Resetting the immune response after autologous hematopoietic stem cell transplantation for autoimmune diseases.
Autologous hematopoietic stem cell transplantation (AHSCT) is currently investigated as treatment for severe and refractory autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), Crohn's disease (CD) and systemic lupus erythematosus. Randomized clinical trials in MS, SSc and CD have shown the efficacy of AHSCT to promote control of disease activity and progression, when compared to conventional treatment. The use of high dose immunosuppressive conditioning is essential to eliminate the autoimmune repertoire, and the re-infusion of autologous hematopoietic stem cells avoids long-term leucopenia by reconstitution of both immune and hematological systems. Recent studies showed that AHSCT is able to deplete the autoimmune compartment and further promote the formation of a new auto-tolerant immune repertoire, reducing the inflammatory milieu and leading to long-term clinical remission without any complementary post-graft treatment. Deep knowledge about the mechanisms of action related to AHSCT-induced remission is required for the management of possible post-AHSCT relapse and improvement of clinical protocols. This paper will review the mechanisms enrolled in the immune response resetting promoted by AHSCT in patients with autoimmune diseases.
Center for Cell-based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: lucascma@usp.br.
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Arruda
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
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Clave
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
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Moins-Teisserenc
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
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Douay
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Unité Clinique de Médecine Interne, Maladies Autoimmunes et Pathologie Vasculaire, UF 04, Hôpital Saint-Louis, AP-HP, Assistance Publique des Hôpitaux de Paris, 75010 Paris, France.
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Farge
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
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Toubert
D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D060966:Clonal Selection, Antigen-Mediated; D005544:Forecasting; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014182:Transplantation, Autologous
D011948:Receptors, Antigen, T-Cell
Autoimmune disease; Autologous transplantation; Hematopoietic stem cell; Immune reconstitution; Regulatory T-cells; T-cell receptor diversity