Category: Bone marrow or stem cell transplantation
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.
Joao Lima Junior– PhD student, 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
Lucas CM Arruda– PhD, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Maynara S Gonçalves– Master's-degree student, Program of Graduation on Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo
Julia TC de Azevedo– PhD, Ribeirão Preto Medical School, University of São Paulo
Daniela A Moraes– MD PhD, Division of Clinical Immunology Ribeirao Preto Medical School
Dimas T Covas– Prof. Dr., Center for Cell-based Therapy, Regional Blood Center of Ribeirao Preto, Ribeirao Preto Medical School, University of Sao Paulo
Maria C Oliveira– Prof. Dr., Division of Clinical Immunology Ribeirao Preto Medical School
Kelen CR Malmegrim– Prof. Dr., Program of Graduation on Biosciences and Biotechnology, Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto