{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:22:54Z","timestamp":1791422574524,"version":"4.3.3"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,8]]},"abstract":"\n Background and objectives<\/jats:title>\n Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2\u201325.0 years old) and age of onset of nephrotic syndrome 1\u201318 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid-dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg\/m\n 2<\/jats:sup>\n ) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was performed at baseline and regular intervals until relapse. Median follow-up duration postrituximab was 26.7 months (range =6.5\u201366.5 months). Baseline immunologic subsets were examined for association with rituximab response defined as resolution of proteinuria with discontinuation of prednisolone and CNI 3 months postrituximab.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Twelve patients (54.5%) responded to rituximab. Mitogen\u2013stimulated CD154\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n subset before rituximab was significantly lower in FSGS responders compared with nonresponders (54.9%\u00b128.1% versus 78.9%\u00b116.4%;\n P<\/jats:italic>\n =0.03). IFN-\n \u03b3<\/jats:italic>\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n and IL-2\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n were similarly decreased in responders compared with nonresponders (0.6%\u00b10.8% versus 7.5%\u00b16.1%;\n P<\/jats:italic>\n =0.003 and 0.2%\u00b10.5% versus 4.0%\u00b14.7%;\n P<\/jats:italic>\n <0.01, respectively). Recovery of all three activation subsets occurred 6 months postrituximab treatment (CD154\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n , 74.8%\u00b117.2%; IFN-\n \u03b3<\/jats:italic>\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n , 7.1%\u00b17.7%; and IL-2\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n , 7.9%\u00b110.9%;\n P<\/jats:italic>\n <0.01). Receiver\u2013operating characteristic analysis using optimal cutoff values showed that activated CD154\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n <83.3% (area under the curve [AUC], 0.81; 95% confidence interval [95% CI], 0.61 to 1.00), IFN-\n \u03b3<\/jats:italic>\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n <2.5% (AUC, 0.90; 95% CI, 0.75 to 1.00), and IL-2\n +<\/jats:sup>\n CD3\n +<\/jats:sup>\n <0.3% (AUC, 0.78; 95% CI, 0.57 to 0.98) were good predictors of rituximab response.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We have identified prognostic markers that define a subset of patients with FSGS bearing an immunologic signature representing hyporesponsiveness to T cell stimulation and therefore, who respond better to rituximab.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.11941115","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T22:48:57Z","timestamp":1465339737000},"page":"1360-1368","source":"Crossref","is-referenced-by-count":35,"title":["T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS"],"prefix":"10.2215","volume":"11","author":[{"given":"Chang-Yien","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Desheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes Paula","family":"Resontoc","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar-Hui","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiong-Huak","family":"Chan","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Medicine Dean's Office, National University of Singapore, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry Yew-Weng","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mya","family":"Than","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley C.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong-Peng","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wee-Song","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Kim","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine and"},{"name":"Department of Paediatric Medicine, Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,6,7]]},"reference":[{"issue":"Suppl 3","key":"B1-20230816","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/ndt\/14.suppl_3.68","article-title":"Clinical picture and outcome of primary focal segmental glomerulosclerosis.","volume":"14","author":"Korbet","year":"1999","journal-title":"Nephrol Dial Transplant"},{"key":"B2-20230816","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1097\/00008480-199504000-00011","article-title":"Focal segmental glomerulosclerosis in children.","volume":"7","author":"Ingulli","year":"1995","journal-title":"Curr Opin Pediatr"},{"key":"B3-20230816","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1007\/s00467-004-1434-z","article-title":"Change of the course of steroid-dependent nephrotic syndrome after rituximab 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Nephrol"},{"key":"B10-20230816","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.2215\/CJN.09421010","article-title":"Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: A randomized controlled trial.","volume":"6","author":"Ravani","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B11-20230816","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00467-011-1997-4","article-title":"Short-term efficacy of rituximab versus tacrolimus in steroid-dependent nephrotic syndrome.","volume":"27","author":"Sinha","year":"2012","journal-title":"Pediatr Nephrol"},{"key":"B12-20230816","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00467-009-1191-0","article-title":"Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children.","volume":"24","author":"Kamei","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"B13-20230816","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.5301\/jn.5000096","article-title":"Efficacy and safety of rituximab treatment in children with primary glomerulonephritis.","volume":"25","author":"Zachwieja","year":"2012","journal-title":"J Nephrol"},{"key":"B14-20230816","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00467-011-1778-0","article-title":"Rituximab for refractory cases of childhood nephrotic syndrome.","volume":"26","author":"Kari","year":"2011","journal-title":"Pediatr Nephrol"},{"key":"B15-20230816","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1681\/ASN.2011080775","article-title":"Rituximab in children with resistant idiopathic nephrotic syndrome.","volume":"23","author":"Magnasco","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B16-20230816","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.2215\/CJN.00570109","article-title":"Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis.","volume":"4","author":"Fernandez-Fresnedo","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"B17-20230816","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nri2729","article-title":"Effector and regulatory B cells: Modulators of CD4+ T cell immunity.","volume":"10","author":"Lund","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B18-20230816","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1111\/ajt.12220","article-title":"A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function.","volume":"13","author":"Kamburova","year":"2013","journal-title":"Am J Transplant"},{"key":"B19-20230816","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1182\/blood-2007-02-068999","article-title":"Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic 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therapeutic approach.","volume":"11","author":"Daoussis","year":"2004","journal-title":"Clin Diagn Lab Immunol"},{"key":"B37-20230816","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/nm1293","article-title":"A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles.","volume":"11","author":"Chattopadhyay","year":"2005","journal-title":"Nat Med"},{"key":"B38-20230816","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/ni833","article-title":"B cells regulate autoimmunity by provision of IL-10.","volume":"3","author":"Fillatreau","year":"2002","journal-title":"Nat Immunol"},{"key":"B39-20230816","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1074-7613(02)00274-1","article-title":"Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d 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