{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:19:10Z","timestamp":1792513150568,"version":"4.5.0"},"reference-count":37,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP18ek0109354"],"award-info":[{"award-number":["JP18ek0109354"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Accounting for about 20 to 50% of cases of primary nephrotic syndrome, membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. A rat model created nearly 60 years ago to research the primary MN disorder, Heymann nephritis, has provided us with a plethora of important information. Recently, our knowledge about MN has dramatically progressed. Heymann nephritis and human MN are now known to share a high degree of similarity in pathogenesis. This review summarizes our current understanding of MN pathogenesis while focusing particularly on the immunological aspects.<\/ns4:p>","DOI":"10.12688\/f1000research.17589.1","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T05:00:07Z","timestamp":1558674007000},"page":"734","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Immunology of membranous nephropathy"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4313-2911","authenticated-orcid":false,"given":"Shin'ichi","family":"Akiyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enyu","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8858-632X","authenticated-orcid":false,"given":"Shoichi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"102-11","DOI":"10.1016\/j.jfma.2014.11.002","article-title":"Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment.","volume":"114","author":"W Lai","year":"2015","journal-title":"J Formos Med Assoc."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"150-8","DOI":"10.1681\/ASN.2013020185","article-title":"Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy.","volume":"25","author":"J van den Brand","year":"2014","journal-title":"J Am Soc Nephrol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"660-4","DOI":"10.3181\/00379727-100-24736","article-title":"Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions.","volume":"100","author":"W Heymann","year":"1959","journal-title":"Proc Soc Exp Biol Med."},{"key":"ref-4","first-page":"189-95","article-title":"Passive Heymann's nephritis as a model of immune glomerulonephritis mediated by antibodies to immunoglobulins.","volume":"41","author":"M Zanetti","year":"1980","journal-title":"Clin Exp Immunol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"5557-61","DOI":"10.1073\/pnas.79.18.5557","article-title":"The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border.","volume":"79","author":"D Kerjaschki","year":"1982","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"3060-6","DOI":"10.1681\/ASN.2007030342","article-title":"Intramolecular epitope spreading in Heymann nephritis.","volume":"18","author":"P Shah","year":"2007","journal-title":"J Am Soc Nephrol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"2053-60","DOI":"10.1056\/NEJMoa012895","article-title":"Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.","volume":"346","author":"H Debiec","year":"2002","journal-title":"N Engl J Med."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"S27-32","DOI":"10.1097\/01.ASN.0000067649.64849.75","article-title":"Antenatal membranous glomerulonephritis with vascular injury induced by anti-neutral endopeptidase antibodies: toward new concepts in the pathogenesis of glomerular diseases.","volume":"14 Suppl 1","author":"H Debiec","year":"2003","journal-title":"J Am Soc Nephrol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"2579-2589","DOI":"10.1681\/ASN.2017020178","article-title":"PLA2R and THSD7A: Disparate Paths to the Same Disease?","volume":"28","author":"L Beck","year":"2017","journal-title":"J Am Soc Nephrol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"11-21","DOI":"10.1056\/NEJMoa0810457","article-title":"M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.","volume":"361","author":"L Beck","year":"2009","journal-title":"N Engl J Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1286-91","DOI":"10.2215\/CJN.07210810","article-title":"Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy.","volume":"6","author":"J Hofstra","year":"2011","journal-title":"Clin J Am Soc Nephrol."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"e62151","DOI":"10.1371\/journal.pone.0062151","article-title":"Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy.","volume":"8","author":"Y Oh","year":"2013","journal-title":"PLoS One."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"257-61","DOI":"10.4103\/0971-4065.160334","article-title":"Prevalence of serum anti M-type phospholipase A2 receptor antibody in primary membranous nephropathy: A single center experience.","volume":"26","author":"N Gopalakrishnan","year":"2016","journal-title":"Indian J Nephrol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"5076-5083","DOI":"10.12659\/MSM.909815","article-title":"Clinical and Histological Features of Phospholipase A2 Receptor-Associated and Thrombospondin Type-I Domain-containing 7A-Associated Idiopathic Membranous Nephropathy: A Single Center Retrospective Study from China.","volume":"24","author":"D Zhang","year":"2018","journal-title":"Med Sci Monit."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"2277-2287","DOI":"10.1056\/NEJMoa1409354","article-title":"Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.","volume":"371","author":"N Tomas","year":"2014","journal-title":"N Engl J Med."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"1137-43","DOI":"10.1681\/ASN.2010090967","article-title":"Anti-phospholipase A2 receptor antibody in membranous nephropathy.","volume":"22","author":"W Qin","year":"2011","journal-title":"J Am Soc Nephrol."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"585-6","DOI":"10.1053\/j.ajkd.2011.10.044","article-title":"Antibodies to M-type phospholipase A2 receptor (PLA2R) and membranous lupus nephritis.","volume":"59","author":"I Gunnarsson","year":"2012","journal-title":"Am J Kidney Dis."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"302-13","DOI":"10.1681\/ASN.2014050502","article-title":"Identification of a major epitope recognized by PLA2R autoantibodies in primary membranous nephropathy.","volume":"26","author":"M Fresquet","year":"2015","journal-title":"J Am Soc Nephrol."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"56-68","DOI":"10.1016\/j.imlet.2014.11.001","article-title":"B cell epitope spreading: mechanisms and contribution to autoimmune diseases.","volume":"163","author":"C Cornaby","year":"2015","journal-title":"Immunol Lett."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1526-33","DOI":"10.1056\/NEJMoa021933","article-title":"Development of autoantibodies before the clinical onset of systemic lupus erythematosus.","volume":"349","author":"M Arbuckle","year":"2003","journal-title":"N Engl J Med."