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- W2066709845 abstract "Membranous nephropathy (MN) is now regarded as an autoimmune kidney disease.1Makker S.P. Tramontano A. Idiopathic membranous nephropathy: an autoimmune disease.Semin Nephrol. 2011; 31: 333-340Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar The recent discovery of antipodocyte antibodies in human MN has opened a new line of thinking about this disease, but this finding still requires confirmation in large cohorts of patients with MN with sufficient follow-up. Until now, pathogenic insight has been derived from animal models2Heymann W. Hackel D.B. Harwood S. Wilson S.G. Hunter J.L. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions.Proc Soc Exp Biol Med. 1959; 100: 660-664Crossref PubMed Scopus (434) Google Scholar, 3Border W.A. Ward H.J. Kamil E.S. Cohen A.H. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen.J Clin Invest. 1982; 69: 451-461Crossref PubMed Scopus (207) Google Scholar, 4Kerjaschki D. Farquhar M.G. Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats.J Exp Med. 1983; 157: 667-686Crossref PubMed Scopus (377) Google Scholar, 5Kerjaschki D. Horvat R. Binder S. et al.Identification of a 400-kd protein in the brush borders of human kidney tubules that is similar to gp330, the nephritogenic antigen of rat Heymann nephritis.Am J Pathol. 1987; 129: 183-191PubMed Google Scholar, 6Saito A. Pietromonaco S. Loo A.K. Farquhar M.G. Complete cloning and sequencing of rat gp330/“megalin,” a distinctive member of the low density lipoprotein receptor gene family.Proc Natl Acad Sci U S A. 1994; 91: 9725-9729Crossref PubMed Scopus (501) Google Scholar, 7Farquhar M.G. Saito A. Kerjaschki D. Orlando R.A. The Heymann nephritis antigenic complex: megalin (gp330) and RAP.J Am Soc Nephrol. 1995; 6: 35-47PubMed Google Scholar and involved renal antigens (megalin is the prime example) not detectable in human kidneys, leaving the question about autoantigens in human MN unresolved.8Allegri L. Antigens in experimental models of membranous nephropathy: are they involved in human disease?.Nephrol Dial Transplant. 1997; 12: 1801-1804Crossref PubMed Scopus (9) Google Scholar New in vivo results9Murtas C. Bruschi M. Carnevali M.L. et al.In vivo characterization of renal auto-antigens involved in human auto-immune diseases: the case of membranous glomerulonephritis.Proteomics Clin Appl. 2011; 5: 90-97Crossref PubMed Scopus (17) Google Scholar show that podocyte antigens can be the target of autoimmunity in human MN; thus, circulating antipodocyte antibodies might become a biomarker of disease classification and/or activity.10Beck Jr, L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1598) Google Scholar, 11Prunotto M. Carnevali M.L. Candiano G. et al.Autoimmunity in membranous nephropathy targets aldose reductase and SOD2.J Am Soc Nephrol. 2010; 21: 507-519Crossref PubMed Scopus (187) Google Scholar, 12Bruschi M. Carnevali M.L. Murtas C. et al.Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens.J Proteomics. 2011; 74: 2008-2017Crossref PubMed Scopus (104) Google Scholar Further attempts to clarify this unexpected complexity are now required before new advances can be translated into clinical practice. Neutral endopeptidase (NEP)13Debiec H. Guigonis V. Mougenot B. et al.Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.N Engl J Med. 2002; 346: 2053-2060Crossref PubMed Scopus (436) Google Scholar and M-type phospholipase A2 receptor (PLA2R)10Beck Jr, L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1598) Google Scholar are 2 MN antigens that, in nonpathologic conditions, localize at the podocyte membrane. NEP was the first causative antigen identified in human MN, specifically in antenatal MN, an extremely rare form with abrupt onset at birth and spontaneous resolution.13Debiec H. Guigonis V. Mougenot B. et al.Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.N Engl J Med. 2002; 346: 2053-2060Crossref PubMed Scopus (436) Google Scholar, 14Debiec H. Nauta J. Coulet F. et al.Role of truncating mutations in MME gene in fetomaternal alloimmunisation and antenatal glomerulopathies.Lancet. 