title: Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.
abstract: OBJECTIVE
  The discovery of different podocyte autoantibodies in membranous nephropathy (MN) raises questions about their pathogenetic and clinical meaning. This study sought to define antibody isotypes and correlations; to compare levels in MN, other glomerulonephritides, and controls; and to determine their association with clinical outcomes.
  
  
  METHODS
  Serum IgG(1), IgG(3), and IgG(4) against aldose reductase (AR), SOD2, and α-enolase (αENO) were measured at diagnosis in 186 consecutive MN patients, in 96 proteinuric controls (36 with FSGS, and 60 with IgA nephropathy), and in 92 healthy people recruited in four Italian nephrology units. Anti-phospholipase A2 receptor (PLA2r) and anti-neutral endopeptidase (NEP) IgG(4) were titrated in the same specimens. Association with 1-year follow-up clinical parameters was studied in 120 patients.
  
  
  RESULTS
  IgG(4) was the most common isotype for all antibodies; IgG(1) and IgG(3) were nearly negligible. IgG(4) levels were positive in a significant proportion of MN patients (AR, 34%; SOD2, 28%; αENO, 43%). Antibody titers were higher in MN than in healthy and pathologic controls (P<0.005). Anti-NEP IgG(4) did not differ from normal controls (P=0.12). Anti-PLA2r IgG(4) was detected in 60% of patients and correlated with anti-AR, anti-SOD2, and anti-αENO IgG(4) (P<0.001). In MN patients negative for the whole antibody panel (20%), 1-year proteinuria was lower compared with patients with at least one antibody positivity (P<0.05).
  
  
  CONCLUSIONS
  Our data suggest that IgG(4) is the prevalent isotype for antibodies against cytoplasmic antigens of podocytes (AR, SOD2, αENO). Their levels were higher than in other proteinuric glomerulonephritides and in normal controls and were correlated with anti-PLA2r. Only baseline negativity for all known antibodies predicted lower 1-year proteinuria.
authors: Division of Nephrology, Dialysis, and Transplantation, Istituto Giannina Gaslini, Genoa, Italy.
authors: Corrado
authors: C
authors: Murtas
authors: Maurizio
authors: M
authors: Bruschi
authors: Giovanni
authors: G
authors: Candiano
authors: Gabriella
authors: G
authors: Moroni
authors: Riccardo
authors: R
authors: Magistroni
authors: Andrea
authors: A
authors: Magnano
authors: Francesca
authors: F
authors: Bruno
authors: Antonella
authors: A
authors: Radice
authors: Luciana
authors: L
authors: Furci
authors: Lucia
authors: L
authors: Argentiero
authors: Maria Luisa
authors: ML
authors: Carnevali
authors: Piergiorgio
authors: P
authors: Messa
authors: Francesco
authors: F
authors: Scolari
authors: Renato Alberto
authors: RA
authors: Sinico
authors: Loreto
authors: L
authors: Gesualdo
authors: Fernando C
authors: FC
authors: Fervenza
authors: Landino
authors: L
authors: Allegri
authors: Pietro
authors: P
authors: Ravani
authors: Gian Marco
authors: GM
authors: Ghiggeri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000276:immunology*; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007558:Italy; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000276:immunology; D050199:Podocytes / Q000201:enzymology / Q000276:immunology*; D011507:Proteinuria / Q000276:immunology; D054507:Receptors, Phospholipase A2 / Q000276:immunology; D012042:Registries; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000276:immunology; D013997:Time Factors; D055815:Young Adult; D000099156:Superoxide Dismutase 2
chemical_list: D000449:Aldehyde Reductase; D001323:Autoantibodies; D007074:Immunoglobulin G; D015260:Neprilysin; D010751:Phosphopyruvate Hydratase; D054507:Receptors, Phospholipase A2; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2