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Use of C4d as a diagnostic tool to classify membranoproliferative glomerulonephritis
Nirupama Gupta1, Dara N Wakefield2, William L Clapp2
1Division of Nephrology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Background:
Membranoproliferative glomerulonephritis (MPGN type I, II and III) was reclassified in 2013 as MPGN and C3 glomerulopathy (C3G) based on the complement system activation mechanism.
Objectives:
To evaluate whether C4d, a component of the classical pathway, could be a diagnostic tool in differentiating between MPGN and C3G.
Methods:
We conducted a retrospective study of 15 MPGN type I, II and III and 13 minimal change disease (MCD) patients diagnosed between 2000 and 2012. C4d staining using the peroxidase method was employed.
Results:
Using the 2013 C3G consensus classification, the 15 MPGN types I, II and III biopsies were re-classified as MPGN (8) and C3G (7). Following C4d staining, of the 8 biopsies diagnosed as MPGN, 4 had classical pathway involvement [C1q (+), C3 (+), C4d (+)]; two had lectin pathway involvement [C1q (-), C3 (+), C4d (+)]; and, two were reclassified as C3G because the absence of C4d and C1q suggested the presence of the alternative pathway [C1q (-), C3 (+), C4d (-)]. Three of the seven C3G biopsies presented classical pathway involvement and were reclassified as MPGN. The alternative pathway was present in one of the other 4 biopsies considered to be C3G. Two C3G biopsies involved the lectin pathway and the one case of dense deposit disease had lectin pathway involvement.
Conclusions:
C4d staining may help to differentiate between MPGN and C3G. In addition, the lectin pathway could play a role in the pathogenesis of these glomerulopathies.
Insights
C4d staining can help differentiate between membranoproliferative glomerulonephritis (MPGN) and C3 glomerulopathy (C3G). The lectin pathway may also play a role in the development of these kidney diseases.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Membranoproliferative glomerulonephritis (MPGN) types I, II, and III were reclassified in 2013 into MPGN and C3 glomerulopathy (C3G) based on complement system activation.
- Understanding the specific complement pathways involved is crucial for accurate diagnosis and treatment.
Purpose of the Study:
- To investigate C4d staining as a diagnostic tool to distinguish between MPGN and C3G.
- To explore the role of different complement pathways in MPGN and C3G pathogenesis.
Main Methods:
- Retrospective analysis of 15 MPGN (types I, II, III) and 13 minimal change disease (MCD) patient biopsies diagnosed between 2000 and 2012.
- C4d deposition was assessed using peroxidase-based staining.
Main Results:
- Re-classification of 15 MPGN biopsies into MPGN (8) and C3G (7) using 2013 criteria.
- C4d staining revealed classical pathway involvement in some MPGN and C3G cases, while others indicated alternative or lectin pathway activation.
- Three C3G biopsies were reclassified as MPGN due to classical pathway markers; one C3G involved the alternative pathway; two C3G and one dense deposit disease case showed lectin pathway involvement.
Conclusions:
- C4d staining shows potential as a diagnostic marker for differentiating MPGN from C3G.
- The lectin complement pathway appears to be implicated in the pathogenesis of these glomerulopathies.
