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 AnxA1(hi)CD62L(lo)CD11b(hi) phenotype, whereas week 1 neutrophils were AnxA1(hi)CD62L(lo)CD11b(lo) and displayed minimal adhesion to endothelial monolayers under flow, and week 24 (i.e., lowest glucocorticoid dose) neutrophils were AnxA1(hi)CD62L(hi)CD11b(hi) 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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Nadkarni S,Dalli J,Hollywood J,Mason JC,Dasgupta B,Perretti Mdoi
10.1161/CIRCRESAHA.114.301374subject
Has Abstractpub_date
2014-01-17 00:00:00pages
242-8issue
2eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.114.301374journal_volume
114pub_type
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