Endothelial injury, F-actin and vitamin-D binding protein after hematopoietic stem cell transplant and association with clinical outcomes
| Autor: | Nicholas J. Gloude, Dana T. Lounder, Stella M. Davies, Adam Lane, Sonata Jodele, Kelly E. Lake, Nathan Luebbering, Kitty M R Perentesis, Sheyar Abdullah, Jeremy D. Rubinstein, Alexandra Duell, Bridget Litts, Nikhil Dole, Christopher E. Dandoy, Martin Hewison |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Thrombotic microangiopathy business.industry Vitamin D-binding protein Binding protein Hematopoietic stem cell macromolecular substances Hematology medicine.disease Filamentous actin 03 medical and health sciences 0302 clinical medicine Endocrinology Graft-versus-host disease medicine.anatomical_structure 030220 oncology & carcinogenesis Internal medicine Medicine Cytokine secretion Stem cell business 030215 immunology |
| Zdroj: | Haematologica. 106:1321-1329 |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Endothelial injury after hematopoietic stem cell transplant is an important initiating factor for early transplant toxicities of thrombotic microangiopathy and acute graft versus host disease. We hypothesized that release of the angiopathic molecule filamentous actin from hematopoietic cells lysed during conditioning prior to stem cell transplant would be associated with clinical outcomes. We detected filamentous actin in the blood of 52% of stem cell transplant recipients in the first 14 days after transplant, and children with detectable filamentous actin had significantly elevated risk of thrombotic microangiopathy (p= 0.03) and non-relapse mortality (p= 0.04). Filamentous actin is cleared from the circulation by vitamin D binding protein so we expected that higher levels of vitamin D binding protein would improve outcomes. In a cohort of 190 children receiving allogeneic transplant, risk of thrombotic microangiopathy was reduced in those with serum concentrations of vitamin D binding protein above the median at day 30 (10% vs 31%, p=0.01), and graft versus host disease and non-relapse mortality were reduced in those with levels above the median at day 100 (3% vs 18%, p=0.04 and 0% vs 15%, p=0.002). Western blot analyses demonstrated actin-vitamin D binding protein complexes in the blood, which cleared by day 21-28. Our data support modulation of cytokine secretion and macrophage phenotype by vitamin D binding protein later after transplant. Taken together, our data identify an association between filamentous-actin, a mediator of endothelial damage, and vitamin D binding protein, an actin scavenger, as modifiers of risk of clinical consequences of endothelial injury. |
| Databáze: | OpenAIRE |
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