Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients

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Jarduli-Maciel, Luciana Ribeiro ; Cottas de Azevedo, Julia Teixeira ; Clave, Emmanuel ; de Mello Costa, Thalita Cristina ; Marliere Arruda, Lucas Coelho ; Fournier, Isabelle ; Bonini Palma, Patricia Vianna ; Lima, Keli Cristina ; Elias, Juliana Bernardes ; Stracieri, Ana Beatriz P. L. ; Pieroni, Fabiano ; Cunha, Renato ; Darrigo-Junior, Luiz Guilherme ; Settani Grecco, Carlos Eduardo ; Covas, Dimas Tadeu ; Silva-Pinto, Ana Cristina ; De Santis, Gil Cunha ; Simoes, Belinda Pinto ; Oliveira, Maria Carolina ; Toubert, Antoine ; Ribeiro Malmegrim, Kelen Cristina

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL & TRANSLATIONAL IMMUNOLOGY; v. 11, n. 4, p. 16-pg., 2022-01-01.

Resumo

Objectives. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). Here, we comprehensively evaluated the reconstitution of T- and B-cell compartments in 29 SCD patients treated with allo-HSCT and how it correlated with the development of acute graft-versus-host disease (aGvHD). Methods. T-cell neogenesis was assessed by quantification of signal-joint and beta-chain TCR excision circles. B-cell neogenesis was evaluated by quantification of signal-joint and coding-joint K-chain recombination excision circles. T- and B-cell peripheral subset numbers were assessed by flow cytometry. Results. Before alloHSCT (baseline), T-cell neogenesis was normal in SCD patients compared with age-, gender- and ethnicity-matched healthy controls. Following allo-HSCT, T-cell neogenesis declined but was fully restored to healthy control levels at one year post-transplantation. Peripheral T-cell subset counts were fully restored only at 24 months post-transplantation. Occurrence of acute graft-versus-host disease (aGvHD) transiently affected T- and B-cell neogenesis and overall reconstitution of T- and B-cell peripheral subsets. B-cell neogenesis was significantly higher in SCD patients at baseline than in healthy controls, remaining high throughout the follow-up after allo-HSCT. Notably, after transplantation SCD patients showed increased frequencies of IL-10-producing B-regulatory cells and IgM(+) memory B-cell subsets compared with baseline levels and with healthy controls. Conclusion. Our findings revealed that the T- and B-cell compartments were normally reconstituted in SCD patients after alto-HSCT. In addition, the increase of IL-10-producing B-regulatory cells may contribute to improve immune regulation and homeostasis after transplantation. (AU)

• 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: 16/11544-0 - Avaliação da função tímica em pacientes com anemia falciforme após o transplante de células-tronco hematopoiéticas e convencionalmente tratados
• Beneficiário: Luciana Ribeiro Jarduli
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado