Age, gender, clinical presentation and laboratory findings were documented in every case. Hui, et al.: C4d in membranous nephropathyĬonsecutive of 48 cases of MN diagnosed on renal biopsy from August 2012 to April 2013 were included in the study. Journal of Laboratory Physicians / Jul-Dec 2014 / Vol-6 / Issue-2 In this study, we try to evaluate the utility of C4d IHC in diagnosis of MN. It binds to the epithelial and endothelial cell surfaces and can be used as a marker of complement activation in MN. The formation of these in situ immune complexes results in activation of complement which generates formation of C4d. MN is characterized by deposition of immune complexes in sub epithelial region of the glomerular capillary wall. In addition to its diagnostic utility, it also adds insight to pathogenesis of MN. Immunohistochemistry (IHC) with C4d has been reported as a novel marker for diagnosis of MN in various published studies. In the absence of availability of fresh tissues or absence of glomeruli in the frozen tissue, the diagnosis of MN cannot be confirmed. Immunofluorescence (IF) examination is necessary to differentiate from minimal change disease (MCD) where in MN shows granular staining with immunoglobulin G (IgG) and or C3. In such situation Access this article online Quick Response Code: Website: DOI: 10.4103/0974-2727.141500 However, in early membranous cases, the membrane thickening and spikes may not be obvious. The diagnosis is based on clinical features and characteristic light microscopic findings of diffuse thickening of glomerular capillary wall. Of these, MN is the most common cause of nephrotic syndrome in adults accounting for 20-30% cases.
He differential diagnosis of membrane thickening in renal biopsies includes primary and secondary membranous nephropathy (MN), diabetic nephropathy and amyloidosis. Key words: C4d, complement activation, immunohistochemistry, membranous nephropathy Conclusion: C4d is a reliable method to establish the diagnosis of MN and also a sensitive marker of complement activation reflecting the pathogenesis of MN. All the cases showed diffuse positivity for C4d along the GBM. In 11 cases the capillary loops were rigid but spikes were not seen and in 9 cases there was no apparent thickening of the basement membrane. The glomerular basement membrane (GBM) was diffusely thickened with formation of spikes in 28 cases. Results: There were 25 cases of idiopathic MN, 17 cases of Class V lupus nephritis and 2 cases were secondary to hepatitis C infection with cirrhosis. Immunostaining with C4d was done on paraffin‑embedded sections by polymer‑Horse Radish Peroxidase (HRP) technique using polyclonal antiserum to C4d (Biogenex, India). Fresh frozen tissues were available for IF in 40 cases. The formalin fixed paraffin embedded tissues were stained with routine hematoxylin and eosin stains along with periodic acid‑Schiff and silver methenamine stains to highlight the basement membrane. Materials and Methods: A total 48 cases of MN diagnosed on renal biopsy were analyzed. In the absence of fresh frozen tissue for IF, immunohistochemistry with C4d aids in the diagnosis. In early MN, the light microscopic findings may be difficult to differentiate from minimal chain disease. The diagnosis is based on characteristic light microscopic, electron microscope and immunofluorescence (IF) findings.
Megha S Uppin, E‑mail: ĪBSTRACT Background: Membranous nephropathy (MN) is the most common cause of nephropathy in adults. C4d immunohistochemistry in membranous nephropathy Monalisa Hui, Megha S Uppin, Aruna K Prayaga, Sree Bhushan Raju1, Liza Rajasekhar2 Departments of Pathology and 1Nephrology, and 2Rheumatology Nizam’s Institute of Medical Sciences, Hyderabad, Andhra Pradesh, IndiaĪddress for correspondence: Dr.