TY - JOUR
T1 - Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis
AU - Michailidou, Despina
AU - Duvvuri, Bhargavi
AU - Kuley, Runa
AU - Cuthbertson, David
AU - Grayson, Peter C.
AU - Khalidi, Nader A.
AU - Koening, Curry L.
AU - Langford, Carol A.
AU - McAlear, Carol A.
AU - Moreland, Larry W.
AU - Pagnoux, Christian
AU - Seo, Philip
AU - Specks, Ulrich
AU - Sreih, Antoine G.
AU - Warrington, Kenneth J.
AU - Mustelin, Tomas
AU - Monach, Paul A.
AU - Merkel, Peter A.
AU - Lood, Christian
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Anti-neutrophil cytoplasmic antibody-associated vasculitis
KW - Formyl peptide receptor 1
KW - Large-vessel vasculitis
KW - Mitochondria
KW - Neutrophils
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U2 - 10.1186/s13075-022-02849-z
DO - 10.1186/s13075-022-02849-z
M3 - Article
C2 - 35768848
AN - SCOPUS:85133120571
SN - 1478-6354
VL - 24
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 160
ER -