{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:07:33Z","timestamp":1789506453446,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["1082317"],"award-info":[{"award-number":["1082317"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>Recent advances in membranous nephropathy treatment have focused on B cell depletion, which is incompletely effective, potentially due to persistent autoantibody-producing plasma cells or alternative pathways of injury. T cell costimulatory blockade [cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4)-Ig] to prevent T cell-dependent B cell activation and short-course proteasome inhibition (bortezomib) to deplete plasma cells may represent a complementary form of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lewis rats were immunized with Fx1A and complete Freund's adjuvant to induce experimental membranous nephropathy (Heymann nephritis or HN) and treated with CTLA4-Ig alone or CTLA4-Ig plus a short-course of bortezomib. Serum creatinine, proteinuria, kidney histology, serum anti-Fx1A levels, kidney and spleen messenger RNA expression, and flow cytometry on splenocytes were evaluated at 12 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats had significant and similar reductions in serum creatinine and proteinuria, with less histological kidney injury compared with untreated HN rats. Glomerular IgG deposition was reduced in CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats compared with untreated HN rats but there were no significant differences in serum anti-Fx1A levels. CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats exhibited significantly reduced T helper (Th)-17 cell cytokines (interleukin-6, -17, -21) and regulatory T cell (Foxp3, TGF-\u03b2) expression in the kidney but not the spleen. Immunohistochemical staining of CD4+ and intracellular STAT3+ cells was reduced in CTLA4-Ig plus bortezomib-treated and CTLA4-Ig-treated compared with untreated HN rats. On flow cytometry, CTLA4-Ig reduced B cells and plasma cells but not T cell subsets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CTLA4-Ig ameliorated induction of experimental membranous nephropathy, potentially through suppression of Th17 cells in the kidney, and may represent an effective adjunct treatment in membranous nephropathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf030","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T15:23:36Z","timestamp":1738855416000},"page":"2058-2073","source":"Crossref","is-referenced-by-count":6,"title":["T cell costimulatory blockade ameliorates induction of experimental membranous nephropathy potentially through T-helper 17 cell suppression in the kidney"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-2231","authenticated-orcid":false,"given":"Edmund Y M","family":"Chung","sequence":"first","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, The University of Sydney , Camperdown, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karli","family":"Shaw","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Ronning","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, The University of Sydney , Camperdown, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Yu Zhang","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hu","sequence":"additional","affiliation":[{"name":"Centre for Transplant and Renal Research, Westmead Institute for Medical Research , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Keung","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Prince of Wales Hospital , Randwick, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C H","family":"Harris","sequence":"additional","affiliation":[{"name":"Centre for Transplant and Renal Research, Westmead Institute for Medical Research , Westmead, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I","family":"Alexander","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research, Children's Hospital at Westmead , Westmead, NSW ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, The University of Sydney , Camperdown, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"2025102920015934000_bib1","doi-asserted-by":"publisher","first-page":"983","DOI":"10.2215\/CJN.11761116","article-title":"Primary membranous nephropathy","volume":"12","author":"Couser","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025102920015934000_bib2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1056\/NEJMoa1814427","article-title":"Rituximab or cyclosporine in the treatment of membranous nephropathy","volume":"381","author":"Fervenza","year":"2019","journal-title":"N Engl J Med"},{"key":"2025102920015934000_bib3","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1084\/jem.127.3.555","article-title":"Autologous immune complex nephritis induced with renal tubular antigen. 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