2004; 364: 1252-1259Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar These elegant studies showed that a podocyte antigen can be targeted by specific circulating antibodies, causing MN in humans. However, anti-NEP antibody levels in adults with MN have not been found to be different from apparently healthy controls,15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar suggesting that they are not involved in adult idiopathic MN. In this light, anti-NEP determination in patients seems without practical value. Anti-PLA2R antibodies have been implicated more recently in the pathogenesis of MN. They were discovered first by Beck et al10Beck Jr, L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1598) Google Scholar and later confirmed in a series of seminal articles10Beck Jr, L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1598) Google Scholar, 15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar, 16Beck Jr, L.H. Fervenza F.C. Beck D.M. et al.Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1543-1550Crossref PubMed Scopus (375) Google Scholar, 17Debiec H. Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy.N Engl J Med. 2011; 364: 689-690Crossref PubMed Scopus (251) Google Scholar, 18Hofstra J.M. Beck Jr, L.H. Beck D.M. Wetzels J.F. Salant D.J. Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2011; 6: 1286-1291Crossref PubMed Scopus (304) Google Scholar, 19Hofstra J.M. Debiec H. Short C.D. et al.Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1735-1743Crossref PubMed Scopus (255) Google Scholar, 20Hoxha E. Harendza S. Zahner G. et al.An immunofluorescence test for phospholipase-A(2)-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.Nephrol Dial Transplant. 2011; 26: 2526-2532Crossref PubMed Scopus (223) Google Scholar, 21Hoxha E. Kneissler U. Stege G. et al.Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.Kidney Int. 2012; 82: 797-804Crossref PubMed Scopus (230) Google Scholar, 22Michel P.A. Dahan K. Ancel P.Y. et al.Rituximab treatment for membranous nephropathy: a French clinical and serological retrospective study of 28 patients.Nephron Extra. 2011; 1: 251-261Crossref PubMed Google Scholar, 23Qin W. Beck Jr, L.H. Zeng C. et al.Anti-phospholipase A2 receptor antibody in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1137-1143Crossref PubMed Scopus (356) Google Scholar showing circulating anti-PLA2R immunoglobulin G4 (IgG4; the most common isotype) in 50%-70% of idiopathic MN cases. According to recent reports, there also is good concordance between serum positivity and glomerular PLA2R presence in immune deposits,17Debiec H. Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy.N Engl J Med. 2011; 364: 689-690Crossref PubMed Scopus (251) Google Scholar, 21Hoxha E. Kneissler U. Stege G. et al.Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.Kidney Int. 2012; 82: 797-804Crossref PubMed Scopus (230) Google Scholar at least during disease activity.24Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy [published online ahead of print December 6, 2012]. Nephrol Dial Transplant. doi:10.1093/ndt/gfs439.Google Scholar The more interesting feature of anti-PLA2R antibodies is their specificity for idiopathic MN.23Qin W. Beck Jr, L.H. Zeng C. et al.Anti-phospholipase A2 receptor antibody in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1137-1143Crossref PubMed Scopus (356) Google Scholar To our knowledge, only a few patients with clinical evidence of secondary MN have been found to have anti-PLA2R antibodies, whereas most have undetectable levels.20Hoxha E. Harendza S. Zahner G. et al.An immunofluorescence test for phospholipase-A(2)-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.Nephrol Dial Transplant. 