title: Reappraisal of PLA2R1 in membranous nephropathy: immunostaining method influence and association with IgG4-dominant phenotype.
abstract: The M-type phospholipase A2 receptor (PLA2R1) was identified recently as a specific target antigen in idiopathic membranous nephropathy. However, the influence of different sample preparation techniques on the immunostaining of PLA2R1 is unclear. Previous studies have identified IgG4 as the dominant subclass of PLA2R1 antibodies. However, it remains unclear whether the IgG subclass profiles of the glomerular immune complexes of PLA2R1-positive and -negative idiopathic membranous nephropathy cases are similar. To address these questions, we conducted the present study of 58 idiopathic membranous nephropathy cases. The PLA2R1 positivity rate for the paraffin-embedded sections was 61%, whereas that for the frozen sections was 65%. Nonspecific background staining was observed in the frozen sections. Discrepancies between different sample preparations occurred in three cases (6%); two cases were PLA2R1-positive in paraffin sections and PLA2R1-negative in frozen sections and one case was PLA2R1-negative in paraffin sections and PLA2R1-positive in frozen sections. Regarding the IgG subclass profile, 89% of the PLA2R1-positive cases demonstrated the IgG4-dominant/codominant phenotype versus 31% of the PLA2R1-negative cases (p < 0.001). Clinical characteristics and pathological findings did not significantly differ between PLA2R1-positive and -negative cases. In summary, the PLA2R1 immunofluorescence results were not affected by the different sample preparation techniques, although paraffin-embedded sections were preferred for the histological detection of PLA2R1 because of the nonspecific background staining observed in frozen sections. The observed lower frequency of the non-IgG4-dominant/codominant phenotype in PLA2R1-negative idiopathic membranous nephropathy cases may suggest that there are heterogeneous subgroups of this disease.
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan, shara@med.kobe-u.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Hara
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Goto
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kamiura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Naito
authors.forename: Naoko
authors.initials: N
authors.lastname: Imagawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
mesh_terms: D005260:Female; D005455:Fluorescent Antibody Technique; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054507:Receptors, Phospholipase A2 / Q000032:analysis*
chemical_list: D007074:Immunoglobulin G; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2
references.citation: Nephrol Dial Transplant. 2013 Jul;28(7):1839-44
references.pmid: 23223223
references.citation: Kidney Int. 2010 May;77(9):765-70
references.pmid: 20182413
references.citation: Kidney Int. 2012 Oct;82(7):797-804
references.pmid: 22673885
references.citation: Kidney Int. 2005 Jul;68(1):302-10
references.pmid: 15954921
references.citation: Clin Exp Immunol. 1984 Oct;58(1):57-62
references.pmid: 6383668
references.citation: Mod Pathol. 2013 Jun;26(6):799-805
references.pmid: 23328976
references.citation: J Am Soc Nephrol. 2013 Mar;24(4):677-83
references.pmid: 23431073
references.citation: Pediatr Nephrol. 2013 Dec;28(12):2307-11
references.pmid: 23903693
references.citation: Transplantation. 2013 May 27;95(10):1259-62
references.pmid: 23514961
references.citation: Am J Transplant. 2011 Oct;11(10):2144-52
references.pmid: 21827616
references.citation: Am J Nephrol. 2013;38(2):115-23
references.pmid: 23920047
references.citation: Mol Immunol. 2011 Aug;48(14):1656-65
references.pmid: 21757235
references.citation: N Engl J Med. 2009 Jul 2;361(1):11-21
references.pmid: 19571279
references.citation: J Am Soc Nephrol. 2014 Jun;25(6):1357-66
references.pmid: 24610926
references.citation: Semin Nephrol. 2013 Nov;33(6):531-42
references.pmid: 24161038
references.citation: Clin Chim Acta. 2013 Jun 5;421:213-8
references.pmid: 23541686
references.citation: PLoS One. 2013 Apr 26;8(4):e62151
references.pmid: 23637987
references.citation: J Am Soc Nephrol. 2011 Jun;22(6):1137-43
references.pmid: 21566055
references.citation: Nephrol Dial Transplant. 2007 Feb;22(2):568-76
references.pmid: 17164320
references.citation: Intern Med. 2002 Nov;41(11):936-42
references.pmid: 12487163
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: Hum Pathol. 2005 Nov;36(11):1178-85
references.pmid: 16260271
references.citation: Mod Pathol. 2013 May;26(5):709-15
references.pmid: 23196797
references.citation: Am J Transplant. 2008 Apr;8(4):753-60
references.pmid: 18294345
references.citation: J Am Soc Nephrol. 2013 Jul;24(8):1323-9
references.pmid: 23813219