utologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patient

Author(s)

Lima-Junior, Joao R. ^{[1, 2]} ; Arruda, Lucas C. M. ^[3] ; Goncalves, Maynara S. ^{[1, 4]} ; Dias, Juliana B. E. ^[5] ; Moraes, Daniela A. ^[5] ; Covas, Dimas T. ^[4] ; Simoes, Belinda P. ^[4] ; Oliveira, Maria Carolina ^{[4, 5]} ; Malmegrim, Kelen C. R. ^{[6, 4]}

Affiliation

^[1] Univ Sao Paulo, Ctr Cell Based Therapy, Reg Hemotherapy Ctr, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[2] Sch Pharmaceut Sci Ribeirao Preto, Grad Program Biosci & Biotechnol, Ribeirao Preto - Brazil

^[3] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm - Sweden

^[4] Basic & Appl Immunol Program, Ribeirao Preto - Brazil

^[5] Ribeirao Preto Med Sch, Dept Internal Med, Div Clin Immunol, Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: RHEUMATOLOGY; v. 60, n. 12, p. 5538-5548, DEC 2021.
• Web of Science Citations: 1

Abstract

Objectives. The rationale of autologous haematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells and the infused autologous haematopoietic stem cells promote reconstitution of a naive and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in SSc patients treated with AHSCT. Methods. Peripheral blood was harvested from 22 SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signalling pathways and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry. Results. Naive B cell frequencies increased from 60 to 360 days post-AHSCT compared with pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19(+)CD24(hi)CD38(hi) and CD19(+)CD24(hi)CD27(+) frequencies increased at 180 days. Moreover, the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase increased in B cells reconstituted post-AHSCT. Notably, CD19(+)CD24(hi)CD38(hi) Bregs recovered their ability to suppress production of Th1 cytokines by CD4(+) T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-beta 1-producing B cells decreased following AHSCT. Conclusion. Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to re-establishment of self-tolerance and clinical remission. (AU)

• FAPESP's process: 16/24443-7 - Immunophenotypic, functional and gene evaluation of B cell subsets in patients with systemic sclerosis undergoing autologous hematopoietic stem cell transplantation
• Grantee: João Rodrigues Lima Júnior
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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
• FAPESP's process: 18/20343-3 - Evaluation of B-cell receptor repertoire in systemic sclerosis patients treated with autologous hematopoietic stem cell transplantation
• Grantee: João Rodrigues Lima Júnior
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate