Author:
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
Abstract
AbstractObjectiveTo 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).MethodsLevels 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.ResultsLevels 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.ConclusionCirculating 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.
Funder
NIH
Pfizer US Pharmaceuticals Group grant
National Center for Advancing Translational Sciences
National Center for Research Resources
Publisher
Springer Science and Business Media LLC
Cited by
11 articles.
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