Arbuckle, M. R. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533 (2003).
Schett, G., Nagy, G., Krönke, G. & Mielenz, D. B-cell depletion in autoimmune diseases. Ann. Rheum. Dis. 83, 1409–1420 (2024).
Barnett, L. G. et al. B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation. J. Immunol. 192, 3607–3617 (2014).
Uzzan, M. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Nat. Med. 28, 766–779 (2022).
Livanos, A. E. et al. Anti-Integrin αvβ6 Autoantibodies are a novel biomarker that antedate ulcerative colitis. Gastroenterology 164, 619–629 (2023).
Duddy, M. et al. Distinct effector cytokine profiles of memory and naive human B-cell subsets and implication in multiple sclerosis. J. Immunol. 178, 6092–6099 (2007).
Rosser, E. C. & Mauri, C. Regulatory B-cells: origin, phenotype, and function. Immunity 42, 607–612 (2015).
Schett, G., McInnes, I. B. & Neurath, M. F. Reframing immune-mediated inflammatory diseases through signature cytokine hubs. N. Engl. J. Med. 385, 628–639 (2021).
Furie, R. A. et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N. Engl. J. Med. 392, 1471–1483 (2025).
Sullivan, K. M. et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N. Engl. J. Med. 378, 35–47 (2018).
Kochenderfer, J. N. et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 116, 4099–4102 (2010).
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A. & June, C. H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365, 725–733 (2011).
Davenport, A. J. et al. CAR-T-cells inflict sequential killing of multiple tumor target cells. Cancer Immunol. Res. 3, 483–494 (2015).
Mujtahedi, S. S. et al. Bone marrow derived long-lived plasma cell phenotypes are heterogeneous and can change in culture. Transpl. Immunol. 75, 101726 (2022).
Flores-Montero, J. et al. Immunophenotype of normal vs. myeloma plasma cells: toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin. Cytom. 90, 61–72 (2016).
Mackensen, A. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat. Med. 28, 2124–2132 (2022).
Muller, F. et al. CD19 CAR T-Cell therapy in autoimmune disease – a case series with follow-up. N. Engl. J. Med. 390, 687–700 (2024).
Kansal, R. et al. Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Sci. Transl. Med. 11, eaav1648 (2019).
Mougiakakos, D. et al. T cells in refractory systemic lupus erythematosus. N. Engl. J. Med. 385, 567–569 (2021).
Nicholson, I. C. et al. Construction and characterisation of a functional CD19 specific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma. Mol. Immunol. 34, 1157–1165 (1997).
Wang, W. et al. BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial. Ann. Rheum. Dis. 83, 1304–1314 (2024).
Wang, Y. et al. Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) in adults with moderately to severely active systemic lupus erythematosus: a phase I dose-escalation study. J. Autoimmun. 157, 103489 (2025).
Feng, J. et al. Co-infusion of CD19-targeting and BCMA-targeting CAR-T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial. Nat. Med. 31, 3725–3736 (2025).
Gerber, J. M. et al. Successful autologous CD19 CAR T cell therapy following severe lupus flare during immunosuppressive washout in refractory lupus nephritis. Lupus Sci. Med. 12, e001742 (2025).
Shu, J. et al. Safety and clinical efficacy of Relmacabtagene autoleucel (relma-cel) for systemic lupus erythematosus: a phase 1 open-label clinical trial. EClinicalMedicine 83, 103229 (2025).
Bergmann, C. et al. Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann. Rheum. Dis. 82, 1117–1120 (2023).
Auth, J. et al. CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series. Lancet Rheumatol. 7, 83–93 (2025).
Merkt, W. et al. Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis. Ann. Rheum. Dis. 83, 543–546 (2024).
Müller, F. et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. Lancet 401, 815–818 (2023).
Lidar, M. et al. CD-19 CAR-T cells for polyrefractory rheumatoid arthritis. Ann. Rheum. Dis. 84, 370–372 (2025).
Haghikia, A. et al. Clinical efficacy and autoantibody seroconversion with CD19-CAR T cell therapy in a patient with rheumatoid arthritis and coexisting myasthenia gravis. Ann. Rheum. Dis. 83, 1597–1598 (2024).
