title: Resetting the immune system with immunoablation and autologous haematopoietic stem cell transplantation in autoimmune diseases.
abstract: Over the past 20 years, immunoablation followed by transplantation of autologous haematopoietic stem cells (ASCT) has emerged as a promising treatment option for patients with severe forms of autoimmune diseases (ADs) that insufficiently respond to standard immunosuppressive or novel biologic treatment. Meanwhile, mechanistic studies have provided the proof-of-concept that the long-term, treatment-free remissions achieved by ASCT are associated with the eradication of the autoreactive immunologic memory and a fundamental reconfiguration of the immune system. The latter comprises regeneration of naive B cells and a stable thymic reactivation with re-emergence of thymic-derived naive T cells, including Foxp3+ regulatory T cells, with new antigen receptors, i.e. immune reset. In this article, we discuss mechanistic studies that investigated how such immune renewal after ASCT may rewire a faulty immune system in ADs into a self-tolerant state, to induce long-term remissions.
authors: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin; and German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Autoimmunology Group, Berlin, Germany. tobias.alexander@charite.de.
authors: Tobias
authors: T
authors: Alexander
authors: Department of Haematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Germany.
authors: Renate
authors: R
authors: Arnold
authors: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin; and German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Autoimmunology Group, Berlin, Germany.
authors: Falk
authors: F
authors: Hiepe
authors: German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Cell Biology Group, Berlin, Germany.
authors: Andreas
authors: A
authors: Radbruch
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000601:surgery*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010641:Phenotype; D012074:Remission Induction; D017634:Self Tolerance; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents