Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy

Abstract

The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.

Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies

“…Based on the current report and that of Qin et al, 3 it is clear that PLA2R1-positive membranous glomerulopathy can occur in the setting of what would otherwise be considered a secondary etiology. This stands in contrast to the data of Hoxha et al, 5 who report no secondary etiologies in cases with PLA2R1 staining. It should be noted, however, that Hoxha et al provided no detail as to what secondary etiologies were excluded.…”

“…4 Another recent report showed better correlation between tissue staining and the serological test, though no sensitivity or specificity data were reported. 5 We determined the sensitivity and specificity of PLA2R1 tissue staining for detecting primary membranous glomerulopathy in a large renal biopsy series. This is the largest series to date examining PLA2R1 involvement in membranous glomerulopathy.…”

Glomerular Diseases

“…However, a large number of other infections and diseases may also be associated with MN (6). An accurate clinical history and a serologic inquiry using specific biomarkers (hepatitis B surface antigen, hepatitis C antibody, anti-DNA antibody, hypocomplementemia) can often uncover an underlying cause for MN; however, in the modern era, the detection of circulating antibodies against PLA2R1, using any one of a number of available assays, can also greatly aid in determining whether MN is idiopathic or secondary (7). These antibodies can be seen in 70%-80% of patients with idiopathic MN, whereas they are seldom detectable in secondary MN (7,8).…”

A case of gefitinib-associated membranous nephropathy in treatment for pulmonary adenocarcinoma

“…Recently, membranous type of PLA2R has been identified as an endogenous antigen existing in the glomerular epithelial cells and has gained attention as an etiology of idiopathic MGN [8]. A recent study demonstrates enhanced staining of PLA2R in glomeruli in cases with idiopathic MGN compared with negative staining in secondary MGN [9]. On the other hand, secondary MGN accounts for about 10-20 % of MGN, and causative antigens reported were drugs, tumor associated antigens such as CEA and cytokeratin 19 fragment, Hepatitis B virus, envelope antigen, and the other antigens in autoimmune diseases [6,7].…”