Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis
Abstract 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 health...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02849-z |
| _version_ | 1818470873056673792 |
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| author | Despina Michailidou Bhargavi Duvvuri Runa Kuley David Cuthbertson Peter C. Grayson 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 Tomas Mustelin Paul A. Monach Peter A. Merkel Christian Lood |
| author_facet | Despina Michailidou Bhargavi Duvvuri Runa Kuley David Cuthbertson Peter C. Grayson 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 Tomas Mustelin Paul A. Monach Peter A. Merkel Christian Lood |
| author_sort | Despina Michailidou |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T21:43:15Z |
| format | Article |
| id | doaj.art-4d4ff93e6b7146b1804cbd57bf2f0bc4 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-13T21:43:15Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-4d4ff93e6b7146b1804cbd57bf2f0bc42022-12-22T02:28:40ZengBMCArthritis Research & Therapy1478-63622022-06-0124111010.1186/s13075-022-02849-zNeutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitisDespina Michailidou0Bhargavi Duvvuri1Runa Kuley2David Cuthbertson3Peter C. Grayson4Nader A. Khalidi5Curry L. Koening6Carol A. Langford7Carol A. McAlear8Larry W. Moreland9Christian Pagnoux10Philip Seo11Ulrich Specks12Antoine G. Sreih13Kenneth J. Warrington14Tomas Mustelin15Paul A. Monach16Peter A. Merkel17Christian Lood18Division of Rheumatology, Department of Medicine, University of WashingtonDivision of Rheumatology, Department of Medicine, University of WashingtonDivision of Rheumatology, Department of Medicine, University of WashingtonHealth Informatics Institute, University of South FloridaSystemic Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin DiseasesDivision of Rheumatology, Mc Master UniversityDivision of Rheumatology, University of UtahDivision of Rheumatology, Cleveland ClinicDivision of Rheumatology, University of PennsylvaniaDivision of Rheumatology and Clinical Immunology, University of ColoradoDivision of Rheumatology, Mount Sinai HospitalDivision of Rheumatology, Johns Hopkins UniversityDivision of Pulmonary and Critical Care Medicine, Mayo ClinicDivision of Rheumatology, University of PennsylvaniaDivision of Rheumatology, Mayo ClinicDivision of Rheumatology, Department of Medicine, University of WashingtonDivision of Rheumatology, Brigham and Women’s HospitalDivision of Rheumatology, University of PennsylvaniaDivision of Rheumatology, Department of Medicine, University of WashingtonAbstract 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.https://doi.org/10.1186/s13075-022-02849-zAnti-neutrophil cytoplasmic antibody-associated vasculitisLarge-vessel vasculitisNeutrophilsMitochondriaFormyl peptide receptor 1 |
| spellingShingle | Despina Michailidou Bhargavi Duvvuri Runa Kuley David Cuthbertson Peter C. Grayson 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 Tomas Mustelin Paul A. Monach Peter A. Merkel Christian Lood Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis Arthritis Research & Therapy Anti-neutrophil cytoplasmic antibody-associated vasculitis Large-vessel vasculitis Neutrophils Mitochondria Formyl peptide receptor 1 |
| title | Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis |
| title_full | Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis |
| title_fullStr | Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis |
| title_full_unstemmed | Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis |
| title_short | Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis |
| title_sort | neutrophil activation in patients with anti neutrophil cytoplasmic autoantibody associated vasculitis and large vessel vasculitis |
| topic | Anti-neutrophil cytoplasmic antibody-associated vasculitis Large-vessel vasculitis Neutrophils Mitochondria Formyl peptide receptor 1 |
| url | https://doi.org/10.1186/s13075-022-02849-z |
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