{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:00:29Z","timestamp":1792555229417,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["414280945"],"award-info":[{"award-number":["414280945"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["264599542"],"award-info":[{"award-number":["264599542"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["iPRIME programme"],"award-info":[{"award-number":["iPRIME programme"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF19OC0056043"],"award-info":[{"award-number":["NNF19OC0056043"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Primary membranous nephropathy (MN) is caused by circulating autoantibodies binding to antigens on the podocyte surface. PLA\n                      <jats:sub>2<\/jats:sub>\n                      R1 is the main target antigen in 70%\u201380% of cases, but the pathogenesis is unresolved in 10%\u201315% of patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used native western blotting to identify IgG4 autoantibodies, which bind an antigen endogenously expressed on podocyte membranes, in the serum of the index patient with MN. These IgG4 autoantibodies were used to immunoprecipitate the target antigen, and mass spectrometry was used to identify Netrin G1 (NTNG1). Using native western blot and ELISA, NTNG1 autoantibodies were analyzed in cohorts of 888 patients with MN or other glomerular diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NTNG1 was identified as a novel target antigen in MN. It is a membrane protein expressed in healthy podocytes. Immunohistochemistry confirmed granular NTNG1 positivity in subepithelial glomerular immune deposits. In prospective and retrospective MN cohorts, we identified three patients with NTNG1-associated MN who showed IgG4-dominant circulating NTNG1 autoantibodies, enhanced NTNG1 expression in the kidney, and glomerular IgG4 deposits. No NTNG1 autoantibodies were identified in 561 PLA\n                      <jats:sub>2<\/jats:sub>\n                      R1 autoantibodies\u2013positive patients, 27 THSD7A autoantibodies\u2013positive patients, and 77 patients with other glomerular diseases. In two patients with available follow-up of 2 and 4 years, both NTNG1 autoantibodies and proteinuria persisted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NTNG1 expands the repertoire of target antigens in patients with MN. The clinical role of NTNG1 autoantibodies remains to be defined.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2022050608","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T15:10:18Z","timestamp":1660921818000},"page":"1823-1831","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":52,"title":["Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9786-9922","authenticated-orcid":false,"given":"Linda","family":"Reinhard","sequence":"first","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Machalitza","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-1474","authenticated-orcid":false,"given":"Thorsten","family":"Wiech","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Nephropathology Section, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann-Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Nephropathology Section, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"},{"name":"Institute of Pharmacology, Phillips University Marburg, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Lass\u00e9","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus M.","family":"Rinschen","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"},{"name":"Department of Biomedicine and Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Ferru","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-3067","authenticated-orcid":false,"given":"Jan Hinrich","family":"Br\u00e4sen","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Nephropathology Section, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Dr\u00f6mann","sequence":"additional","affiliation":[{"name":"Nierenzentrum und Dialyse L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Maria","family":"Rob","sequence":"additional","affiliation":[{"name":"Nierenzentrum und Dialyse L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-7709","authenticated-orcid":false,"given":"Sanjeev","family":"Sethi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elion","family":"Hoxha","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf A.K.","family":"Stahl","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,10]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/1744666X.2019.1548934","article-title":"Characterization of autoantibodies in primary membranous nephropathy and their clinical significance","volume":"15","author":"Stahl","year":"2019","journal-title":"Expert Rev Clin Immunol"},{"key":"B2-20250823","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1056\/NEJMoa012895","article-title":"Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies","volume":"346","author":"Debiec","year":"2002","journal-title":"N Engl J Med"},{"key":"B3-20250823","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa0810457","article-title":"M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy","volume":"361","author":"Beck","year":"2009","journal-title":"N Engl J Med"},{"key":"B4-20250823","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1056\/NEJMoa1409354","article-title":"Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy","volume":"371","author":"Tomas","year":"2014","journal-title":"N Engl J Med"},{"key":"B5-20250823","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.2018080852","article-title":"Exostosin 1\/exostosin 2-associated membranous nephropathy","volume":"30","author":"Sethi","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"B6-20250823","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.kint.2019.09.014","article-title":"Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy","volume":"97","author":"Sethi","year":"2020","journal-title":"Kidney Int"},{"key":"B7-20250823","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1681\/ASN.2020101395","article-title":"Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy","volume":"32","author":"Al-Rabadi","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"B8-20250823","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.kint.2020.05.030","article-title":"Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients","volume":"98","author":"Sethi","year":"2020","journal-title":"Kidney Int"},{"key":"B9-20250823","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1681\/ASN.2020081165","article-title":"Protocadherin 7-associated membranous nephropathy","volume":"32","author":"Sethi","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"B10-20250823","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.kint.2020.09.016","article-title":"Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis","volume":"100","author":"Caza","year":"2021","journal-title":"Kidney Int"},{"key":"B11-20250823","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.kint.2021.08.014","article-title":"Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy","volume":"100","author":"Le Quintrec","year":"2021","journal-title":"Kidney Int"},{"key":"B12-20250823","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.34067\/KID.0001492021","article-title":"Transforming growth factor beta receptor 3 (TGFBR3)-associated membranous nephropathy","volume":"2","author":"Caza","year":"2021","journal-title":"Kidney360"},{"key":"B13-20250823","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1681\/ASN.2021111488","article-title":"Hematopoietic stem cell transplant-membranous nephropathy is associated with protocadherin FAT1","volume":"33","author":"Sethi","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"B14-20250823","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.3389\/fimmu.2018.03035","article-title":"Antigen-specific IgG subclasses in primary and malignancy-associated membranous nephropathy","volume":"9","author":"von Haxthausen","year":"2018","journal-title":"Front Immunol"},{"key":"B15-20250823","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1056\/NEJMoa1013792","article-title":"Early-childhood membranous nephropathy due to cationic bovine serum albumin","volume":"364","author":"Debiec","year":"2011","journal-title":"N Engl J Med"},{"key":"B16-20250823","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cca.2013.03.015","article-title":"Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy","volume":"421","author":"D\u00e4hnrich","year":"2013","journal-title":"Clin Chim Acta"},{"key":"B17-20250823","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1681\/ASN.2019030273","article-title":"Clinical relevance of domain-specific phospholipase A2 receptor 1 antibody levels in patients with membranous nephropathy","volume":"31","author":"Reinhard","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"B18-20250823","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1681\/ASN.2016010050","article-title":"An indirect immunofluorescence method facilitates detection of thrombospondin type 1 domain-containing 7A-specific antibodies in membranous nephropathy","volume":"28","author":"Hoxha","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B19-20250823","doi-asserted-by":"crossref","first-page":"e0221293","DOI":"10.1371\/journal.pone.0221293","article-title":"Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy","volume":"14","author":"Mahmud","year":"2019","journal-title":"PLoS One"},{"key":"B20-20250823","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nprot.2006.62","article-title":"Blue native PAGE","volume":"1","author":"Wittig","year":"2006","journal-title":"Nat Protoc"},{"key":"B21-20250823","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1074\/mcp.O115.050229","article-title":"PRIDE Inspector Toolsuite: Moving toward a universal visualization tool for proteomics data standard formats and quality assessment of ProteomeXchange datasets","volume":"15","author":"Perez-Riverol","year":"2016","journal-title":"Mol Cell Proteomics"},{"issue":"D1","key":"B22-20250823","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Perez-Riverol","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"B23-20250823","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/s41379-019-0267-z","article-title":"Diagnostic role of renal biopsy in PLA2R1-antibody-positive patients with nephrotic syndrome","volume":"32","author":"Wiech","year":"2019","journal-title":"Mod Pathol"},{"key":"B24-20250823","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ygeno.2005.04.004","article-title":"Human netrin-G1 isoforms show evidence of differential expression","volume":"86","author":"Meerabux","year":"2005","journal-title":"Genomics"},{"key":"B26-20250823","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.1038\/emboj.2011.346","article-title":"Structural basis for cell surface patterning through NetrinG-NGL interactions","volume":"30","author":"Seiradake","year":"2011","journal-title":"EMBO J"},{"key":"B27-20250823","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.1523\/JNEUROSCI.20-17-06540.2000","article-title":"Netrin-G1: A novel glycosyl phosphatidylinositol-linked mammalian netrin that is functionally divergent from classical netrins","volume":"20","author":"Nakashiba","year":"2000","journal-title":"J Neurosci"},{"key":"B28-20250823","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/nn1148","article-title":"The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons","volume":"6","author":"Lin","year":"2003","journal-title":"Nat Neurosci"},{"key":"B29-20250823","doi-asserted-by":"crossref","first-page":"14801","DOI":"10.1073\/pnas.0706919104","article-title":"Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments","volume":"104","author":"Nishimura-Akiyoshi","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B30-20250823","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/nn1763","article-title":"NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation","volume":"9","author":"Kim","year":"2006","journal-title":"Nat Neurosci"},{"key":"B31-20250823","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/ajmg.a.31133","article-title":"NTNG1 mutations are a rare cause of Rett syndrome","volume":"140","author":"Archer","year":"2006","journal-title":"Am J Med Genet A"},{"key":"B32-20250823","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.pediatrneurol.2007.06.002","article-title":"Netrin G1 mutations are an uncommon cause of atypical Rett syndrome with or without epilepsy","volume":"37","author":"Nectoux","year":"2007","journal-title":"Pediatr Neurol"},{"key":"B33-20250823","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.biopsych.2004.11.022","article-title":"A family-based association study and gene expression analyses of netrin-G1 and -G2 genes in schizophrenia","volume":"57","author":"Aoki-Suzuki","year":"2005","journal-title":"Biol Psychiatry"},{"key":"B34-20250823","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3389\/fnmol.2019.00250","article-title":"NGL-1\/LRRC4C-mutant mice display hyperactivity and anxiolytic-like behavior associated with widespread suppression of neuronal activity","volume":"12","author":"Choi","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"B35-20250823","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3389\/fnmol.2019.00119","article-title":"NGL-1\/LRRC4C deletion moderately suppresses hippocampal excitatory synapse development and function in an input-independent manner","volume":"12","author":"Choi","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"B36-20250823","first-page":"1074","article-title":"Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy","volume":"372","author":"Meyer-Schwesinger","year":"2015","journal-title":"N Engl J Med"},{"key":"B37-20250823","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1523\/JNEUROSCI.1528-21.2021","article-title":"Robo2 drives target-selective peripheral nerve regeneration in response to glia-derived signals","volume":"42","author":"Murphy","year":"2022","journal-title":"J Neurosci"},{"key":"B38-20250823","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41573-021-00242-0","article-title":"The glomerular filtration barrier: A structural target for novel kidney therapies","volume":"20","author":"Daehn","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B39-20250823","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/1073858409355829","article-title":"The spine apparatus, synaptopodin, and dendritic spine plasticity","volume":"16","author":"Segal","year":"2010","journal-title":"Neuroscientist"},{"key":"B40-20250823","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fmed.2018.00221","article-title":"Proteinuric kidney diseases: A podocyte\u2019s slit diaphragm and cytoskeleton approach","volume":"5","author":"Yu","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B41-20250823","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1016\/j.ajpath.2011.01.017","article-title":"Ubiquitin C-terminal hydrolase-l1 activity induces polyubiquitin accumulation in podocytes and increases proteinuria in rat membranous nephropathy","volume":"178","author":"Meyer-Schwesinger","year":"2011","journal-title":"Am J Pathol"},{"key":"B42-20250823","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/cbf.3527","article-title":"Ubiquitin carboxy-terminal hydrolase L1: Physiology and pathology","volume":"38","author":"Matuszczak","year":"2020","journal-title":"Cell Biochem Funct"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2022050608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:49:10Z","timestamp":1786132150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2022050608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":41,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2022050608","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"2022-05-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-07","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}