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

Autor: Luciana Ribeiro Jarduli‐Maciel, Júlia Teixeira Cottas de Azevedo, Emmanuel Clave, Thalita Cristina de Mello Costa, Lucas Coelho Marlière Arruda, Isabelle Fournier, Patrícia Vianna Bonini Palma, Keli Cristina Lima, Juliana Bernardes Elias, Ana Beatriz PL Stracieri, Fabiano Pieroni, Renato Cunha, Luiz Guilherme Darrigo‐Júnior, Carlos Eduardo Settani Grecco, Dimas Tadeu Covas, Ana Cristina Silva‐Pinto, Gil Cunha De Santis, Belinda Pinto Simões, Maria Carolina Oliveira, Antoine Toubert, Kelen Cristina Ribeiro Malmegrim
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Clinical & Translational Immunology, Vol 11, Iss 4, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2050-0068
DOI: 10.1002/cti2.1389
Popis: Abstract 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 β‐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 allo‐HSCT (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 allo‐HSCT. In addition, the increase of IL‐10‐producing B‐regulatory cells may contribute to improve immune regulation and homeostasis after transplantation.
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