2011; 26: 2526-2532Crossref PubMed Scopus (223) Google Scholar, 25Chakera A. Lasserson D. Beck Jr, L.H. Roberts I.S. Winearls C.G. Membranous nephropathy after use of UK-manufactured skin creams containing mercury.QJM. 2011; 104: 893-896Crossref PubMed Scopus (29) Google Scholar, 26Fervenza F.C. Downer G. Beck Jr, L.H. Sethi S. IgG4-related tubulointerstitial nephritis with membranous nephropathy.Am J Kidney Dis. 2011; 58: 320-324Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 27Gunnarsson I. Schlumberger W. Ronnelid J. Antibodies to M-type phospholipase A2 receptor (PLA2R) and membranous lupus nephritis.Am J Kidney Dis. 2012; 59: 585-586Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 28Knehtl M. Debiec H. Kamgang P. et al.A case of phospholipase A receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis.Am J Kidney Dis. 2011; 57: 140-143Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 29Svobodova B, Hruskova Z, Janatkova I, Jancova E, Tesar V. Measurement of anti-PLA2r antibodies in a Czech cohort of patients with membranous nephropathy. Poster presented at: 49th ERA-EDTA Congress; May 24-27, 2012; Paris, France.Google Scholar Therefore, data for anti-PLA2R specificity seem solid and their assessment may be extremely useful for clinicians, helping to differentiate between idiopathic and secondary forms of the disease. Correlation of anti-PLA2R antibody levels with disease activity has been investigated in a variety of cohorts. Findings are not homogeneous and probably are influenced by different criteria used for defining activity and remission. A publication from an Italian cohort15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar and other reports10Beck Jr, L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1598) Google Scholar, 21Hoxha E. Kneissler U. Stege G. et al.Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.Kidney Int. 2012; 82: 797-804Crossref PubMed Scopus (230) Google Scholar, 24Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy [published online ahead of print December 6, 2012]. Nephrol Dial Transplant. doi:10.1093/ndt/gfs439.Google Scholar assessed anti-PLA2R serum levels during disease activity in more than 400 patients and did not find an association with proteinuria. However, Hofstra et al found a correlation of anti-PLA2R with proteinuria in a small case series18Hofstra J.M. Beck Jr, L.H. Beck D.M. Wetzels J.F. Salant D.J. Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2011; 6: 1286-1291Crossref PubMed Scopus (304) Google Scholar and recently confirmed this finding in a larger population.19Hofstra J.M. Debiec H. Short C.D. et al.Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1735-1743Crossref PubMed Scopus (255) Google Scholar In this more extensive series, the correlation between anti-PLA2R level and proteinuria became statistically significant only after correction for IgG fractional clearance.19Hofstra J.M. Debiec H. Short C.D. et al.Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1735-1743Crossref PubMed Scopus (255) Google Scholar Because urinary excretion of anti-PLA2R IgG4 is increased during the acute phase of MN (G.M.G., unpublished observations, 2012), IgG fractional clearance may simply reflect increased excretion of these antibodies. A second aspect related to the prediction of distinct clinical outcomes is the significance of anti-PLA2R clearance after spontaneous or drug-induced remission. Longitudinal data are available for a limited number of patients with MN. Overall, about 60 patients have been tested for anti-PLA2R serum levels before and after treatment.16Beck Jr, L.H. Fervenza F.C. Beck D.M. et al.Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1543-1550Crossref PubMed Scopus (375) Google Scholar, 18Hofstra J.M. Beck Jr, L.H. Beck D.M. Wetzels J.F. Salant D.J. Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2011; 6: 1286-1291Crossref PubMed Scopus (304) Google Scholar, 20Hoxha E. Harendza S. Zahner G. et al.An immunofluorescence test for phospholipase-A(2)-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.Nephrol Dial Transplant. 2011; 26: 2526-2532Crossref PubMed Scopus (223) Google Scholar, 22Michel P.A. Dahan K. Ancel P.Y. et al.Rituximab treatment for membranous nephropathy: a French clinical and serological retrospective study of 28 patients.Nephron Extra. 2011; 1: 251-261Crossref PubMed Google Scholar These case series confirm the existence of a substantial number of outliers, consisting mainly of patients with low antibody levels at the same time as persistent proteinuria.16Beck Jr, L.H. Fervenza F.C. Beck D.M. et al.Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1543-1550Crossref PubMed Scopus (375) Google Scholar, 19Hofstra J.M. Debiec H. Short C.D. et al.Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1735-1743Crossref PubMed Scopus (255) Google Scholar The same discrepancy exists between disease activity and PLA2R expression in glomeruli, as evident in a recent article by Svobodova et al24Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H. Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy [published online ahead of print December 6, 2012]. Nephrol Dial Transplant. doi:10.1093/ndt/gfs439.Google Scholar showing that 60% of biopsy specimens still demonstrated PLA2R at the time of remission. A third and perhaps most important open issue with anti-PLA2R concerns patients with idiopathic MN but who have undetectable anti-PLA2R antibodies. This represents 20%-30% of patents with suspected idiopathic MN. In a series of reports, this group of patients presented and responded to therapy similarly to anti-PLA2R antibody–positive patients, calling into question the hypothesis of their being classified in the “inactive” phase of the disease.30Couser W.G. Basic and translational concepts of immune-mediated glomerular diseases.J Am Soc Nephrol. 2012; 23: 381-399Crossref PubMed Scopus (152) Google Scholar, 31Herrmann S.M. Sethi S. Fervenza F.C. Membranous nephropathy: the start of a paradigm shift.Curr Opin Nephrol Hypertens. 2012; 21: 203-210Crossref PubMed Scopus (22) Google Scholar Proteins normally expressed in the podocyte cytoplasm or mitochondria may become targets of autoimmunity in patients with MN. Studies performed by our group showed that 3 proteins, aldose reductase (AR),11Prunotto M. Carnevali M.L. Candiano G. et al.Autoimmunity in membranous nephropathy targets aldose reductase and SOD2.J Am Soc Nephrol. 2010; 21: 507-519Crossref PubMed Scopus (187) Google Scholar superoxide dismutase 2 (SOD2),11Prunotto M. Carnevali M.L. Candiano G. et al.Autoimmunity in membranous nephropathy targets aldose reductase and SOD2.J Am Soc Nephrol. 2010; 21: 507-519Crossref PubMed Scopus (187) Google Scholar and α-enolase,12Bruschi M. Carnevali M.L. Murtas C. et al.Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens.J Proteomics. 2011; 74: 2008-2017Crossref PubMed Scopus (104) Google Scholar fulfill the criteria for being classified as autoantigens in MN.32Murtas C. Ravani P. Ghiggeri G.M. New insights into membranous glomerulonephritis: from bench to bedside.Nephrol Dial Transplant. 2011; 26: 2428-2430Crossref PubMed Scopus (18) Google Scholar These proteins are expressed by human podocytes, and specific autoantibodies have been shown to colocalize with IgG4 and C5b-9 in immune deposits of MN biopsies. All these proteins are detectable at the surface of podocytes only in biopsy specimens from patients with MN, suggesting that it is their aberrant localization to the cell surface that makes it possible for them to be targeted by autoantibodies in disease states. In vitro experiments implicate oxidant triggers in this process. In a previously published cohort of 186 patients with MN evaluated at the time of diagnosis,15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar high serum levels of IgG4 antibodies were identified in a significant subset of patients (anti-AR in 34%, anti-SOD2 in 28%, and anti–α-enolase in 43%). Specificity was examined by testing for these autoantibodies in other nephropathies (IgA nephropathy and focal segmental glomerulosclerosis always gave negative results), although cases of secondary MN were not investigated. With respect to anti–α-enolase autoantibodies, elevated circulating IgG1 and IgG3 levels have been described in different autoimmune diseases,33Moodie F.D. Leaker B. Cambridge G. Totty N.F. Segal A.W. Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis.Kidney Int. 1993; 43: 675-681Crossref PubMed Scopus (87) Google Scholar, 34Migliorini P. Pratesi F. Bongiorni F. Moscato S. Scavuzzo M. Bombardieri S. The targets of nephritogenic antibodies in systemic autoimmune disorders.Autoimmun Rev. 2002; 1: 168-173Crossref PubMed Scopus (39) Google Scholar, 35Sabbatini A. Dolcher M.P. Marchini B. et al.Alpha-enolase is a renal-specific antigen associated with kidney involvement in mixed cryoglobulinemia.Clin Exp Rheumatol. 