title: Circulating antibodies to α-enolase and phospholipase A2receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy.
abstract: BACKGROUND
  Phospholipase A2receptor (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.
  
  
  METHODS
  We 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.
  
  
  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-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.
  
  
  CONCLUSIONS
  Circulating 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.
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Miura
authors.affiliation: INSERM UMR_S 1155, UPMC Univ-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Tenon Hospital, Paris, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Internal Medicine, Kawana Hospital, Nagoya, Japan.
authors.forename: Harutaka
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Banno
authors.affiliation: INSERM UMR_S 1155, UPMC Univ-Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Tenon Hospital, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan. imaihiro@aichi-med-u.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Imai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007564:Japan; D007678:Kidney Glomerulus / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D010751:Phosphopyruvate Hydratase
keywords: Membranous nephropathy; Phospholipase A2 receptor; α-Enolase
references.citation: Am J Kidney Dis. 1994 Mar;23(3):358-64
references.pmid: 8128936
references.citation: J Am Soc Nephrol. 2010 Mar;21(3):507-19
references.pmid: 20150532
references.citation: Kidney Int. 2012 Oct;82(7):797-804
references.pmid: 22673885
references.citation: FEBS J. 2011 Apr;278(7):1064-74
references.pmid: 21261815
references.citation: Nat Rev Nephrol. 2012 Feb 28;8(4):203-13
references.pmid: 22371247
references.citation: J Rheumatol. 2006 Apr;33(4):695-7
references.pmid: 16583471
references.citation: Front Biosci. 2005 Jan 01;10:30-6
references.pmid: 15574344
references.citation: J Proteomics. 2011 Sep 6;74(10):2008-17
references.pmid: 21640210
references.citation: Clin Exp Immunol. 1984 Oct;58(1):57-62
references.pmid: 6383668
references.citation: N Engl J Med. 2014 Dec 11;371(24):2277-87
references.pmid: 25394321
references.citation: Eur J Immunol. 2000 Dec;30(12):3575-84
references.pmid: 11169399
references.citation: N Engl J Med. 2009 Jul 2;361(1):11-21
references.pmid: 19571279
references.citation: N Engl J Med. 2002 Jun 27;346(26):2053-60
references.pmid: 12087141
references.citation: Am J Kidney Dis. 2002 Apr;39(4):706-12
references.pmid: 11920335
references.citation: J Clin Immunol. 2007 Mar;27(2):181-92
references.pmid: 17235687
references.citation: J Am Soc Nephrol. 2011 Jun;22(6):1137-43
references.pmid: 21566055
references.citation: N Engl J Med. 2011 Feb 17;364(7):689-90
references.pmid: 21323563
references.citation: Clin Exp Immunol. 1999 Dec;118(3):445-50
references.pmid: 10594566
references.citation: Intern Med. 2007;46(17):1441-6
references.pmid: 17827846
references.citation: Autoimmun Rev. 2002 May;1(3):168-73
references.pmid: 12849011
references.citation: Am J Kidney Dis. 2010 Jul;56(1):157-67
references.pmid: 20378220
references.citation: J Neuroimmunol. 2005 May;162(1-2):130-6
references.pmid: 15833368
references.citation: Clin Exp Pharmacol Physiol. 2011 Jul;38(7):460-6
references.pmid: 21388432
references.citation: Arthritis Rheum. 2002 May;46(5):1196-201
references.pmid: 12115223
references.citation: Intern Med. 2002 Nov;41(11):936-42
references.pmid: 12487163
references.citation: Clin Immunol Immunopathol. 1996 Feb;78(2):120-9
references.pmid: 8625554
references.citation: Nephrol Dial Transplant. 2004 Mar;19(3):574-9
references.pmid: 14767011
references.citation: Clin Exp Nephrol. 2015 Aug;19(4):653-60
references.pmid: 25412738
references.citation: Autoimmun Rev. 2007 Jan;6(3):176-82
references.pmid: 17289554
references.citation: Cell Mol Life Sci. 2001 Jun;58(7):902-20
references.pmid: 11497239
references.citation: J Autoimmun. 1998 Dec;11(6):671-7
references.pmid: 9878089
references.citation: Lancet. 2004 Oct 2-8;364(9441):1252-9
references.pmid: 15464186
references.citation: N Engl J Med. 2011 Jun 2;364(22):2101-10
references.pmid: 21631322
references.citation: Clin J Am Soc Nephrol. 2012 Sep;7(9):1394-400
references.pmid: 22773590
references.citation: J Autoimmun. 1995 Dec;8(6):931-45
references.pmid: 8824716
references.citation: Pediatr Nephrol. 2010 Jun;25(6):1091-9
references.pmid: 20151159
references.citation: Proteomics. 2008 Mar;8(5):1000-8
references.pmid: 18240136
references.citation: Kidney Int. 1997 Jan;51(1):270-6
references.pmid: 8995742