{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:03:07Z","timestamp":1792519387912,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006586","name":"Centre Hospitalier Universitaire de Nice","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Primary membranous nephropathy (pMN) is an autoimmune kidney disease and a common cause of nephrotic syndrome in adults. Rituximab is becoming a first line therapy for patients with persistent nephrotic syndrome with proven safety and efficacy, achieving remission in 60%\u201380% of cases. For the remaining 20%\u201340% of patients there is an urgent need to identify early biomarkers of resistance to rituximab to adapt therapeutic management. In nephrotic patients, rituximab is found in the blood more transiently than in other autoimmune diseases without proteinuria, due to rituximab wasting in the urine. However, rituximab immunomonitoring is not routinely performed. We evaluated the predictive value of serum rituximab levels in patients with pMN three months after rituximab injection (month-3) on clinical remission rates six months (month-6) and 12 months (month-12) after injection and investigated predictive factors for serum rituximab levels at month-3. Sixty-eight patients treated with rituximab between July 2015 and January 2020 from two French nephrology centers were included. We identified residual rituximab levels at month-3 as a novel early predictor of remission at month-6 (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&amp;lt;0.0001) and month-12 (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.001). Reduced likelihood of remission in patients with undetectable rituximab at month-3 was associated with lower serum albumin and higher anti-PLA2R1 titers at baseline and with lower serum albumin, higher proteinuria, higher CD19\n                    <jats:sup>+<\/jats:sup>\n                    counts and higher anti-PLA2R1 titers during follow-up. In multivariate analysis, high baseline proteinuria and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-6 and high baseline weight and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-12. We identified serum albumin at baseline as a predictive factor for serum rituximab levels at month-3. Patients with serum albumin below 22.5 g\/L at baseline had an 8.66-fold higher risk of having undetectable rituximab levels at month-3. Therefore, rituximab immunomonitoring in pMN patients treated with rituximab would allow the detection of patients at risk of treatment failure as early as month-3. Studies are needed to assess whether patients with low residual rituximab levels at month-3 may benefit from an early additional course of rituximab.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.738788","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T14:25:32Z","timestamp":1634135132000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy"],"prefix":"10.3389","volume":"12","author":[{"given":"Maxime","family":"Teisseyre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Cremoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Boyer-Suavet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Crepin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Benzaken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e9vin","family":"Zorzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Esnault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Brglez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Seitz-Polski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11761116","article-title":"Primary Membranous Nephropathy","volume":"12","author":"Couser","year":"2017","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","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":"B4","doi-asserted-by":"publisher","first-page":"1324804","DOI":"10.1155\/2019\/1324804","article-title":"Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation","volume":"2019","author":"Lateb","year":"2019","journal-title":"J Immunol Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.02.1033","article-title":"Complement Pathways in Membranous Nephropathy: Complex and Multifactorial","volume":"5","author":"Brglez","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1146\/annurev-pathol-020117-043811","article-title":"Molecular Pathogenesis of Membranous Nephropathy","volume":"15","author":"Ronco","year":"2019","journal-title":"Annu Rev Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85265","article-title":"Autoantibodies Against Thrombospondin Type 1 Domain-Containing 7A Induce Membranous Nephropathy","volume":"126","author":"Tomas","year":"2016","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.10.022","article-title":"A Novel Mouse Model of Phospholipase A2 Receptor 1-Associated Membranous Nephropathy Mimics Podocyte Injury in Patients","volume":"97","author":"Meyer-Schwesinger","year":"2020","journal-title":"Kidney Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0469","article-title":"In Vitro Mechanisms of Action of Rituximab on Primary Non-Hodgkin Lymphomas","volume":"101","author":"Manches","year":"2003","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210365","article-title":"Rituximab-Induced Inhibition of Antiapoptotic Cell Survival Pathways: Implications in Chemo\/Immunoresistance, Rituximab Unresponsiveness, Prognostic and Novel Therapeutic Interventions","volume":"26","author":"Bonavida","year":"2007","journal-title":"Oncogene"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-074716","article-title":"NK-Cell Activation and Antibody-Dependent Cellular Cytotoxicity Induced by Rituximab-Coated Target Cells Is Inhibited by the C3b Component of Complement","volume":"111","author":"Wang","year":"2008","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2008.001628","article-title":"Anti-CD20 Monoclonal Antibodies: Historical and Future Perspectives","volume":"95","author":"Lim","year":"2010","journal-title":"Haematologica"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11042-7","article-title":"Rituximab