Frontiers in Immunology (Dec 2021)
Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients
- Júlia Teixeira Cottas de Azevedo,
- Júlia Teixeira Cottas de Azevedo,
- Thalita Cristina de Mello Costa,
- Keli Cristina Lima,
- Keli Cristina Lima,
- Thiago Trovati Maciel,
- Thiago Trovati Maciel,
- Patrícia Vianna Bonini Palma,
- Luiz Guilherme Darrigo-Júnior,
- Luiz Guilherme Darrigo-Júnior,
- Carlos Eduardo Setanni Grecco,
- Ana Beatriz P. L. Stracieri,
- Juliana Bernardes Elias,
- Fabiano Pieroni,
- Renato Luiz Guerino-Cunha,
- Renato Luiz Guerino-Cunha,
- Ana Cristina Silva Pinto,
- Gil Cunha De Santis,
- Dimas Tadeu Covas,
- Dimas Tadeu Covas,
- Olivier Hermine,
- Olivier Hermine,
- Belinda Pinto Simões,
- Maria Carolina Oliveira,
- Maria Carolina Oliveira,
- Kelen Cristina Ribeiro Malmegrim,
- Kelen Cristina Ribeiro Malmegrim
Affiliations
- Júlia Teixeira Cottas de Azevedo
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Júlia Teixeira Cottas de Azevedo
- Graduate Program in Basic and Applied Immunology of the Ribeirão Preto Medicinal School, University of São Paulo, Ribeirão Preto, Brazil
- Thalita Cristina de Mello Costa
- Bone Marrow Transplantation and Cellular Therapy Unit, University Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Keli Cristina Lima
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Keli Cristina Lima
- Graduate Program in Bioscience and Biotechnology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
- Thiago Trovati Maciel
- Institut national de la santé et de la recherche médicale (INSERM) Unité mixte de recherche (UMR) 1163, Centre national de la recherche scientifique (CNRS) Equipe de Recherche Labellisée (ERL) 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France
- Thiago Trovati Maciel
- Imagine Institute, Université Paris Descartes, Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France
- Patrícia Vianna Bonini Palma
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Luiz Guilherme Darrigo-Júnior
- Bone Marrow Transplantation and Cellular Therapy Unit, University Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Luiz Guilherme Darrigo-Júnior
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Carlos Eduardo Setanni Grecco
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Ana Beatriz P. L. Stracieri
- Bone Marrow Transplantation and Cellular Therapy Unit, University Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Juliana Bernardes Elias
- Bone Marrow Transplantation and Cellular Therapy Unit, University Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Fabiano Pieroni
- Bone Marrow Transplantation and Cellular Therapy Unit, University Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Renato Luiz Guerino-Cunha
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Renato Luiz Guerino-Cunha
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Ana Cristina Silva Pinto
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Gil Cunha De Santis
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Dimas Tadeu Covas
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Dimas Tadeu Covas
- Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Olivier Hermine
- Institut national de la santé et de la recherche médicale (INSERM) Unité mixte de recherche (UMR) 1163, Centre national de la recherche scientifique (CNRS) Equipe de Recherche Labellisée (ERL) 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Paris, France
- Olivier Hermine
- Imagine Institute, Université Paris Descartes, Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France
- Belinda Pinto Simões
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Maria Carolina Oliveira
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Maria Carolina Oliveira
- Department of Internal Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Kelen Cristina Ribeiro Malmegrim
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Kelen Cristina Ribeiro Malmegrim
- 0Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
- DOI
- https://doi.org/10.3389/fimmu.2021.774442
- Journal volume & issue
-
Vol. 12
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.
Keywords
- sickle cell disease
- chronic inflammation
- allogeneic hematopoietic stem cell transplantation
- hematological reconstitution
- adhesion molecules
