Journal
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
Volume 64, Issue 2, Pages 107-113Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.retram.2016.03.004
Keywords
Autoimmune disease; Hematopoietic stem cell; Autologous transplantation; Immune reconstitution; T-cell receptor diversity; Regulatory T-cells
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Funding
- Sao Paulo State Research Foundation (Fapesp) [13/18678-3, 14/20922-2]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/18678-3] Funding Source: FAPESP
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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. (C) 2016 Elsevier Masson SAS. All rights reserved.
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