Dynamics of neutrophil phenotype and function in sickle cell disease

IntroductionWhile sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehens...

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Main Authors: Aafke E. Gaartman, Lydian A. de Ligt, Boukje M. Beuger, Anton T. J. Tool, Martijn Veldthuis, Taco W. Kuijpers, Rob van Zwieten, Bart J. Biemond, Robin van Bruggen, Erfan Nur
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591283/full
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author Aafke E. Gaartman
Aafke E. Gaartman
Lydian A. de Ligt
Lydian A. de Ligt
Lydian A. de Ligt
Boukje M. Beuger
Anton T. J. Tool
Martijn Veldthuis
Taco W. Kuijpers
Taco W. Kuijpers
Rob van Zwieten
Bart J. Biemond
Robin van Bruggen
Erfan Nur
Erfan Nur
author_facet Aafke E. Gaartman
Aafke E. Gaartman
Lydian A. de Ligt
Lydian A. de Ligt
Lydian A. de Ligt
Boukje M. Beuger
Anton T. J. Tool
Martijn Veldthuis
Taco W. Kuijpers
Taco W. Kuijpers
Rob van Zwieten
Bart J. Biemond
Robin van Bruggen
Erfan Nur
Erfan Nur
author_sort Aafke E. Gaartman
collection DOAJ
description IntroductionWhile sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehensive exploration of neutrophil characteristics in SCD patients during steady state and vaso-occlusive crisis (VOC), as well as in response to therapeutic interventions.MethodsNeutrophil phenotype was assessed by flow cytometry and functional properties were evaluated by measurement of neutrophil adhesion and reactive oxygen species (ROS) production.ResultsA total of 49 SCD patients (of whom 19 during both steady state and VOC) along with 16 healthy ethnicity-matched and 30 non-matched controls, were included in the study. Differences were observed between neutrophils from patients compared to controls and between control groups. Neutrophil phenotype was more activated in SCD patients compared to non-matched controls. Neutrophil adhesion was increased in steady-state SCD patients compared to both ethnicity-matched and non-matched controls.DiscussionWhile neutrophil phenotype in SCD patients differed from non-matched controls, in contrast to earlier studies, the differences in neutrophil phenotype between SCD patients and ethnicity-matched controls were modest. In vitro neutrophil adhesion was higher in SCD patients than in ethnicity-matched and non-matched controls. Potential explanations for the discrepancies between earlier findings and our study are the large variation in neutrophil phenotypes between individuals, methodological variability between studies and differences in the time interval between blood sample collection and the measurements.
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spelling doaj-art-72b1510491e34bbaaa050b17b76b8cc12025-08-20T01:48:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15912831591283Dynamics of neutrophil phenotype and function in sickle cell diseaseAafke E. Gaartman0Aafke E. Gaartman1Lydian A. de Ligt2Lydian A. de Ligt3Lydian A. de Ligt4Boukje M. Beuger5Anton T. J. Tool6Martijn Veldthuis7Taco W. Kuijpers8Taco W. Kuijpers9Rob van Zwieten10Bart J. Biemond11Robin van Bruggen12Erfan Nur13Erfan Nur14Department of Hematology, Amsterdam University Medical Center, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam University Medical Center, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsDepartment of Pediatric Hematology, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsLaboratory of Red Blood Cell Diagnostics and Iron, Sanquin Diagnostics, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsDepartment of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, NetherlandsLaboratory of Red Blood Cell Diagnostics and Iron, Sanquin Diagnostics, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam University Medical Center, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsDepartment of Hematology, Amsterdam University Medical Center, Amsterdam, NetherlandsRed Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, NetherlandsIntroductionWhile sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehensive exploration of neutrophil characteristics in SCD patients during steady state and vaso-occlusive crisis (VOC), as well as in response to therapeutic interventions.MethodsNeutrophil phenotype was assessed by flow cytometry and functional properties were evaluated by measurement of neutrophil adhesion and reactive oxygen species (ROS) production.ResultsA total of 49 SCD patients (of whom 19 during both steady state and VOC) along with 16 healthy ethnicity-matched and 30 non-matched controls, were included in the study. Differences were observed between neutrophils from patients compared to controls and between control groups. Neutrophil phenotype was more activated in SCD patients compared to non-matched controls. Neutrophil adhesion was increased in steady-state SCD patients compared to both ethnicity-matched and non-matched controls.DiscussionWhile neutrophil phenotype in SCD patients differed from non-matched controls, in contrast to earlier studies, the differences in neutrophil phenotype between SCD patients and ethnicity-matched controls were modest. In vitro neutrophil adhesion was higher in SCD patients than in ethnicity-matched and non-matched controls. Potential explanations for the discrepancies between earlier findings and our study are the large variation in neutrophil phenotypes between individuals, methodological variability between studies and differences in the time interval between blood sample collection and the measurements.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591283/fullsickle cell diseaseneutrophil activationneutrophil adhesionneutrohil agingneutrophil phenotypehemolysis
spellingShingle Aafke E. Gaartman
Aafke E. Gaartman
Lydian A. de Ligt
Lydian A. de Ligt
Lydian A. de Ligt
Boukje M. Beuger
Anton T. J. Tool
Martijn Veldthuis
Taco W. Kuijpers
Taco W. Kuijpers
Rob van Zwieten
Bart J. Biemond
Robin van Bruggen
Erfan Nur
Erfan Nur
Dynamics of neutrophil phenotype and function in sickle cell disease
Frontiers in Immunology
sickle cell disease
neutrophil activation
neutrophil adhesion
neutrohil aging
neutrophil phenotype
hemolysis
title Dynamics of neutrophil phenotype and function in sickle cell disease
title_full Dynamics of neutrophil phenotype and function in sickle cell disease
title_fullStr Dynamics of neutrophil phenotype and function in sickle cell disease
title_full_unstemmed Dynamics of neutrophil phenotype and function in sickle cell disease
title_short Dynamics of neutrophil phenotype and function in sickle cell disease
title_sort dynamics of neutrophil phenotype and function in sickle cell disease
topic sickle cell disease
neutrophil activation
neutrophil adhesion
neutrohil aging
neutrophil phenotype
hemolysis
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591283/full
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