title: Investigational analysis reveals a potential role for neutrophils in giant-cell arteritis disease progression.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: From the William Harvey Research Institute, Barts, and the London School of Medicine, London, United Kingdom (S.N., J.D., M.P.); Department of Rheumatology, Southend University Hospital, Essex, United Kingdom (J.H., B.D.); and Vascular Science Section, National Heart and Lung Institute, Imperial College, Hammersmith Hospital, London, United Kingdom (J.C.M.).
authors.forename: Suchita
authors.initials: S
authors.lastname: Nadkarni
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.forename: Jane
authors.initials: J
authors.lastname: Hollywood
authors.forename: Justin C
authors.initials: JC
authors.lastname: Mason
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Dasgupta
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000328:Adult; D000368:Aged; D017305:Annexin A1 / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D039481:CD11b Antigen / Q000097:blood; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D013700:Giant Cell Arteritis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D005938:Glucocorticoids / Q000008:administration & dosage; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D018836:Inflammation Mediators / Q000097:blood; D019041:L-Selectin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000145:classification / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D039481:CD11b Antigen; D016207:Cytokines; D005938:Glucocorticoids; C509295:ITGAM protein, human; D018836:Inflammation Mediators; C546935:SELL protein, human; D019041:L-Selectin
keywords: T-lymphocytes; giant-cell arteritis; neutrophils