1997; 15: 655-658PubMed Google Scholar, 36Wakui H. Imai H. Komatsuda A. Miura A.B. Circulating antibodies against alpha-enolase in patients with primary membranous nephropathy (MN).Clin Exp Immunol. 1999; 118: 445-450Crossref PubMed Scopus (65) Google Scholar, 37Terrier B. Degand N. Guilpain P. Servettaz A. Guillevin L. Mouthon L. Alpha-enolase: a target of antibodies in infectious and autoimmune diseases.Autoimmun Rev. 2007; 6: 176-182Crossref PubMed Scopus (136) Google Scholar raising the possibility that this protein represents a nonspecific target in various conditions. However, we recently found no circulating IgG4 anti–α-enolase in a large cohort with lupus nephritis classes III, IV, and V (G.M.G., unpublished observations, 2012), which might suggest an IgG4 “isotype specificity” in idiopathic MN. Further data for anticytoplasmic antigen antibodies in other secondary forms of MN are needed; nevertheless, a possible lack of specificity may not exclude a role for these antigens in disease progression and/or histologic pattern definition. It is important to emphasize that the presence of other antibodies does not negate the functional relevance of anti-PLA2R; rather, analysis of a full panel of relevant autoantibodies in MN potentially could fill in some unclear aspects about anti-PLA2R outliers. MN autoantibodies coexist in different patients.15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar More than 50% of patients with MN in the Italian study group mentioned previously presented with at least 2 circulating antibodies; only 37 patients had completely negative results for all tested autoantibodies, representing 20% of the entire population. These autoantibody-negative patients may have autoantibodies that are still unidentified.12Bruschi M. Carnevali M.L. Murtas C. et al.Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens.J Proteomics. 2011; 74: 2008-2017Crossref PubMed Scopus (104) Google Scholar Another possibility is that they may represent the group of patients with truly inactive disease (eg, “immunologic remission”) that spontaneously evolves into clinical remission.31Herrmann S.M. Sethi S. Fervenza F.C. Membranous nephropathy: the start of a paradigm shift.Curr Opin Nephrol Hypertens. 2012; 21: 203-210Crossref PubMed Scopus (22) Google Scholar Results from the largest clinical study published to date15Murtas C. Bruschi M. Candiano G. et al.Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy.Clin J Am Soc Nephrol. 2012; 7: 1394-1400Crossref PubMed Scopus (122) Google Scholar indicated that the only subpopulation with better prognosis after 1 year (lower proteinuria and highest probability of complete remission) was defined by complete baseline autoantibody negativity. This finding might indirectly confirm a role for all antibodies in disease progression, rather than a single antibody predominating. Another area of interest is the monitoring of antibody levels longitudinally with clinical outcome after therapy. These data are available for anti-PLA2R in a limited number of patients with MN. Overall, about 60 patients have been tested for anti-PLA2R serum levels before and after treatment,16Beck Jr, L.H. Fervenza F.C. Beck D.M. et al.Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1543-1550Crossref PubMed Scopus (375) Google Scholar, 18Hofstra J.M. Beck Jr, L.H. Beck D.M. Wetzels J.F. Salant D.J. Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2011; 6: 1286-1291Crossref PubMed Scopus (304) Google Scholar, 20Hoxha E. Harendza S. Zahner G. et al.An immunofluorescence test for phospholipase-A(2)-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.Nephrol Dial Transplant. 2011; 26: 2526-2532Crossref PubMed Scopus (223) Google Scholar, 22Michel P.A. Dahan K. Ancel P.Y. et al.Rituximab treatment for membranous nephropathy: a French clinical and serological retrospective study of 28 patients.Nephron Extra. 2011; 1: 251-261Crossref PubMed Google Scholar confirming the existence of a group of patients with low antibody levels at the same time as persistent proteinuria.16Beck Jr, L.H. Fervenza F.C. Beck D.M. et al.Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.J Am Soc Nephrol. 2011; 22: 1543-1550Crossref PubMed Scopus (375) Google Scholar Again, extending the evaluation to the whole autoimmunity panel might offer additional insights. We recently completed a longitudinal analysis of 22 patients with MN, with repeated serum and urinary tests for the whole panel of new antipodocyte antibodies. The most interesting finding is that all individuals positive for anti-AR or anti-SOD2 antibodies after therapy failed to reach complete remission, whereas 50% of nonresponders or partial responders were anti-AR and/or anti-SOD2 positive (Fig 1). Other antibodies showed less consistent trends (G.M.G., unpublished observations, 2012). Caution is needed when interpreting these data, and further research is necessary. However, assessing the entire panel seems to offer the best information, likely overcoming the limitations of anti-PLA2R monitoring alone. It therefore is desirable that as many patients with idiopathic MN as possible be included in prospective studies designed to test all circulating antipodocyte antibodies with regard to distinct clinical outcome. Newly described autoantibodies may be promising MN biomarkers. Support: Istituto Giannina Gaslini provided logistic and financial support. This report was also supported by the Italian Ministry of Health “Ricerca Corrente” and contributions derived from “Cinque per mille dell'IRPEF.” We also acknowledge contributions from Renal Child Foundation and Fondazione La Nuova Speranza (“Progetto integrato per la definizione dei meccanismi implicati nella glomerulo sclerosi focale”). Financial Disclosure: The authors declare that they have no relevant financial interests. Circulating Antipodocyte Antibodies in Membranous Nephropathy: Pathophysiologic and Clinical RelevanceAmerican Journal of Kidney DiseasesVol. 62Issue 1PreviewMembranous nephropathy (MN), a major cause of glomerular disease and nephrotic syndrome in adults, is characterized by subepithelial deposits of immunoglobulin G (IgG) and complement activation, which leads to podocyte damage and proteinuria.1 Primary MN is associated with prominent deposition of IgG4 and variable amounts of IgG1, whereas secondary MN demonstrates primarily IgG1, IgG2, and IgG3. Diagnosis typically has depended on kidney biopsy, and proteinuria and serum creatinine values were the only criteria used to monitor patients and determine their need for treatment. Full-Text PDF" @default.
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- W2066709845 title "Circulating Antipodocyte Antibodies in Membranous Nephropathy: New Findings" @default.
- W2066709845 cites W1967633005 @default.
- W2066709845 cites W1970092281 @default.
- W2066709845 cites W1976941367 @default.
- W2066709845 cites W1986167294 @default.
- W2066709845 cites W1994157305 @default.
- W2066709845 cites W2001027510 @default.
- W2066709845 cites W2007098959 @default.
- W2066709845 cites W2014538635 @default.
- W2066709845 cites W2029198423 @default.
- W2066709845 cites W2030767711 @default.
- W2066709845 cites W2034094016 @default.
- W2066709845 cites W2037686491 @default.
- W2066709845 cites W2045220097 @default.
- W2066709845 cites W2054631505 @default.
- W2066709845 cites W2069809071 @default.
- W2066709845 cites W2072893670 @default.
- W2066709845 cites W2085673399 @default.
- W2066709845 cites W2096367702 @default.
- W2066709845 cites W2100925706 @default.
- W2066709845 cites W2108715719 @default.
- W2066709845 cites W2112378652 @default.
- W2066709845 cites W2119961035 @default.
- W2066709845 cites W2124211877 @default.
- W2066709845 cites W2125503275 @default.
- W2066709845 cites W2128089274 @default.
- W2066709845 cites W2131351493 @default.
- W2066709845 cites W2133344401 @default.
- W2066709845 cites W2137821793 @default.
- W2066709845 cites W2138543166 @default.
- W2066709845 cites W2140538253 @default.
- W2066709845 cites W2142371904 @default.
- W2066709845 cites W2154852379 @default.
- W2066709845 cites W2160514120 @default.
- W2066709845 cites W2166822765 @default.
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