{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T07:50:12Z","timestamp":1794469812277,"version":"4.9.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"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>Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1368275","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:54:48Z","timestamp":1710737688000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential"],"prefix":"10.3389","volume":"15","author":[{"given":"Haodong","family":"Shang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7196\/SAMJ.2023.v113i3.780","article-title":"Autoimmune encephalitis : Part 1 (Epidemiology, Pathophysiology and Clinical spectrum)","volume":"113","author":"Hiesgen","year":"2023","journal-title":"South Afr Med J = Suid-Afrikaanse tydskrif vir geneeskunde"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25131","article-title":"Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis","volume":"83","author":"Dubey","year":"2018","journal-title":"Ann neurology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"577867","DOI":"10.1016\/j.jneuroim.2022.577867","article-title":"Pathogenic mechanisms in neuronal surface autoantibody-mediated encephalitis","volume":"368","author":"Gill","year":"2022","journal-title":"J neuroimmunology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181cb0968","article-title":"Anti-N-methyl-D-aspartate receptor antibodies: a potentially treatable cause of encephalitis in the intensive care unit","volume":"38","author":"Davies","year":"2010","journal-title":"Crit Care Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00603","article-title":"Mechanisms of autoantibody-induced pathology","volume":"8","author":"Ludwig","year":"2017","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0672-1","article-title":"Multiple inducers and novel roles of autoantibodies against the obligatory NMDAR subunit NR1: a translational study from chronic life stress to brain injury","volume":"26","author":"Pan","year":"2021","journal-title":"Mol Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"102876","DOI":"10.1016\/j.msard.2021.102876","article-title":"Psychosocial stress, blood brain barrier and the development of anti N-methyl-D-aspartate receptor (NMDAR) encephalitis","volume":"50","author":"Vahabi","year":"2021","journal-title":"Multiple sclerosis related Disord"},{"key":"B9","doi-asserted-by":"publisher","first-page":"26331055221114817","DOI":"10.1177\/26331055221114817","article-title":"At the root of 3 \"Long\" Diseases: persistent antigens inflicting chronic damage on the brain and other organs in gulf war illness, long-COVID-19, and chronic fatigue syndrome","volume":"17","author":"James","year":"2022","journal-title":"Neurosci Insights"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00430","article-title":"Ectopic lymphoid structures: powerhouse of autoimmunity","volume":"7","author":"Corsiero","year":"2016","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000034237","article-title":"Abundant infiltration of B cells and plasma cells in brain biopsy of a male patient with severe anti-NMDA receptor encephalitis: A case report","volume":"102","author":"Wei","year":"2023","journal-title":"Medicine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26223","article-title":"Neuropathological variability within a spectrum of NMDAR-encephalitis","volume":"90","author":"Zrzavy","year":"2021","journal-title":"Ann neurology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325300","article-title":"Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management","volume":"92","author":"Abboud","year":"2021","journal-title":"J neurology neurosurgery Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3188","article-title":"Use and safety of immunotherapeutic management of N-methyl-d-aspartate receptor antibody encephalitis: A meta-analysis","volume":"78","author":"Nosadini","year":"2021","journal-title":"JAMA neurology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00943-z","article-title":"Treatment options in refractory autoimmune encephalitis","volume":"36","author":"Dinoto","year":"2022","journal-title":"CNS Drugs"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1126421","article-title":"B cell depletion therapies in autoimmune diseases: Monoclonal antibodies or chimeric antigen receptor-based therapy","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/ane.13291","article-title":"Efficacy and safety of rituximab in autoimmune encephalitis: A meta-analysis","volume":"142","author":"Nepal","year":"2020","journal-title":"Acta neurologica Scandinavica"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001088","article-title":"Rituximab treatment and long-term outcome of patients with autoimmune encephalitis: real-world evidence from the GENERATE registry","volume":"8","author":"Thaler","year":"2021","journal-title":"Neurology(R) neuroimmunology Neuroinflamm"},{"key":"B19","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s40120-022-00327-x","article-title":"Low recruitment in a double-blind, placebo-controlled trial of ocrelizumab for autoimmune encephalitis: A case series and review of lessons learned","volume":"11","author":"Blackburn","year":"2022","journal-title":"Neurol Ther"},{"key":"B20","doi-asserted-by":"publisher","first-page":"578062","DOI":"10.1016\/j.jneuroim.2023.578062","article-title":"The therapeutic effect of ofatumumab in autoimmune encephalitis: A case series","volume":"377","author":"Zhou","year":"2023","journal-title":"J neuroimmunology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.602102","article-title":"Case report: daratumumab in a patient with severe refractory anti-NMDA receptor encephalitis","volume":"11","author":"Ratuszny","year":"2020","journal-title":"Front neurology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09585-6","article-title":"Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis","volume":"267","author":"Scheibe","year":"2020","journal-title":"J neurology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15266","article-title":"Daratumumab for treatment-refractory antibody-mediated diseases in neurology","volume":"29","author":"Scheibe","year":"2022","journal-title":"Eur J neurology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"577586","DOI":"10.1016\/j.jneuroim.2021.577586","article-title":"Bortezomib in anti-N-Methyl-d-Aspartate-Receptor (NMDA-R) encephalitis: A systematic review","volume":"356","author":"Dinoto","year":"2021","journal-title":"J neuroimmunology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.143","article-title":"Successful treatment of anti-Caspr2 syndrome by interleukin 6 receptor blockade through tocilizumab","volume":"70","author":"Krogias","year":"2013","journal-title":"JAMA