{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:25:15Z","timestamp":1788639915979,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which B-cell dysregulation plays a central pathogenic role beyond autoantibody production. Advances in B-cell biology have led to the development of targeted therapies, including inhibition of the B-cell activating factor (BAFF) pathway. Belimumab, a monoclonal antibody that neutralizes soluble BAFF, modulates B-cell survival signals upstream, promoting progressive immunologic remodeling rather than rapid depletion. This review integrates current knowledge on BAFF-dependent B-cell biology with mechanistic, pharmacokinetic, and clinical data to provide a comprehensive framework for understanding belimumab\u2019s effects in SLE and lupus nephritis (LN). Belimumab preferentially reduces transitional and na\u00efve B cells, while memory B cells show a relative transient increase followed by a gradual return to baseline levels, reflecting redistribution rather than expansion, and long-lived plasma cells are largely unaffected. These effects result in progressive remodeling of B-cell compartment dynamics and contribute to broader modulation of adaptive immune amplification pathways. Pharmacokinetic data support a threshold-based model of BAFF neutralization, with exposure influenced by disease-related factors such as proteinuria in LN. Clinical response is primarily determined by baseline disease biology, with greater benefit observed in patients with serologically active disease and less established organ involvement. Across clinical trials and real-world studies, belimumab reduces disease activity and flares, enables glucocorticoid tapering, and slows organ damage accrual. In LN, it improves renal outcomes and reduces the risk of kidney-related events. Collectively, these findings support belimumab as a disease-modifying therapy in SLE. Further research is needed to refine patient selection and optimize treatment sequencing and combination strategies.<\/jats:p>","DOI":"10.3390\/jcm15083173","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"3173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Belimumab in Systemic Lupus Erythematosus: From B-Cell Biology to Disease Modification"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1262-8072","authenticated-orcid":false,"given":"Marc","family":"Xipell","sequence":"first","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Center for Complex Glomerular Diseases, Spanish Health System (CSUR), 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-7362","authenticated-orcid":false,"given":"Mar\u00eda Cecilia","family":"Garbarino","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Autoimmune Diseases, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Centre for Systemic Autoimmune Diseases of the Catalan (XUEC), Spanish Health System (CSUR), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Serrano del Castillo","sequence":"additional","affiliation":[{"name":"Department of Immunology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Morantes","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Center for Complex Glomerular Diseases, Spanish Health System (CSUR), 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-8107","authenticated-orcid":false,"given":"Carla","family":"Bastida","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Department of Pharmacology, Toxicology and Therapeutical Chemistry, School of Pharmacy, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-6396","authenticated-orcid":false,"given":"Ignasi","family":"Rodr\u00edguez-Pint\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Autoimmune Diseases, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Centre for Systemic Autoimmune Diseases of the Catalan (XUEC), Spanish Health System (CSUR), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8177-702X","authenticated-orcid":false,"given":"Jose A.","family":"G\u00f3mez-Puerta","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Rheumatology, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-0163","authenticated-orcid":false,"given":"Gerard","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Autoimmune Diseases, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Centre for Systemic Autoimmune Diseases of the Catalan (XUEC), Spanish Health System (CSUR), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7582-8476","authenticated-orcid":false,"given":"Luis F.","family":"Quintana","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Center for Complex Glomerular Diseases, Spanish Health System (CSUR), 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-492X","authenticated-orcid":false,"given":"Ricard","family":"Cervera","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Autoimmune Diseases, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Reference Centre for Systemic Autoimmune Diseases of the Catalan (XUEC), Spanish Health System (CSUR), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.rdc.2021.04.006","article-title":"B cells in systemic lupus erythematosus: From disease mechanisms to targeted therapies","volume":"47","author":"Canny","year":"2021","journal-title":"Rheum. 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