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"5326-32","DOI":"10.4049\/jimmunol.168.10.5326","article-title":"Immune responses to small nuclear ribonucleoproteins: antigen-dependent distinct B cell epitope spreading patterns in mice immunized with recombinant polypeptides of small nuclear ribonucleoproteins.","volume":"168","author":"U Deshmukh","year":"2002","journal-title":"J Immunol."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"8409-14","DOI":"10.4049\/jimmunol.175.12.8409","article-title":"Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjogren's syndrome.","volume":"175","author":"R Scofield","year":"2005","journal-title":"J Immunol."},{"key":"ref-23","doi-asserted-by":"publisher","DOI":"10.1371\/annotation\/2e462817-ab93-4d78-95a4-1d8b9d172971","article-title":"Correction: Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis.","volume":"7","author":"J Sokolove","year":"2012","journal-title":"PLoS One."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"166-71","DOI":"10.1023\/A:1020551610319","article-title":"Centrosome proteins: a major class of autoantigens in scleroderma.","volume":"19","author":"I Gavanescu","year":"1999","journal-title":"J Clin Immunol."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"5265-70","DOI":"10.4049\/jimmunol.166.8.5265","article-title":"Intermolecular antigen spreading occurs during the preclinical period of human type 1 diabetes.","volume":"166","author":"B Brooks-Worrell","year":"2001","journal-title":"J Immunol."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"138-147","DOI":"10.1053\/j.ajkd.2016.01.030","article-title":"Membranous Nephropathy: A Journey From Bench to Bedside.","volume":"68","author":"J Francis","year":"2016","journal-title":"Am J Kidney Dis."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"1517-33","DOI":"10.1681\/ASN.2014111061","article-title":"Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.","volume":"27","author":"B Seitz-Polski","year":"2016","journal-title":"J Am Soc Nephrol."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"3739-3746","DOI":"10.1681\/ASN.2016010093","article-title":"Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China.","volume":"27","author":"X Xu","year":"2016","journal-title":"J Am Soc Nephrol."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"1949-54","DOI":"10.1681\/ASN.2012060577","article-title":"Recurrent membranous nephropathy in an allograft caused by IgG3\u03ba targeting the PLA2 receptor.","volume":"23","author":"H Debiec","year":"2012","journal-title":"J Am Soc Nephrol."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"1096-107","DOI":"10.1172\/JCI112408","article-title":"Complement-induced glomerular epithelial cell injury. Role of the membrane attack complex in rat membranous nephropathy.","volume":"77","author":"A Cybulsky","year":"1986","journal-title":"J Clin Invest."},{"key":"ref-31","first-page":"121-8","article-title":"Membrane attack complex deposition in experimental glomerular injury.","volume":"120","author":"D Perkinson","year":"1985","journal-title":"Am J Pathol."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"1339-50","DOI":"10.1172\/JCI109987","article-title":"A new role for complement in experimental membranous nephropathy in rats.","volume":"66","author":"D Salant","year":"1980","journal-title":"J Clin Invest."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"30-42","DOI":"10.1159\/000481635","article-title":"Membranous Nephropathy: Approaches to Treatment.","volume":"47 Suppl 1","author":"A Bomback","year":"2018","journal-title":"Am J Nephrol."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"653-60","DOI":"10.1007\/s10157-014-1054-2","article-title":"Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy.","volume":"19","author":"S Akiyama","year":"2015","journal-title":"Clin Exp Nephrol."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"e0138841","DOI":"10.1371\/journal.pone.0138841","article-title":"Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy.","volume":"10","author":"T Iwakura","year":"2015","journal-title":"PLoS One."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"e0158154","DOI":"10.1371\/journal.pone.0158154","article-title":"Anti-Phospholipase A2 Receptor (PLA2R) Antibody and Glomerular PLA2R Expression in Japanese Patients with Membranous Nephropathy.","volume":"11","author":"K Hihara","year":"2016","journal-title":"PLoS One."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"832-840","DOI":"10.1093\/ndt\/gfx235","article-title":"Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy.","volume":"33","author":"N Hayashi","year":"2018","journal-title":"Nephrol Dial Transplant."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-734\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-734\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-734\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T05:05:09Z","timestamp":1558674309000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-734\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,24]]},"references-count":37,"URL":"https:\/\/doi.org\/10.12688\/f1000research.17589.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.19233.r48795","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.19233.r48793","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.19233.r48794","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,24]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-734\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.19233.r48794, Laurence Beck, Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA, 24 May 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-734\/v1#referee-response-48794","order":0,"name":"referee-response-48794","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.19233.r48793, David Salant, Department of Renal Section, Boston University Medical Center, Boston, 02118, USA, 24 May 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-734\/v1#referee-response-48793","order":1,"name":"referee-response-48793","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.19233.r48795, Hanna Debiec, Universit\u00e9 Pierre et Marie Curie, Sorbonne Universit\u00e9s, Paris, France, 24 May 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-734\/v1#referee-response-48795","order":2,"name":"referee-response-48795","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Japan Agency for Medical Research and Development [JP18ek0109354] and a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labour Sciences Research Grants [H29-nanchi(nan)-ippan-017] from the Ministry of Health, Labour and Welfare of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}