The intensity of PLA2R and C4d immunoexpression in primary membranous nephropathy

Abstract

Objective: Antibodies against the phospholipase A2 receptor (PLA2R) on podocyte membranes result in the formation of immune complexes that cause loss of function of the glomerular basement membrane in primary membranous nephropathy (PMN). It has also been demonstrated that there is a deposition of complement 4d (C4d) in the glomeruli in PMN. The present study aims to evaluate PLA2R and C4d immunoexpressions in PMN cases and search the correlation with the clinical parameters. Methods: In this study, clinicopathological data and paraffin-embedded specimens were collected from 51 patients. The formalin-fixed paraffin-embedded tissues were stained using routine hematoxylin-eosin, periodic acid-Schiff, and silver methenamine stains and immunostained for anti-PLA2R and C4d. Ten normal kidney tissues and 10 focal segmental glomerulosclerosis (FSGS) cases were selected as controls for PLA2R and C4d immunoexpression. Results: Of the PMN cases, 51 (100%) cases were positive for PLA2R, including 15 (29%) cases that scored 2+, and 36 (71%) cases that scored 3+. Forty of the 51 cases (78%) were positive for C4d. The percentages of cases staining positively for C4d, per scoring group, were as follows: 31 (61%) cases faintly (1+) positive and 9 (18%) cases moderately (2+) positive. No strong positivity was observed. All of the control cases (100%) were negative for PLA2R and C4d. There was no statistically significant difference between the intensity of the staining of PLA2R and the staining of C4d, proteinuria levels, creatinine levels, and complement 3 (C3) positivity. Similarly, there was no statistically significant difference between the intensity of the staining of C4d and proteinuria levels, creatinine levels, and C3 positivity. Conclusion: Immunohistochemical detection of PLA2R and C4d is a safe and easy method for the diagnosis of PMN. In cases where fresh tissue is not available for the detection of IgG and C3 using the immunofluorescence method, positivity for PLA2R and C4d with immunohistochemistry may be beneficial for the diagnosis of PMN.

The diagnostic value of immunohistochemical staining of the interstitial vascular C4d complement in membranous nephropathy

“…Patients with kidney failure at diagnosis, glomerulosclerosis, high rate of proteinuria, vascular damage and tubulointerstitial fibrosis are connected with poor prognosis [2]. The deposition The diagnostic value of immunohistochemical staining of the interstitial vascular C4d complement in membranous nephropathy of the immune complex at the outer layer of the glomerular basement membrane (GBM), which in turn disturbs the functionality of the glomerular filtration barrier and results in proteinuria has been documented as the main hallmark of MGN [3][4][5]. This in situ antibody deposition occurs in response to the presence of antigens in podocytes, of which the M-type phospholipase A2 receptor (PLA2R) is the main antigen involved in almost all cases of primary MGN [6].…”