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.
Highlights
Sickle cell disease (SCD) is one of the most prevalent monogenic disease in the world caused by a one point mutation at position 6 of the b-globin gene, which results in abnormal production of hemoglobin S [1,2,3]
This study included 32 SCD patients who were treated with allogeneic HSCT
When patients were clustered according to engraftment, the graft failure group had lower red blood cell counts, hematocrit, and hemoglobin levels at 6 and 24 months after HSCT and higher reticulocyte counts at 24 and 36 months compared to the engraftment group (Figures 1B, D, F, H)
Summary
Sickle cell disease (SCD) is one of the most prevalent monogenic disease in the world caused by a one point mutation at position 6 of the b-globin gene, which results in abnormal production of hemoglobin S [1,2,3]. In SCD patients, hemoglobin S polymerizes at low oxygen levels, resulting in altered cellular architecture of red blood cells (RBC) and exposure of adhesion molecules on the cell surface, including CD36, CD47, CD49d, and BCAM/Lu [11,12,13,14]. In this work we assessed red blood cell adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allo-HSCT. Aliquots of diluted red blood cells (100mL) were incubated with 5 mL of monoclonal antibodies or control isotypes for 15 minutes in the dark, at room temperature. This model allows multiple longitudinal observations per individual across a baseline period and subsequent time points after transplantation.
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