Expanded population of low-density neutrophils in juvenile idiopathic arthritis

IntroductionJuvenile idiopathic arthritis (JIA), a clinically variable disease characterized by autoimmune arthritis, affects children, and its immunopathology remains elusive. Alterations in neutrophil biology play an important role in this disease. In the present study, we aimed to explore the fea...

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Main Authors: Zuzana Parackova, Irena Zentsova, Marketa Bloomfield, Adam Klocperk, Rudolf Horvath, Hana Malcova, Dita Cebecauerova, Anna Sediva
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229520/full
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author Zuzana Parackova
Irena Zentsova
Marketa Bloomfield
Adam Klocperk
Rudolf Horvath
Hana Malcova
Dita Cebecauerova
Anna Sediva
author_facet Zuzana Parackova
Irena Zentsova
Marketa Bloomfield
Adam Klocperk
Rudolf Horvath
Hana Malcova
Dita Cebecauerova
Anna Sediva
author_sort Zuzana Parackova
collection DOAJ
description IntroductionJuvenile idiopathic arthritis (JIA), a clinically variable disease characterized by autoimmune arthritis, affects children, and its immunopathology remains elusive. Alterations in neutrophil biology play an important role in this disease. In the present study, we aimed to explore the features of low-density neutrophils (LDNs) in patients with JIA.MethodsGene expression of peripheral blood mononuclear cells (PBMCs) from children with distinct subtypes of JIA was analyzed by NanoString Immunology panel. Presence of LDNs was ascertained by flow cytometry and the release of neutrophil-associated products were analyzed by LUMINEX.ResultsLDNs were detected in patients’ peripheral blood mononuclear cells (PBMCs) after density gradient centrifugation. Transcriptomic analysis of JIA PBMCs revealed that genes related to neutrophil degranulation were markedly upregulated. The number of LDNs and level of their degranulation products increased in patients’ PBMCs and correlated with serum calprotectin, but not with disease activity, sedimentation rate and C-reactive protein (CRP) levels. The phenotypes of LDNs varied from those of normal-density neutrophils and healthy donor LDNs. Phenotypical analysis revealed LDNs are immature and primed population with decreased suppressive capacity. A negative correlation between surface proteins CD62L, CD66b, and CD11b and the number of inflamed joints/JADAS was established.ConclusionOur results describe LDNs as primed, degranulated, immature cells with impaired suppressive activities. This work thus contributes to the increasing body of evidence that LDNs in JIA are altered and their role in the disease immunopathogenesis and possible clinical associations should be investigated further.
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spelling doaj.art-3c1ff646c020478199aeb355809d1dc22023-10-17T06:21:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12295201229520Expanded population of low-density neutrophils in juvenile idiopathic arthritisZuzana Parackova0Irena Zentsova1Marketa Bloomfield2Adam Klocperk3Rudolf Horvath4Hana Malcova5Dita Cebecauerova6Anna Sediva7Department of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, CzechiaDepartment of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, CzechiaDepartment of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, CzechiaDepartment of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, CzechiaDepartment of Paediatric and Adult Rheumatology, University Hospital in Motol, Prague, CzechiaDepartment of Paediatric and Adult Rheumatology, University Hospital in Motol, Prague, CzechiaDepartment of Paediatric and Adult Rheumatology, University Hospital in Motol, Prague, CzechiaDepartment of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, CzechiaIntroductionJuvenile idiopathic arthritis (JIA), a clinically variable disease characterized by autoimmune arthritis, affects children, and its immunopathology remains elusive. Alterations in neutrophil biology play an important role in this disease. In the present study, we aimed to explore the features of low-density neutrophils (LDNs) in patients with JIA.MethodsGene expression of peripheral blood mononuclear cells (PBMCs) from children with distinct subtypes of JIA was analyzed by NanoString Immunology panel. Presence of LDNs was ascertained by flow cytometry and the release of neutrophil-associated products were analyzed by LUMINEX.ResultsLDNs were detected in patients’ peripheral blood mononuclear cells (PBMCs) after density gradient centrifugation. Transcriptomic analysis of JIA PBMCs revealed that genes related to neutrophil degranulation were markedly upregulated. The number of LDNs and level of their degranulation products increased in patients’ PBMCs and correlated with serum calprotectin, but not with disease activity, sedimentation rate and C-reactive protein (CRP) levels. The phenotypes of LDNs varied from those of normal-density neutrophils and healthy donor LDNs. Phenotypical analysis revealed LDNs are immature and primed population with decreased suppressive capacity. A negative correlation between surface proteins CD62L, CD66b, and CD11b and the number of inflamed joints/JADAS was established.ConclusionOur results describe LDNs as primed, degranulated, immature cells with impaired suppressive activities. This work thus contributes to the increasing body of evidence that LDNs in JIA are altered and their role in the disease immunopathogenesis and possible clinical associations should be investigated further.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229520/fulljuvenile idiopathic arthritisneutrophilslow-density neutrophilscalprotectinactivationreverse transmigration
spellingShingle Zuzana Parackova
Irena Zentsova
Marketa Bloomfield
Adam Klocperk
Rudolf Horvath
Hana Malcova
Dita Cebecauerova
Anna Sediva
Expanded population of low-density neutrophils in juvenile idiopathic arthritis
Frontiers in Immunology
juvenile idiopathic arthritis
neutrophils
low-density neutrophils
calprotectin
activation
reverse transmigration
title Expanded population of low-density neutrophils in juvenile idiopathic arthritis
title_full Expanded population of low-density neutrophils in juvenile idiopathic arthritis
title_fullStr Expanded population of low-density neutrophils in juvenile idiopathic arthritis
title_full_unstemmed Expanded population of low-density neutrophils in juvenile idiopathic arthritis
title_short Expanded population of low-density neutrophils in juvenile idiopathic arthritis
title_sort expanded population of low density neutrophils in juvenile idiopathic arthritis
topic juvenile idiopathic arthritis
neutrophils
low-density neutrophils
calprotectin
activation
reverse transmigration
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229520/full
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