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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: RHEUMATOLOGY; v. 60, n. 12, p. 5538-5548, DEC 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 16/24443-7 - Avaliação imunofenotípica, funcional e gênica de subpopulações de células B em pacientes com esclerose sistêmica submetidos ao transplante autólogo de células-tronco hematopoiéticas
• Beneficiário: João Rodrigues Lima Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/20343-3 - Avaliação do repertório de receptores de células B em pacientes com esclerose sistêmica tratados com transplante autólogo de células-tronco hematopoiéticas
• Beneficiário: João Rodrigues Lima Júnior
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado