{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:51:38Z","timestamp":1791460298408,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06451"],"award-info":[{"award-number":["23K06451"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26K11171"],"award-info":[{"award-number":["26K11171"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Primary membranous nephropathy (MN) is classified into antigen\u2010defined subtypes, most commonly M\u2010type phospholipase A2 receptor (PLA2R)\u2010associated MN and neural epidermal growth factor\u2010like 1 (NELL1)\u2010associated MN. Whether complement activation differs between these subtypes remains unclear. This study compared their clinicopathological features and complement\u2010related protein expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively compared PLA2R\u2010associated MN (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917) and NELL1\u2010associated MN (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099), including five additional NELL1\u2010associated MN cases from an external institution. Glomerular C3 and C4d deposition were assessed by immunostaining, with quantitative C4d analysis using digital pathology. Complement\u2010related proteins were additionally evaluated by laser microdissection\u2013assisted data\u2010dependent acquisition mass spectrometry in cases with available proteomic data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with NELL1\u2010associated MN were older and showed greater interstitial fibrosis and tubular atrophy than those with PLA2R\u2010associated MN. Glomerular IgG4 and C3 deposition were significantly lower in NELL1\u2010associated MN. Quantitative analysis demonstrated lower glomerular C4d deposition in NELL1\u2010associated MN at both the glomerulus and patient levels, whereas C4d intensity was not significantly correlated with serum anti\u2010PLA2R antibody titres. In the proteomic analysis, C3, C5 and complement factor H were numerically more abundant in PLA2R\u2010associated MN than in NELL1\u2010associated MN, although these differences were not statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NELL1\u2010associated MN and PLA2R\u2010associated MN differ not only in clinical and histological features but also in glomerular complement deposition. Reduced C3 and C4d deposition in NELL1\u2010associated MN suggests less prominent glomerular complement activation than in PLA2R\u2010associated MN, supporting biological heterogeneity among antigen\u2010defined MN subtypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.70288","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:02:37Z","timestamp":1791457357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Complement Activation Profiles Between\n                    <scp>NELL1<\/scp>\n                    \u2010 and\n                    <scp>PLA2R<\/scp>\n                    \u2010Associated Membranous Nephropathy: A Clinicopathological and Proteomic Study"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-7814","authenticated-orcid":false,"given":"Taihei","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2474-8609","authenticated-orcid":false,"given":"Kang","family":"Dedong","sequence":"additional","affiliation":[{"name":"Department of Anatomy Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-3467","authenticated-orcid":false,"given":"Kunio","family":"Kawanishi","sequence":"additional","affiliation":[{"name":"Department of Anatomy Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7739-6648","authenticated-orcid":false,"given":"Masataka","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kajio","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6111-8027","authenticated-orcid":false,"given":"Nobuhiro","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-0464","authenticated-orcid":false,"given":"Mayumi","family":"Takahashi\u2010Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Institute of Medicine University of Tsukuba  Ibaraki Japan"},{"name":"Division of Cell Regulation, Center of Experimental Medicine and Systems Biology, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joichi","family":"Usui","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Institute of Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9566-184X","authenticated-orcid":false,"given":"Masaki","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Anatomy Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-8832","authenticated-orcid":false,"given":"Kazuho","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-3000","authenticated-orcid":false,"given":"Masayuki","family":"Iyoda","sequence":"additional","affiliation":[{"name":"Department of Nephrology Showa Medical University Graduate School of Medicine  Tokyo Japan"},{"name":"Department of Microbiology and Immunology Showa Medical University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1053\/j.ajkd.2025.08.013","article-title":"What's New in Membranous Nephropathy and How to Incorporate New Antigen Discoveries Into Clinical Practice: A Review","volume":"87","author":"Zand L.","year":"2026","journal-title":"American Journal of Kidney 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N.","year":"2021","journal-title":"Kidney International"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","DOI":"10.1186\/1746-1596-7-109","article-title":"The Continual Presence of C3d but Not IgG Glomerular Capillary Deposition in Stage I Idiopathic Membranous Nephropathy in Patients Receiving Corticosteroid Treatment","volume":"7","author":"Zhang R.","year":"2012","journal-title":"Diagnostic Pathology"},{"issue":"6","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.semnephrol.2013.08.004","article-title":"The Role of Complement in Membranous Nephropathy","volume":"33","author":"Ma H.","year":"2013","journal-title":"Seminars in Nephrology"},{"issue":"3","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.kint.2023.10.035","article-title":"Complement Activation and Effector Pathways in Membranous Nephropathy","volume":"105","author":"Kistler A. 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B.","year":"2016","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.3389\/fimmu.2018.01433","article-title":"Alternative Pathway Is Essential for Glomerular Complement Activation and Proteinuria in a Mouse Model of Membranous Nephropathy","volume":"9","author":"Luo W.","year":"2018","journal-title":"Frontiers in Immunology"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.70288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nep.70288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.70288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:02:41Z","timestamp":1791457361000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.70288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/nep.70288"],"URL":"https:\/\/doi.org\/10.1111\/nep.70288","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"value":"1320-5358","type":"print"},{"value":"1440-1797","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70288"}}