{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:23:38Z","timestamp":1793291018815,"version":"4.5.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"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>B cell depleting therapies permit immunosuppressive drug withdrawal and maintain remission in patients with frequently relapsing nephrotic syndrome (FRNS) or steroid\u2013dependent nephrotic syndrome (SDNS), but lack of biomarkers for treatment failure. Post-depletion immune cell reconstitution may identify relapsing patients, but previous characterizations suffered from methodological limitations of flow cytometry. Time-of-flight mass cytometry (CyTOF) is a comprehensive analytic modality that simultaneously quantifies over 40 cellular markers. Herein, we report CyTOF-enabled immune cell comparisons over a 12-month period from 30 children with SDNS receiving B cell depleting therapy who either relapsed (n = 17) or remained stable (n = 13). Anti-CD20 treatment depleted all B cells subsets and CD20 depleting agent choice (rituximab<jats:italic>vs<\/jats:italic>ofatumumab) did not affect B cell subset recovery. Despite equal total numbers of B cells, 5 subsets of B cells were significantly higher in relapsing individuals; all identified subsets of B cells were class-switched. T cell subsets (including T follicular helper cells and regulatory T cells) and other major immune compartments were largely unaffected by B cell depletion, and similar between relapsing and stable children. In conclusion, CyTOF analysis of immune cells from anti-CD20 antibody treated patients identifies class-switched B cells as the main subset whose expansion associates with disease relapse. Our findings set the basis for future studies exploring how identified subsets can be used to monitor treatment response and improve our understanding of the pathogenesis of the disease.<\/jats:p>","DOI":"10.3389\/fimmu.2021.726428","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T04:32:49Z","timestamp":1632198769000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["CyTOF-Enabled Analysis Identifies Class-Switched B Cells as the Main Lymphocyte Subset Associated With Disease Relapse in Children With Idiopathic Nephrotic Syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Miguel","family":"Fribourg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Cioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GianMarco","family":"Ghiggeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cantarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"Leventhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Budge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Bin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo V.","family":"Riella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Colucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Vivarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Angeletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Perin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cravedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic Syndrome in Childhood","volume":"362","author":"Eddy","year":"2003","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/01.asn.0000067648.75923.68","article-title":"Podocyte Differentiation and Hereditary Proteinuria\/Nephrotic Syndromes","author":"Gubler","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2310-x","article-title":"Kidney Disease: Improving Global O: Treatment of Steroid-Sensitive Nephrotic Syndrome: New Guidelines From KDIGO","volume":"28","author":"Lombel","year":"2013","journal-title":"Pediatr Nephrol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604043341402","article-title":"Circulating Factor Associated With Increased Glomerular Permeability to Albumin in Recurrent Focal Segmental Glomerulosclerosis","volume":"334","author":"Savin","year":"1996","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(74)91880-7","article-title":"Pathogenesis of Lipoid Nephrosis: A Disorder of T-Cell Function","volume":"2","author":"Shalhoub","year":"1974","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012070646","article-title":"Extending Prednisolone Treatment Does Not Reduce Relapses in Childhood Nephrotic Syndrome","volume":"24","author":"Teeninga","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V85769","article-title":"Prognostic Significance of the Early Course of Minimal Change Nephrotic Syndrome: Report of the International Study of Kidney Disease in Children","volume":"8","author":"Tarshish","year":"1997","journal-title":"J Am Soc Nephrol"},{"key":"B8","article-title":"Nephrotic Syndrome in Children: A Randomized Trial Comparing Two Prednisone Regimens in Steroid-Responsive Patients Who Relapse Early. 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