neurology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0442-6","article-title":"Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study","volume":"13","author":"Lee","year":"2016","journal-title":"Neurotherapeutics"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00921-7","article-title":"Teratoma removal, steroid, IVIG, rituximab and tocilizumab (T-SIRT) in anti-NMDAR encephalitis","volume":"18","author":"Lee","year":"2021","journal-title":"Neurotherapeutics"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1004795","article-title":"Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic","volume":"14","author":"de S\u00e8ze","year":"2023","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4161\/mabs.22771","article-title":"Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties","volume":"5","author":"Klein","year":"2013","journal-title":"mAbs"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3100","article-title":"Ofatumumab","volume":"9","author":"Keating","year":"2010","journal-title":"Nat Rev Drug discovery"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.1.10789","article-title":"Evolution of anti-CD20 monoclonal antibody therapeutics in oncology","volume":"2","author":"Oflazoglu","year":"2010","journal-title":"mAbs"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-694356","article-title":"Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy","volume":"128","author":"Bhoj","year":"2016","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1756286418761697","DOI":"10.1177\/1756286418761697","article-title":"B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets","volume":"11","author":"Forsthuber","year":"2018","journal-title":"Ther Adv neurological Disord"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/jcm5120107","article-title":"Inebilizumab, a B cell-depleting anti-CD19 antibody for the treatment of autoimmune neurological diseases: insights from preclinical studies","volume":"5","author":"Chen","year":"2016","journal-title":"J Clin Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30760","article-title":"Effect of CD38 on B-cell function and its role in the diagnosis and treatment of B-cell-related diseases","volume":"237","author":"Zeng","year":"2022","journal-title":"J Cell Physiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0679-9","article-title":"Clinical pharmacokinetics and pharmacodynamics of bortezomib","volume":"58","author":"Tan","year":"2019","journal-title":"Clin pharmacokinetics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13078","article-title":"The short-term efficacy of combined treatments targeting B cell and plasma cell in severe and refractory Anti-N-methyl-D-aspartate receptor encephalitis: Two case reports","volume":"25","author":"Zhang","year":"2019","journal-title":"CNS Neurosci Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.03.023","article-title":"Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases","volume":"585","author":"Tanaka","year":"2011","journal-title":"FEBS letters"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.09.004","article-title":"Targeting interleukin-6 in inflammatory autoimmune diseases and cancers","volume":"141","author":"Yao","year":"2014","journal-title":"Pharmacol Ther"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01380-2","article-title":"Satralizumab: first approval","volume":"80","author":"Heo","year":"2020","journal-title":"Drugs"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5084","DOI":"10.1016\/j.cell.2023.10.001","article-title":"Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells","volume":"186","author":"Reincke","year":"2023","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014738","article-title":"Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1\/2 clinical trial","volume":"139","author":"Frigault","year":"2022","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3003","article-title":"The safety and side effects of monoclonal antibodies","volume":"9","author":"Hansel","year":"2010","journal-title":"Nat Rev Drug discovery"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06704-2","article-title":"Latent human herpesvirus 6 is reactivated in CAR T cells","volume":"623","author":"Lareau","year":"2023","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"R204","DOI":"10.1186\/ar3179","article-title":"Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus","volume":"12","author":"Daridon","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"B47","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/nrrheum.2016.165","article-title":"Systemic lupus erythematosus: Epratuzumab not effective in phase III trials","volume":"12","author":"Onuora","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/art.39856","article-title":"Efficacy and safety of epratuzumab in moderately to severely active systemic lupus erythematosus: results from two phase III randomized, double-blind, placebo-controlled trials","volume":"69","author":"Clowse","year":"2017","journal-title":"Arthritis Rheumatol (Hoboken NJ)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1002\/art.21526","article-title":"Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes","volume":"54","author":"Matsushita","year":"2006","journal-title":"Arthritis rheumatism"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.12.035","article-title":"B cell alterations during BAFF inhibition with belimumab in SLE","volume":"40","author":"Ramsk\u00f6ld","year":"2019","journal-title":"EBioMedicine"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-023-06624-z","article-title":"The imbalance between Bregs, Tfh, and Tregs in patients with anti-N-methyl-D-aspartate receptor encephalitis","volume":"44","author":"Li","year":"2023","journal-title":"Neurological Sci"},{"key":"B52","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.imlet.2013.07.005","article-title":"The CD40\/CD40L system: a new therapeutic target for disease","volume":"153","author":"Zhang","year":"2013","journal-title":"Immunol Lett"},{"key":"B53","doi-asserted-by":"publisher","first-page":"577762","DOI":"10.1016\/j.jneuroim.2021.577762","article-title":"Dysregulated CD40 and CD40 ligand expression in anti-N-methyl-d-aspartate receptor encephalitis","volume":"362","author":"Ma","year":"2022","journal-title":"J neuroimmunology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1368275\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:54:51Z","timestamp":1710737691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1368275\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2024.1368275"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1368275","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]},"article-number":"1368275"}}