hospital database. C4d immunohistochemistry was performed in the cases as well as the control group.
Results:
A diffuse continuous staining pattern in the glomeruli was observed in cases of primary MN whereas a discontinuous staining in the glomerulI favors a secondary MN. 26/29 cases of MCD showed positivity in the podocytes. Among the cases of FSGS, 7/10 cases showed positivity in the podocytes with 3 cases showing an associated mesangial blush pattern of staining.
Conclusion:
Very few studies are available demonstrating the importance of C4d IHC in MN. C4d IHC can be a useful adjunct for immunofluorescence, especially in cases of early MN.
Insights
Complement C4d immunohistochemistry (IHC) shows promise as a diagnostic tool for membranous nephropathy (MN). This study found C4d staining patterns can help differentiate primary from secondary MN and aid in diagnosing other glomerular diseases.
Area of Science:
- Nephrology
- Immunopathology
- Diagnostic Pathology
Background:
- Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults, characterized by subepithelial immune deposits and glomerular basement membrane changes.
- C4d, a complement pathway byproduct, is found in immune complex-mediated glomerulonephritis, including MN.
- The diagnostic utility of C4d immunohistochemistry (IHC) in MN requires further investigation.
Purpose of the Study:
- To evaluate the effectiveness of C4d immunohistochemistry (IHC) as a diagnostic marker in membranous nephropathy (MN).
- To assess the correlation of C4d staining patterns with primary versus secondary MN.
- To explore the role of C4d IHC in differentiating MN from other glomerular diseases like minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).
Main Methods:
- A cohort of 43 MN cases (primary and secondary) and 39 control cases (MCD/FSGS) were analyzed.
- C4d immunohistochemistry (IHC) was performed on all studied kidney biopsy samples.
- Clinical and pathological data were retrospectively collected from hospital records.
Main Results:
- Diffuse continuous glomerular C4d staining was observed in primary MN.
- Discontinuous glomerular C4d staining suggested secondary MN.
- C4d positivity was noted in podocytes in 26/29 MCD cases and 7/10 FSGS cases, with some FSGS cases showing mesangial staining.
Conclusions:
- C4d immunohistochemistry (IHC) can serve as a valuable adjunct to immunofluorescence in diagnosing MN.
- Specific C4d staining patterns may help distinguish between primary and secondary MN.
- C4d IHC demonstrates potential utility in the diagnosis of early-stage MN and other glomerular pathologies.
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