Circulating antibodies to \u03b1-enolase and phospholipase A2 receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy

Yukihiro Kimura,Hiroyuki Morita,Pierre Ronco,Hanna Debiec,Naoto Miura,Hirokazu Imai,Shogo Banno,Harutaka Yamada

doi:10.1007/s10157-016-1235-2

Abstract

BackgroundPhospholipase A2 receptor (PLA2R) is recognized as a target antigen in primary membranous nephropathy (MN); Anti-α-enolase antibody in primary and secondary MN has been proposed, however, little is known about the potential contribution of α-enolase to the pathogenesis of MN.MethodsWe evaluated circulating antibodies to α-enolase by a dot blotting system and PLA2R by indirect immunofluorescence, and glomerular deposition of these proteins in 25 patients with primary MN, 20 patients with secondary MN, 44 patients with collagen disease or severe infection, 60 patients with nephritis (each ten patients of IgA nephropathy, focal segmental gloemrulosclerosis, minimal change nephrotic syndrome, membranoproliferative glomeurlonephritis, diabetic glomerulosclerosis, and tubulointerstitial nephritis) as disease control, and 20 healthy subjects.ResultsIn primary MN, 18 of 25 sera (72 %) showed anti-α-enolase antibody (IgG1 and IgG4, 11 pts; IgG4 alone, six pts; IgG1 alone, one pt). In secondary MN, 15 of 20 sera (75 %) contained anti-α-enolase antibody (IgG1 and IgG3, 13 pts; IgG3 alone, two pts). No circulating anti-α-enolase antibody was found in 44 collagen diseases or septic patients, 60 nephritis without MN, and 20 healthy subjects. Twelve of 25 sera (48 %) from patients with primary MN were positive for anti-PLA2R antibody, whereas all patients with secondary MN were negative. Eight of the 12 PLA2R-positive patients (67 %) with primary MN also had anti α-enolase antibody. Although PLA2R antigen was present in a subepithelial pattern in 10 of 19 (52 %) patients with primary MN, α-enolase was never detected in glomerular deposits in 19 and ten patients with primary and secondary MN, respectively.ConclusionsCirculating anti-α-enolase antibodies are highly present in both primary and secondary MN (about 70 %, respectively), while anti-PLA2R antibodies are specific for primary MN (48 %) with a prevalence apparently lower in the Japanese population than in Chinese and Caucasian populations. The absence of α-enolase from subepithelial immune deposits suggests that anti-α-enolase antibodies do not contribute directly to immune-deposit formation, although they may have other pathogenic effects.

Highlights

Membranous nephropathy (MN)—a major glomerular disease and common cause of adult nephrotic syndrome— is characterized by glomerular subepithelial IgG deposits [1]
We evaluated circulating antibodies to a-enolase by a dot blotting system and phospholipase A2 receptor (PLA2R) by indirect immunofluorescence, and glomerular deposition of these proteins in 25 patients with primary MN, 20 patients with secondary MN, 44 patients with collagen disease or severe infection, 60 patients with nephritis as disease control, and 20 healthy subjects
We examined the effects of treatment on circulating anti- In paraffin-embedded kidney biopsy specimens, confocal bodies specific for a-enolase in a patient with primary MN, a microscopy showed the presence of PLA2R in subepithelial a-enolase was strongly expressed in tubular epithelium and was weak positive in glomerular parietal cells (Fig. 4d, e, f) and very weakly detected in the cytoplasm of glomerular cells on high magnification (Fig. 5b), but unlike PLA2R, a-enolase was never detected in subepithelial deposits in the 29 biopsy specimens where this was examined (Fig. 5b)

Summary

Introduction

Membranous nephropathy (MN)—a major glomerular disease and common cause of adult nephrotic syndrome— is characterized by glomerular subepithelial IgG deposits [1]. Beck et al demonstrated that IgG4 antibodies specific for M-type phospholipase A2 receptor (PLA2R) were present in glomerular eluates and serum from adult patients with primary MN [11]. Debiec et al reported that some patients who develop MN in early childhood had circulating anti-bovine serum albumin (BSA) antibodies and cationic BSA as a component of glomerular immune deposits [16]. A2 receptor (PLA2R) is recognized as a target antigen in primary membranous nephropathy (MN); Anti-a-enolase antibody in primary and secondary MN has been proposed, little is known about the potential contribution of a-enolase to the pathogenesis of MN

Methods

Results

Conclusion