Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis

• Published in: Arthritis research & therapy Vol. 24; no. 1; pp. 1 - 160
• Main Authors: Michailidou, Despina, Duvvuri, Bhargavi, Kuley, Runa, Cuthbertson, David, Grayson, Peter C, Khalidi, Nader A, Koening, Curry L, Langford, Carol A, McAlear, Carol A, Moreland, Larry W, Pagnoux, Christian, Seo, Philip, Specks, Ulrich, Sreih, Antoine G, Warrington, Kenneth J, Mustelin, Tomas, Monach, Paul A, Merkel, Peter A, Lood, Christian
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 29.06.2022; BioMed Central; BMC
• Subjects: Age; Anti-neutrophil cytoplasmic antibody-associated vasculitis; Antibodies; Arthritis; Autoantibodies; Care and treatment; Creatinine; Development and progression; Disease; Formyl peptide receptor 1; Health aspects; Inflammation; Large-vessel vasculitis; Mitochondria; Neutrophils; Pathogenesis; Peptides; Plasma; Remission (Medicine); Tumor necrosis factor-TNF; Vasculitis; Vein & artery diseases; United States; United States > US
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-022-02849-z

Objective To assess markers of neutrophil activation such as calprotectin and N-formyl methionine (fMET) in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and large-vessel vasculitis (LVV). Methods Levels of fMET, and calprotectin, were measured in the plasma of healthy controls (n=30) and patients with AAV (granulomatosis with polyangiitis (GPA, n=123), microscopic polyangiitis (MPA, n=61)), and LVV (Takayasu's arteritis (TAK, n=58), giant cell arteritis (GCA, n=68)), at times of remission or flare. Disease activity was assessed by physician global assessment. In vitro neutrophil activation assays were performed in the presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporine H. Results Levels of calprotectin, and fMET were elevated in patients with vasculitis as compared to healthy individuals. Levels of fMET correlated with markers of systemic inflammation: C-reactive protein (r=0.82, p<0.0001), and erythrocyte sedimentation rate (r=0.235, p<0.0001). The neutrophil activation marker, calprotectin was not associated with disease activity. Circulating levels of fMET were associated with neutrophil activation (p<0.01) and were able to induce de novo neutrophil activation via FPR1-mediated signaling. Conclusion Circulating fMET appears to propagate neutrophil activation in AAV and LVV. Inhibition of fMET-mediated FPR1 signaling could be a novel therapeutic intervention for systemic vasculitides. Keywords: Anti-neutrophil cytoplasmic antibody-associated vasculitis, Large-vessel vasculitis, Neutrophils, Mitochondria, Formyl peptide receptor 1