Circulating antibodies to α-enolase and phospholipase A(2) receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy

BACKGROUND: Phospholipase A(2) receptor (PLA(2)R) 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. METHODS: We evaluated circulating antibodies to α-enolase by a dot blotting system and PLA(2)R 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. RESULTS: In 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-PLA(2)R antibody, whereas all patients with secondary MN were negative. Eight of the 12 PLA(2)R-positive patients (67 %) with primary MN also had anti α-enolase antibody. Although PLA(2)R 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. CONCLUSIONS: Circulating anti-α-enolase antibodies are highly present in both primary and secondary MN (about 70 %, respectively), while anti-PLA(2)R 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10157-016-1235-2) contains supplementary material, which is available to authorized users.