Bone marrow or stem cell transplantation
Joao Lima Junior
Program of Graduation on Biosciences and Biotechnology, School of Pharmaceutical Sciences/Center for Cell-based Therapy, Regional Blood Center of Ribeirão Preto/University of Sao Paulo
Kelen CR Malmegrim
Program of Graduation on Biosciences and Biotechnology, Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto
Introduction: Autologous hematopoietic stem cell transplantation (AHSCT) is an effective and safe approach to treat systemic sclerosis (SSc) patients refractory to conventional therapy. Aim: To evaluate the reconstitution of B-cell subsets in SSc patients following AHSCT. Methods: Peripheral blood samples were harvested from 24 SSc patients before transplantation and at 30, 60, 120, 180, 360 days post-AHSCT. The immunophenotyping, regulatory B-cell (Breg) IL-10 production and suppressive assays were assessed by flow cytometry. Results: Compared to baseline, naïve B-cells (CD19+CD27-IgD-) significantly decreased counts at 30 days post-AHSCT, followed by an increase at 360 days. There was a transient decrease of non-class-switched memory B-cell (CD19+CD27+IgD+) frequency at 30 days, followed by an increase at 360 days. Mature class-switched memory-B-cells (CD19+CD27+IgD-) and plasma cell (CD19+CD27highIgD-) decreased respectively at 60 and 360 days post-AHSCT, while the frequency of double-negative B-cell (CD19+CD27-IgD-) increased at 30 days post-AHSCT. The subset CD20+CD43+CD27+CD69- showed higher percentage at 30 days, followed by a decrease at 360 days. The Breg CD19+CD24hiCD38hi significantly increased at 360 days, while CD19+CD24hiCD27+ Breg transiently decreased from 30 to 180 days post-AHSCT. The frequency of IL-10-producing Breg increased post-transplantation. After AHSCT the Breg CD19+CD24hiCD38hi recover their ability to suppress cytokine production by Th1 CD4+ T-cell in vitro. Conclusion: Following transplantation, SSc patients displayed increased naive-B-cell and decreased memory B-cells, which might contribute to self-tolerance reestablishment, disease remission and clinical improvement on these patients. SSc patients showed increases of Breg numbers after AHSCT as well as an increase of IL-10 production, suggesting improvements in immunoregulatory mechanisms.