Oxygen gradient ektacytometry-derived biomarkers are associated with acute complications in sickle cell disease.

Autor:	Rab MAE; Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.; Department of Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Kanne CK; Department of Pediatrics Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA., Boisson C; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France., Bos J; Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., van Oirschot BA; Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Houwing ME; Department of Pediatric Hematology and Oncology, Erasmus Medical Center Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands., Renoux C; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France.; Laboratory of Biochemistry and Molecular Biology, UF Biochemistry of Red Blood Cell Diseases, Est Center of Biology and Pathology, Hospices Civils de Lyon, Lyon, France., Bartels M; Van Creveldkliniek, Divison of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Rijneveld AW; Department of Hematology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands., Nur E; Department of Hematology, Amsterdam University Medical Center, The Netherlands., Cnossen MH; Department of Pediatric Hematology and Oncology, Erasmus Medical Center Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands., Joly P; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France.; Laboratory of Biochemistry and Molecular Biology, UF Biochemistry of Red Blood Cell Diseases, Est Center of Biology and Pathology, Hospices Civils de Lyon, Lyon, France., Nader E; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France., Fort R; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France.; Department of Internal Medicine, Hospices Civils de Lyon, Lyon, France., Connes P; Laboratory LIBM EA7424, University of Lyon 1, 'Vascular Biology and Red Blood Cell' team, Lyon, France.; Laboratory of Excellence GR-Ex, Paris, France., van Wijk R; Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Sheehan VA; Department of Pediatrics Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA., van Beers EJ; Van Creveldkliniek, Divison of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jan 23; Vol. 8 (2), pp. 276-286.
DOI:	10.1182/bloodadvances.2023011013
Abstrakt:	Abstract: We investigated the potential of the point of sickling (PoS; the pO2 tension at which red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease-related complications in 177 children and 50 adults. In the pediatric cohort, for every 10 mmHg increase in PoS reflecting a greater likelihood of sickling, the likelihood of an individual experiencing >1 type of acute complication increased; the adjusted odds ratio (aOR) was 1.65. For every 0.1 increase in minimum elongation index (EImin; reflecting improved red blood cell deformability at hypoxia), the aOR was 0.50. In the adult cohort, for every 10 mmHg increase in PoS, we found an aOR of 3.00, although this was not significant after correcting for multiple testing. There was a trend for an association between higher PoS and greater likelihood of vaso-occlusive episodes (VOEs; children aOR, 1.35; adults aOR, 2.22). In children, only EImin was associated with VOEs (aOR, 0.68). When data of both cohorts were pooled, significant associations with PoS and/or EImin were found for all acute complications, independently and when >1 type of acute complication was assessed. These findings indicate that oxygen gradient ektacytometry generates novel biomarkers and provides a rationale for further development of these biomarkers in the assessment of clinical severity, evaluation of novel therapies, and as surrogate clinical trial end points. These biomarkers may be useful in assessing efficacy of novel therapies like pyruvate kinase activators, voxelotor, and L-glutamine. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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