Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy

Abstract

The M-type phospholipase A2 receptor (PLA2R) is a target autoantigen in adult idiopathic membranous nephropathy (MN), but the prevalence of autoantibodies against PLA2R is unknown among Chinese patients with MN. Here, we measured anti-PLA2R antibody in the serum of 60 patients with idiopathic MN, 20 with lupus-associated MN, 16 with hepatitis B (HBV)-associated MN, and 10 with tumorassociated MN. Among patients with idiopathic MN, 49 (82%) had detectable anti-PLA2R autoantibodies using a Western blot assay; an assay with greater sensitivity detected very low titers of anti-PLA2R in 10 of the remaining 11 patients. Using the standard assay, we detected anti-PLA2R antibody in only 1 patient with lupus, 1 with HBV, and 3 with cancer, producing an overall specificity of 89% in this cohort limited to patients with secondary MN. The enhanced assay detected low titers of anti-PLA2R in only 2 additional samples of HBV-associated MN. In summary, these results suggest that PLA2R is a major target antigen in Chinese idiopathic MN and that detection of anti-PLA2R is a sensitive test for idiopathic MN.

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

“…If this is the case, the presence of an otherwise known secondary etiology in the setting of membranous glomerulopathy with positive PLA2R1 is by definition the chance occurrence of two diseases. 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.…”

“…IgG4-predominant staining is associated with primary membranous glomerulopathy, whereas IgG1, IgG2, and IgG3 predominate in the deposits of secondary membranous glomerulopathy. 3,[23][24][25][26] However, the sensitivity and specificity of various IgG subtype staining patterns for primary membranous glomerulopathy has not been well documented. We examined the IgG subtypes in cases of secondary membranous with positive PLA2R1 to determine whether they would follow the pattern of idiopathic membranous glomerulopathy with IgG4-predominant staining or that of secondary membranous glomerulopathy with IgG1 À 3 dominant staining.…”

“…The presence of PLA2R1 antibodies in the serum has been shown in previous reports to have a sensitivity of 70 À 82% and a specificity of 89 À 100%, for the detection of primary membranous glomerulopathy. 2,3 Despite the fact that PLA2R1 serological tests have been described in multiple reports, there are limited data available on the sensitivity and specificity of PLA2R1 staining in the renal tissue. Further, most of the reports to date of immunofluorescence testing for PLA2R1 in tissue use confocal microscopy that is not readily available in most pathology laboratories.…”

IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression

“…[2][3][4] However, other potential antigens in primary/idiopathic membranous glomerulonephritis may also evoke an IgG4 response. [5][6][7][8] Also, one has to consider that the presence of an underlying condition, that can be associated with membranous glomerulonephritis, does not necessarily exclude the possibility of a primary membranous glomerulonephritis, particularly if the glomerular capillary deposits are IgG4 dominant (eg, a person with a malignancy or hepatitis B or C virus infection can have membranous glomerulonephritis independent of these conditions).…”

“…2 These data were later confirmed by other studies. 3,4 However, PLA2R may not be the only target antigen in idiopathic membranous glomerulonephritis, because other recent studies described potential target antigens such as aldose reductase, superoxide dismutase, 5 aenolase 6 and bovine serum albumin, 7 however, with less prevalence. 8 Many patients with primary membranous glomerulonephritis have several types of circulating anti-podocyte antibodies at the same time but, among these antibodies, anti-PLA2R antibodies are the most prevalent.…”