Autologous hematopoietic stem cell transplantation for autoimmune diseases: From mechanistic insights to biomarkers
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2018-11-16
Autores
Malmegrim, Kelen Cristina Ribeiro
Lima-Júnior, João Rodrigues
Arruda, Lucas Coelho Marlière
De Azevedo, Júlia Teixeira Cottas
De Oliveira, Gislane Lelis Vilela [UNESP]
Oliveira, Maria Carolina
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Phase I/II clinical trials of autologous hematopoietic stem cell transplantation (AHSCT) have led to increased safety and efficacy of this therapy for severe and refractory autoimmune diseases (AD). Recent phase III randomized studies have demonstrated that AHSCT induces long-term disease remission in most patients without any further immunosuppression, with superior efficacy when compared to conventional treatments. Immune monitoring studies have revealed the regeneration of a self-tolerant T and B cell repertoire, enhancement of immune regulatory mechanisms, and changes toward an anti-inflammatory milieu in patients that are responsive to AHSCT. However, some patients reactivate the disease after transplantation due to reasons not yet completely understood. This scenario emphasizes that additional specific immunological interventions are still required to improve or sustain therapeutic efficacy of AHSCT in patients with AD. Here, we critically review the current knowledge about the operating immune mechanisms or established mechanistic biomarkers of AHSCT for AD. In addition, we suggest recommendations for future immune monitoring studies and biobanking to allow discovery and development of biomarkers. In our view, AHSCT for AD has entered a new era and researchers of this field should work to identify robust predictive, prognostic, treatment-response biomarkers and to establish new guidelines for immune monitoring studies and combined therapeutic interventions to further improve the AHSCT protocols and their therapeutic efficacy.
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autoimmune diseases, biomarkers, hematopoietic stem cell transplantation, immune reconstitution, immune tolerance, immunoregulation
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Frontiers in Immunology, v. 9, n. NOV, 2018.