Minopoulou, I. et al. Anti-CD19 CAR T cell therapy induces antibody seroconversion and complete B cell depletion in the bone marrow of a therapy-refractory patient with ANCA-associated vasculitis. Ann. Rheum. Dis. 84, e4–e7 (2025).
Qin, C. et al. Anti-BCMA CAR-T therapy in patients with progressive multiple sclerosis. Cell 188, 6414–6423 (2025).
Fischbach, F. et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med 5, 550–558 (2024).
Haghikia, A., Hegelmaier, T. & Wolleschak, D. Anti-CD19 CAR T cells for refractory myasthenia gravis. Lancet Neurol. 22, 1104–1105 (2023).
Zhang, Y. et al. Bispecific BCMA/CD19 targeted CAR-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: a case report. J. Neurol. 271, 4655–4659 (2024).
Zhang, Y. et al. Anti-BCMA/CD19 CAR T cell therapy in patients with refractory generalized myasthenia gravis: a single-arm, phase 1 trial. EClinicalMedicine 90, 103621 (2025).
Chahin, N. et al. Durability of response to B-cell maturation antigen-directed mRNA cell therapy in myasthenia gravis. Ann. Clin. Transl. Neurol. 12, 2358–2366 (2025).
Motte, J. et al. Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells. Neuron 112, 1757–1763 (2024).
Qin, C. et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduct. Target. Ther. 8, 5 (2023).
Faissner, S. et al. Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome. Proc. Natl Acad. Sci. USA 121, e2403227121 (2024).
Hegelmaier, T. et al. Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis. Med 6, 100776 (2025).
Müller, F. et al. CD19 CAR T-cell therapy in multidrug-resistant ulcerative colitis. N. Engl. J. Med. 393, 1239–1241 (2025).
Trautmann-Grill, K. et al. Salvage treatment of multi-refractory primary immune thrombocytopenia with CD19 CAR T cells. Lancet 405, 25–28 (2025).
Li, M. et al. Anti-CD19 CAR T Cells in refractory immune thrombocytopenia of SLE. N. Engl. J. Med. 391, 376–378 (2024).
Krickau, T. et al. CAR T-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis. Lancet 403, 1627–1630 (2024).
De Benedetti, F., Diomedi Camassei, F. & Locatelli, F. CAR T-cell therapy in autoimmune disease. N. Engl. J. Med. 390, 1629 (2024).
Nicolai, R. et al. Autologous CD19-targeting CAR T cells in a patient with refractory juvenile dermatomyositis. Arthritis Rheumatol. 76, 1560–1565 (2024).
He, X. et al. Treatment of two pediatric patients with refractory systemic lupus erythematosus using CD19-targeted CAR T-cells. Autoimmun. Rev. 24, 103692 (2025).
Becilli, M. et al. Anti-CD19 CAR T cells for pediatric patients with treatment-refractory autoimmune diseases. Nat. Med. 32, 1105–1117 (2026).
Muller, F. et al. Safety and preliminary efficacy of zorpocabtagene-autoleucel in systemic autoimmune diseases. Nat. Med. (2026, in press).
Mao, Y. et al. Bicistronic-CD19/22 chimeric antigen receptor T-cell therapy for childhood refractory lupus nephritis. Kid. Int. Rep. 13, 53–61 (2025).
Greco, R. et al. Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee. EClinicalMedicine 69, 102476 (2024).
Hsieh, E. W. Y. et al. Key considerations for advancing chimeric antigen receptor (CAR) T-cell therapy for systemic lupus erythematosus (SLE): a multi-partner/disciplinary working group perspective. RMD Open 11, e005866 (2025).
Müller, F. et al. BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells. Nat. Med. 31, 1793–1797 (2025).
Wang, X. et al. Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell 187, 4890–4904 (2024).
Wang, X. et al. An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis. Cell 188, 4225–4238 (2025).
Wang, X. et al. Allogeneic CD19-targeting T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial. Nat. Med. 31, 3713–3724 (2025).
Wang, D. et al. Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission. Med 6, 100749 (2025).
Gao, J. et al. Efficacy and safety of allogeneic CD19 CAR NK-cell therapy in systemic lupus erythematosus: a case series in China. Lancet 406, 2968–2979 (2026).
