{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:02:16Z","timestamp":1791666136527,"version":"4.3.4"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Rituximab is an established therapy for primary membranous nephropathy, but anti\u2212rituximab antibodies (ARA) have been associated with rituximab treatment failure. We report a 66\u2212year\u2212old woman with PLA2R\u2212positive membranous nephropathy who developed ARA positivity and clinical features consistent with rituximab treatment failure, including B\u2212cell reconstitution, undetectable serum rituximab levels, and worsening proteinuria despite declining anti\u2212PLA2R antibody titers. Kidney biopsy confirmed stage III membranous nephropathy. She was subsequently treated with the humanized type II anti\u2212CD20 antibody obinutuzumab, which induced complete depletion of circulating B cells, achieved therapeutic serum concentration, follow by both immunological and clinical remission within 8.5 months, despite persistent ARA positivity. This case suggests that obinutuzumab may be an effective rescue option after rituximab failure associated with ARA and underscores the importance of integrating therapeutic drug monitoring, ARA detection, and B\u2212cell kinetics assessment in the management of refractory membranous nephropathy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1758250","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:20Z","timestamp":1776059000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Obinutuzumab after anti-rituximab antibody-associated treatment failure in membranous nephropathy: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianying","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijun","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shenzhen Second People\u2019s Hospital, First Affiliated Hospital of Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-021-00303-z","article-title":"Membranous nephropathy","volume":"7","author":"Ronco","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.01.030","article-title":"Membranous nephropathy: a journey from bench to bedside","volume":"68","author":"Francis","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"B3","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":"B4","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.kint.2021.05.021","article-title":"Kdigo 2021 clinical practice guideline for the management of glomerular diseases","volume":"100","author":"Rovin","year":"2021","journal-title":"Kidney Int"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03069","article-title":"Neutralizing anti-rituximab antibodies and relapse in membranous nephropathy treated with rituximab","volume":"10","author":"Boyer-Suavet","year":"2019","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2025.04.059","article-title":"Anti-rituximab antibodies occurrence and clinical outcomes in patients with primary membranous nephropathy","volume":"10","author":"Allinovi","year":"2025","journal-title":"Kidney Int Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-225979","article-title":"Increasing the efficacy of Cd20 antibody therapy through the engineering of a new type ii anti-cd20 antibody with enhanced direct and immune effector cell-mediated b-cell cytotoxicity","volume":"115","author":"M\u00f6ssner","year":"2010","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2015.07.003","article-title":"Obinutuzumab in hematologic Malignancies: lessons learned to date","volume":"41","author":"Illidge","year":"2015","journal-title":"Cancer Treat Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.0000000000000555","article-title":"Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy","volume":"19","author":"Hu","year":"2024","journal-title":"Clin J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaf026","article-title":"Obinutuzumab is effective for the treatment of rituximab-refractory pla2r-associated membranous nephropathy","volume":"18","author":"Su","year":"2025","journal-title":"Clin\u00a0Kidney J"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.0000000000000152","article-title":"Risk factors associated with the occurrence of anti-rituximab antibodies in membranous nephropathy","volume":"18","author":"Teisseyre","year":"2023","journal-title":"Clin J Am Soc Nephrol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.IJMR_312_19","article-title":"Development of anti-rituximab antibodies in rituximab-treated patients: related parameters & consequences","volume":"155","author":"Saffari","year":"2022","journal-title":"Indian J Med Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.738788","article-title":"Rituximab immunomonitoring predicts remission in membranous nephropathy","volume":"12","author":"Teisseyre","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1024068","article-title":"Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-cd20 therapy alternatives","volume":"13","author":"Hartinger","year":"2022","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.859419","article-title":"Advances in the management of primary membranous nephropathy and rituximab-refractory membranous nephropathy","volume":"13","author":"Teisseyre","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.07.014","article-title":"The anti-pla2r antibody in membranous nephropathy: what we know and what remains a decade after its discovery","volume":"96","author":"van de Logt","year":"2019","journal-title":"Kidney Int"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2014070640","article-title":"Anti-phospholipase a2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy","volume":"26","author":"Ruggenenti","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.0000000000000237","article-title":"Anti-pla2r antibody levels and clinical risk factors for treatment nonresponse in membranous nephropathy","volume":"18","author":"Barbour","year":"2023","journal-title":"Clin J Am Soc Nephrol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1758250\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:21Z","timestamp":1776059001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1758250\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":18,"alternative-id":["10.3389\/fimmu.2026.1758250"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1758250","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1758250"}}