for Idiopathic Membranous Nephropathy","volume":"360","author":"Remuzzi","year":"2002","journal-title":"Lancet Lond Engl"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002628","article-title":"Rituximab Treatment of Idiopathic Membranous Nephropathy","volume":"73","author":"Fervenza","year":"2008","journal-title":"Kidney Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05080610","article-title":"Rituximab Therapy in Idiopathic Membranous Nephropathy: A 2-Year Study","volume":"5","author":"Fervenza","year":"2010","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B16","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":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.06.030","article-title":"Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy","volume":"5","author":"Sethi","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.02.433","article-title":"Successful Treatment of Patients With Refractory PLA2R-Associated Membranous Nephropathy With Obinutuzumab: A Report of 3 Cases","volume":"76","author":"Klomjit","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1159\/000501858","article-title":"Accelerating the Depletion of Circulating Anti-Phospholipase A2 Receptor Antibodies in Patients With Severe Membranous Nephropathy: Preliminary Findings With Double Filtration Plasmapheresis and Ofatumumab","volume":"144","author":"Podest\u00e0","year":"2020","journal-title":"Nephron"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.01.022","article-title":"Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy","volume":"6","author":"Teisseyre","year":"2021","journal-title":"Kidney Int Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfz041","article-title":"Rituximab Bioavailability in Primary Membranous Nephropathy","volume":"34","author":"Boyer-Suavet","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2017.09.001","article-title":"Detection and Quantification of Rituximab in the Human Urine","volume":"451","author":"Jacobs","year":"2017","journal-title":"J Immunol Methods"},{"key":"B23","first-page":"86","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis","year":"2012"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.26008","article-title":"Lessons for the Clinic From Rituximab Pharmacokinetics and Pharmacodynamics","volume":"5","author":"Golay","year":"2013","journal-title":"mAbs"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155","article-title":"FcRn: The Neonatal Fc Receptor Comes of Age","volume":"7","author":"Roopenian","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.3.5.16983","article-title":"Neonatal Fc Receptor and IgG-Based Therapeutics","volume":"3","author":"Kuo","year":"2011","journal-title":"mAbs"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-330357","article-title":"Fc Gamma Receptor IIb on Target B Cells Promotes Rituximab Internalization and Reduces Clinical Efficacy","volume":"118","author":"Lim","year":"2011","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/art.39167","article-title":"Internalization of Rituximab and the Efficiency of B Cell Depletion in Rheumatoid Arthritis and Systemic Lupus Erythematosus","volume":"67","author":"Reddy","year":"2015","journal-title":"Arthritis Rheumatol Hoboken Nj"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11791018","article-title":"High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy","volume":"14","author":"Seitz-Polski","year":"2019","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.08.045","article-title":"Retreatment With Rituximab for Membranous Nephropathy With Persistently Elevated Titers of Anti-Phospholipase A2 Receptor Antibody","volume":"95","author":"Dahan","year":"2019","journal-title":"Kidney Int"},{"key":"B31","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ekir.2016.05.002","article-title":"Membranous Nephropathy: Pilot Study of a Novel Regimen Combining Cyclosporine and Rituximab","volume":"1","author":"Waldman","year":"2016","journal-title":"Kidney Int Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.12.019","article-title":"Immunological Remission in PLA2R-Antibody-Associated Membranous Nephropathy: Cyclophosphamide versus Rituximab","volume":"93","author":"Van de Logt","year":"2018","journal-title":"Kidney Int"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07210810","article-title":"Anti-Phospholipase A2 Receptor Antibodies Correlate With Clinical Status in Idiopathic Membranous Nephropathy","volume":"6","author":"Hofstra","year":"2011","journal-title":"Clin J Am Soc Nephrol CJASN"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012030242","article-title":"Antiphospholipase A2 Receptor Antibody Titer and Subclass in Idiopathic Membranous Nephropathy","volume":"23","author":"Hofstra","year":"2012","journal-title":"J Am Soc Nephrol JASN"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfw121","article-title":"Anti-Phospholipase A2 Receptor Antibody Levels at Diagnosis Predicts Spontaneous Remission of Idiopathic Membranous Nephropathy","volume":"10","author":"Jullien","year":"2017","journal-title":"Clin Kidney J"},{"key":"B36","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 JASN"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111061","article-title":"Epitope Spreading of Autoantibody Response to PLA2R Associates With Poor Prognosis in Membranous Nephropathy","volume":"27","author":"Seitz-Polski","year":"2016","journal-title":"J Am Soc Nephrol JASN"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.738788\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T14:25:34Z","timestamp":1634135134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.738788\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,13]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2021.738788"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.738788","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,13]]},"article-number":"738788"}}