AUTHOR=de Azevedo Júlia Teixeira Cottas , Costa Thalita Cristina de Mello , Lima Keli Cristina , Maciel Thiago Trovati , Palma Patrícia Vianna Bonini , Darrigo-Júnior Luiz Guilherme , Setanni Grecco Carlos Eduardo , Stracieri Ana Beatriz P. L. , Elias Juliana Bernardes , Pieroni Fabiano , Guerino-Cunha Renato Luiz , Pinto Ana Cristina Silva , De Santis Gil Cunha , Covas Dimas Tadeu , Hermine Olivier , Simões Belinda Pinto , Oliveira Maria Carolina , Malmegrim Kelen Cristina Ribeiro TITLE=Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.774442 DOI=10.3389/fimmu.2021.774442 ISSN=1664-3224 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.