Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis

Despina Michailidou, Runa Kuley, Ting Wang, Payton Hermanson, Peter C. Grayson, David Cuthbertson, Nader A. Khalidi, Curry L. Koening, Carol A. Langford, Carol A. McAlear, Larry W. Moreland, Christian Pagnoux, Philip Seo, Ulrich Specks, Antoine G. Sreih, Kenneth J. Warrington, Paul A. Monach, Peter A. Merkel, Christian Lood

Research output: Contribution to journalArticlepeer-review

Abstract

Levels of neutrophil extracellular traps (NETs) were measured in plasma of healthy controls (HC, n = 30) and patients with granulomatosis with polyangiitis (GPA, n = 123), microscopic polyangiitis (MPA, n = 61), Takayasu's arteritis (TAK, n = 58), and giant cell arteritis (GCA, n = 68), at times of remission or activity and correlated with levels of the platelet-derived thrombospondin-1 (TSP-1). Levels of NETs were elevated during active disease in patients with GPA (p < 0.0001), MPA (p = 0.0038), TAK (p < 0.0001), and GCA (p < 0.0001), and in remission for GPA, p < 0.0001, MPA, p = 0.005, TAK, p = 0.03, and GCA, p = 0.0009. All cohorts demonstrated impaired NET degradation. Patients with GPA (p = 0.0045) and MPA (p = 0.005) had anti-NET IgG antibodies. Patients with TAK had anti-histone antibodies (p < 0.01), correlating with presence of NETs. Levels of TSP-1 were increased in all patients with vasculitis, and associated with NET formation. NET formation is a common process in vasculitides. Targeting NET formation or degradation could be potential therapeutic approaches for vasculitides.

Original languageEnglish (US)
Article number109274
JournalClinical Immunology
Volume249
DOIs
StatePublished - Apr 2023
Externally publishedYes

Keywords

  • Anti-neutrophil cytoplasmic antibody associated vasculitis
  • Histone
  • Large vessel vasculitis
  • Neutrophil extracellular traps
  • Neutrophils
  • Platelet activation
  • Thrombospondin-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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