An Investigational Analysis Reveals a Potential Role for Neutrophils in Giant-Cell Arteritis Disease Progression
Rationale: Giant-cell arteritis (GCA) is a large vessel vasculitis characterized by immune cell infiltration, yet the potential involvement of neutrophils has been rarely 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 over a 6-month period.
Methods and Results: Blood samples were taken within 48h of therapy commencement and at week-1, 4 and 24 post-glucocorticoid. Flow-cytometric analysis revealed three distinct neutrophils populations and phenotypes. Within 48hrs 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 (i.e. lowest glucocorticoid dose) neutrophils were AnxA1hiCD62LhiCD11bhi with increased endothelial adhesion under flow. Week 24 plasma analyses showed high levels of CXCL5, IL-8, IL-17 and IL-6. Importantly, comparison of week-1 and 24 samples revealed a suppressive neutrophil effect on T-cell proliferation at the former time point only. Finally, in vitro incubation of naïve neutrophils with concentrations of IL-6 and IL-17 quantified in GCA plasma at week-1 and 24 replicated this differential modulation of lymphocyte proliferation.
Conclusions: This translational study highlights a novel clinical manifestations of GCA, with evidence for a neutrophil component and an 'escaped' pro-inflammatory phenotype when glucocorticoid therapy is tapered. These results indicate potential involvement of neutrophils in GCA pathogenesis.
- Giant Cell Arteritis
- T lymphocytes
- Disease Progression
- polymorphonuclear leukocyte adhesion
- polymorphonuclear neutrophils activation blood cells
- Received March 14, 2013.
- Revision received October 21, 2013.
- Accepted October 21, 2013.