TY - JOUR
T1 - Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy
AU - Murtas, Corrado
AU - Bruschi, Maurizio
AU - Candiano, Giovanni
AU - Moroni, Gabriella
AU - Magistroni, Riccardo
AU - Magnano, Andrea
AU - Bruno, Francesca
AU - Radice, Antonella
AU - Furci, Luciana
AU - Argentiero, Lucia
AU - Carnevali, Maria Luisa
AU - Messa, Piergiorgio
AU - Scolari, Francesco
AU - Sinico, Renato Alberto
AU - Gesualdo, Loreto
AU - Fervenza, Fernando C.
AU - Allegri, Landino
AU - Ravani, Pietro
AU - Ghiggeri, Gian Marco
PY - 2012/9/1
Y1 - 2012/9/1
N2 - Background and objectives 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. Design, setting, participants, & measurements Serum IgG1, IgG3, and IgG4 against aldose reductase (AR), SOD2, and α-enolase (αENO) were measured at diagnosis in 186 consecutiveMN 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) IgG4 were titrated in the same specimens. Association with 1-year follow-up clinical parameters was studied in 120 patients. Results IgG4 was the most common isotype for all antibodies; IgG1 and IgG3 were nearly negligible. IgG4 levels were positive in a significant proportion ofMNpatients (AR, 34%; SOD2, 28%; aENO, 43%).Antibody titerswere higher in MN than in healthy and pathologic controls (P<0.005). Anti-NEP IgG4 did not differ from normal controls (P=0.12). Anti-PLA2r IgG4 was detected in 60% of patients and correlated with anti-AR, anti-SOD2, and anti-αENO IgG4 (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 IgG4 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.
AB - Background and objectives 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. Design, setting, participants, & measurements Serum IgG1, IgG3, and IgG4 against aldose reductase (AR), SOD2, and α-enolase (αENO) were measured at diagnosis in 186 consecutiveMN 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) IgG4 were titrated in the same specimens. Association with 1-year follow-up clinical parameters was studied in 120 patients. Results IgG4 was the most common isotype for all antibodies; IgG1 and IgG3 were nearly negligible. IgG4 levels were positive in a significant proportion ofMNpatients (AR, 34%; SOD2, 28%; aENO, 43%).Antibody titerswere higher in MN than in healthy and pathologic controls (P<0.005). Anti-NEP IgG4 did not differ from normal controls (P=0.12). Anti-PLA2r IgG4 was detected in 60% of patients and correlated with anti-AR, anti-SOD2, and anti-αENO IgG4 (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 IgG4 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.
UR - http://www.scopus.com/inward/record.url?scp=84866119996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866119996&partnerID=8YFLogxK
U2 - 10.2215/CJN.02170312
DO - 10.2215/CJN.02170312
M3 - Article
C2 - 22773590
AN - SCOPUS:84866119996
SN - 1555-9041
VL - 7
SP - 1394
EP - 1400
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 9
ER -