Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases: From Mechanistic Insights to Biomarkers

Author(s)

Ribeiro Malmegrim, Kelen Cristina ^{[1, 2]} ; Lima-Junior, Joao Rodrigues ^{[2, 3]} ; Marliere Arruda, Lucas Coelho ^{[4, 5]} ; Cottas de Azevedo, Julia Teixeira ^{[6, 5]} ; Vilela de Oliveira, Gislane Lelis ^[7] ; Oliveira, Maria Carolina ^{[2, 5]}

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Reg Hemotherapy Ctr, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Biosci Appl Pharm Program, Ribeirao Preto - Brazil

^[4] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm - Sweden

^[5] Univ Sao Paulo, Div Rheumatol Allergy Immunol & Immunotherapy, Dept Internal Med, Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Basic & Appl Immunol Program, Ribeirao Preto - Brazil

^[7] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci IBILCE, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 9, NOV 16 2018.
• Web of Science Citations: 1

Abstract

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 immunemonitoring studies and combined therapeutic interventions to further improve the AHSCT protocols and their therapeutic efficacy. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC