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

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. Electronic supplementary materialThe online version of this article (doi:10.1007/s10157-016-1235-2) contains supplementary material, which is available to authorized users.

Clinicopathological features of atypical membranous nephropathy with unknown etiology in adult Chinese patients

“…[ 7 ] In recent years, some scholars identified reactive epitopes in the CysR, CTLD1, and CTLD7 domains and confirmed the reactivity with soluble forms of each domain: CysR is a major antigen epitope of PLA2R antibodies, but the antigen epitope gradually spreading to CysRCTLD1 and CysRCTLD1CTLD7 with the progress of the disease, and the latter 2 were more closely with the activity of disease. [ 24 ] At present various studies reported serum PLA2R antibodies positive rate of iMN patients ranging from 48% to 82.3%, [ 25 – 29 ] in which the lowest positive rate (48%) was from Japan, [ 25 ] similar with our study, this phenomenon may have something to do with race and geographic environment. Some scholars pointed out that serum anti PLA2R antibodies even exist in SMN, and the positive rate ranging from 58.8% to 72.3%.…”

Development of a Standardized Chemiluminescence Immunoassay for the Detection of Autoantibodies Against Human M-Type Phospholipase A2 Receptor in Primary Membranous Nephropathy

“…The clinical sensitivity of the ChLIA exceeded that of ELISA and RC-IFA by 10.4% and 0.7%, respectively, at similar specificities (>99%). The anti-PLA2R-positive rates detected by ChLIA (83.9%), ELISA (73.5%), and RC-IFA (83.2%) were equal to or higher than the prevalence data determined among non-preselected patients with pMN by different methods, such as Western blot (53.0%-81.7%), 10,11 RC-IFA (48.0-82.3%), 12,13 ELISA (50.0-71.8%), 14,15 addressable laser bead immunoassay (51.5-66.9%), 16,17 luciferase immunoprecipitation systems assay (53.3%), 18 and time-resolved fluoroimmunoassay (71.0-89.7%). 19,20 These variations may be due to differences in assay techniques (e.g., epitope exposure, cutoff values, detected Ig subclass) and cohort characteristics (e.g., ethnicity, immunosuppressive treatment).…”

Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management

“…Antibodies against cytoplasmic alpha-enolase have long been known to be present in the serum of patients with primary and secondary MN (nearly 70%) [ 142 ] but never within the subepithelial deposits [ 143 ]. Antibodies against other cytoplasmic podocyte proteins, including aldose reductase and manganese superoxide dismutase 2, have also been detected in the serum and tissue eluates of microdissected glomeruli in biopsy samples from patients with MN [ 144 ].…”