Investigational Analysis Reveals a Potential Role for Neutrophils in Giant-Cell Arteritis Disease Progression
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Rationale: Giant-cell arteritis (GCA) is a large-vessel vasculitis characterized by immune cell infiltration, yet the potential involvement of neutrophils has rarely been studied.
Objective: We investigated whether alterations in neutrophil reactivity occurred in the pathogenesis of GCA or during its clinical management with a canonical glucocorticoid dose regimen during a 6-month period.
Methods and Results: Blood samples were taken within 48 hours of therapy commencement and at weeks 1, 4, and 24 after glucocorticoid dose. Flow cytometric analysis revealed 3 distinct neutrophil populations and phenotypes. Within 48 hours of steroid treatment, neutrophils displayed an AnxA1hiCD62LloCD11bhi phenotype, whereas week 1 neutrophils were AnxA1hiCD62LloCD11blo and displayed minimal adhesion to endothelial monolayers under flow, and week 24 (ie, lowest glucocorticoid dose) neutrophils were AnxA1hiCD62LhiCD11bhi with increased endothelial adhesion under flow. Week 24 plasma analyses showed high levels of C-X-C motif chemokine ligand 5, interleukin (IL) 8, IL-17, and IL-6. Importantly, comparison of week 1 and week 24 samples revealed a suppressive neutrophil effect on T-cell proliferation at the former time point only. Finally, in vitro incubation of naive neutrophils with concentrations of IL-6 and IL-17 quantified in GCA plasma at weeks 1 and 24 replicated this differential modulation of lymphocyte proliferation.
Conclusions: This translational study highlights a novel clinical manifestation of GCA, with evidence for a neutrophil component and an escaped proinflammatory phenotype when glucocorticoid therapy is tapered. These results indicate potential involvement of neutrophils in GCA pathogenesis.
Objective: We investigated whether alterations in neutrophil reactivity occurred in the pathogenesis of GCA or during its clinical management with a canonical glucocorticoid dose regimen during a 6-month period.
Methods and Results: Blood samples were taken within 48 hours of therapy commencement and at weeks 1, 4, and 24 after glucocorticoid dose. Flow cytometric analysis revealed 3 distinct neutrophil populations and phenotypes. Within 48 hours of steroid treatment, neutrophils displayed an AnxA1hiCD62LloCD11bhi phenotype, whereas week 1 neutrophils were AnxA1hiCD62LloCD11blo and displayed minimal adhesion to endothelial monolayers under flow, and week 24 (ie, lowest glucocorticoid dose) neutrophils were AnxA1hiCD62LhiCD11bhi with increased endothelial adhesion under flow. Week 24 plasma analyses showed high levels of C-X-C motif chemokine ligand 5, interleukin (IL) 8, IL-17, and IL-6. Importantly, comparison of week 1 and week 24 samples revealed a suppressive neutrophil effect on T-cell proliferation at the former time point only. Finally, in vitro incubation of naive neutrophils with concentrations of IL-6 and IL-17 quantified in GCA plasma at weeks 1 and 24 replicated this differential modulation of lymphocyte proliferation.
Conclusions: This translational study highlights a novel clinical manifestation of GCA, with evidence for a neutrophil component and an escaped proinflammatory phenotype when glucocorticoid therapy is tapered. These results indicate potential involvement of neutrophils in GCA pathogenesis.
Date Issued
2014-01-17
Date Acceptance
2013-10-21
Citation
Circulation Research, 2014, 114 (2), pp.242-248
ISSN
1524-4571
Publisher
American Heart Association
Start Page
242
End Page
248
Journal / Book Title
Circulation Research
Volume
114
Issue
2
Copyright Statement
© 2013 American Heart Association, Inc.
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Hematology
Peripheral Vascular Disease
Cardiovascular System & Cardiology
CARDIAC & CARDIOVASCULAR SYSTEMS
HEMATOLOGY
PERIPHERAL VASCULAR DISEASE
giant-cell arteritis
neutrophils
T-lymphocytes
ANNEXIN A1
GLUCOCORTICOIDS
INFLAMMATION
EXPRESSION
RESPONSES
Publication Status
Published