Lee, D. W. et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol. Blood Marrow Transplant. 25, 625–638 (2019).
Rejeski, K. et al. Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood 142, 865–877 (2023).
Fried, S. et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 54, 1643–1650 (2019).
Müller, F. et al. Comparison of the safety profiles of CD19-targeting CAR T-cell therapy in patients with SLE and B-cell lymphoma. Blood 146, 1088–1095 (2025).
Hagen, M. et al. Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease: an observational study. Lancet Rheumatol. 7, 424–433 (2025).
Yafasova, A. et al. Long-term cardiovascular outcomes in systemic lupus erythematosus. J. Am. Coll. Cardiol. 77, 1717–1727 (2021).
Tamirou, F. et al. Brief Report: The Euro-lupus low-dose intravenous cyclophosphamide regimen does not impact the ovarian reserve, as measured by serum levels of anti-Müllerian hormone. Arthritis Rheumatol. 69, 1267–1271 (2017).
Ghilardi, G. et al. T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nat. Med. 30, 984–989 (2024).
Hamilton, M. P. et al. Risk of second tumors and T-cell lymphoma after CAR T-cell therapy. N. Engl. J. Med. 390, 2047–2060 (2024).
Chihara, D., Dores, G. M., Flowers, C. R. & Morton, L. M. The bidirectional increased risk of B-cell lymphoma and T-cell lymphoma. Blood 138, 785–789 (2021).
Tur, C. et al. CD19-CAR T-cell therapy induces deep tissue depletion of B cells. Ann. Rheum. Dis. 84, 106–114 (2025).
Tur, C. et al. Effects of different B-cell-depleting strategies on the lymphatic tissue. Ann. Rheum. Dis. 84, 2065–2074 (2025).
Wilhelm, A. et al. Selective CAR T cell-mediated B cell depletion suppresses IFN signature in SLE. JCI Insight 9, e179433 (2024).
Garantziotis, P. et al. Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus. Ann. Rheum. Dis. 85, 153–163 (2025).
Taubmann, J. et al. Effects of CD19 CAR T cell therapy on quality of life and direct healthcare costs in systemic lupus erythematosus: a preliminary analysis. J. Rheumatol. 53, 33–37 (2025).
Hunter, T. L. et al. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science 388, 1311–1317 (2025).
Wang, Q. et al. In vivo CD19 CAR T-cell therapy for refractory systemic lupus erythematosus. N. Engl. J. Med. 393, 1542–1544 (2025).
Xu, J. et al. In-vivo B cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma. Lancet 406, 228–231 (2025).
Fu, Y. et al. Genetically modified CD19-targeting IL-15 secreting NK cells for the treatment of systemic lupus erythematosus. Ann. Rheum. Dis. 84, 1811–1821 (2025).
Li, Y. et al. Fourth-generation chimeric antigen receptor T-cell therapy is tolerable and efficacious in treatment-resistant rheumatoid arthritis. Cell Res. 35, 220–223 (2025).
Cappione, A. J., Pugh-Bernard, A. E., Anolik, J. H. & Sanz, I. Lupus IgG VH4.34 antibodies bind to a 220 kDa glycoform of CD45/B220 on the surface of human B lymphocytes. J. Immunol. 172, 4298–4307 (2004).
Ellebrecht, C. T. et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 353, 179–184 (2016).
Cohen, I. J. et al. Chimeric antigen receptor T cells against IGHV4-34 B cell receptor specifically eliminate neoplastc and autoimmune B cells. Sci. Transl. Med. 18, eadr9382 (2026).
Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022).
Britanova, O. V. et al. Targeted depletion of TRBV9+ T cells as immunotherapy in a patient with ankylosing spondylitis. Nat. Med. 29, 2731–2736 (2023).
Rosado-Sánchez, I. et al. Tregs integrate native and CAR-mediated costimulatory signals for control of allograft rejection. JCI Insight 8, e167215 (2023).
Doglio, M. et al. Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in systemic lupus erythematosus. Nat. Commun. 15, 2542 (2024).
Kohler M., et al. A phase 1 study of autologous CAR-Treg cells in refractory rheumatoid arthritis: interim report of safety and efficacy. In ACR Convergence 2025 Abstract LB23 (ACR, 2025).
