88. Role of Neutrophil Extracellular Trap Formation in Systemic Vasculitides
Creators: name: Michailidou1, Despina
name: Kuley1, Runa
name: Mustelin1, Tomas
name: Cuthbertson2, David
name: Grayson3, Peter C.
name: Khalidi4, Nader A.
name: Curry L.  Koening5
name: Langford6, Carol A.
name: McAlear7, Carol A.
name: Moreland8, Larry W.
name: Pagnoux9, Christian
name: Seo10, Philip
name: Specks11, Ulrich
name: Sreih7, Antoine G.
name: Warrington12, Kenneth
name: Monach13, Paul A.
name: Merkel7, Peter A.
name: Lood1, Christian
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Neutrophil extracellular trap (NET) formation, the release of decondensed chromatin and granular proteins from activated neutrophils, is essential in innate immunity. NET formation plays also an important role in autoimmune diseases, including anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a disease that affects small blood vessels. Whether NET formation and autoimmunity against NET antigens such as extracellular histones, a common autoantigen in other autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, occurs in Takayasu’s arteritis (TAK) and giant cell arteritis (GCA), two forof large vessel vasculitis (LVV) is unknown. The objective of this study was to compare levels of NET formation and anti-histone antibodies in AAV and LVV. <strong>Methods:</strong> NETs (neutrophil elastase (NE)-DNA complexes) and anti-histone antibodies were analyzed in plasma samples of healthy controls (n=30), and patients with AAV (granulomatosis with polyangiitis (GPA, n=196), microscopic polyangiitis (MPA, n=74)), TAK (n=66), and GCA (n=82), at times of remission or flare. Physician global assessment (PGA) was used for evaluation of disease activity. <strong>Results:</strong> NE-DNA complexes were significantly elevated in the plasma of patients with AAV and LVV, both at flare and remission, compared to healthy controls (HC), except for patients with MPA at remission (Figure 1A). In patients with TAK, but none of the other conditions, NE-DNA complexes were significantly elevated at time of flare as compared to remission (p&lt;0.05), and NE-DNA levels correlated with PGA (r=0.28, p&lt;0.05). Levels of NETs did not correlate with markers of general inflammation, such as C-reactive protein. Only patients with TAK had significantly higher levels of anti-histone antibodies in their circulation regardless of disease activity (p&lt;0.01) (Figure 1B). In patients with TAK, presence of NETs correlated with levels of anti-histone antibodies (r=0.35, p&lt;0.01). <strong>Conclusions:</strong> NETs, as assessed by NE-DNA complexes, are elevated in both AAV and LVV suggesting a potential common disease link in vasculitides. Presence of anti-histone antibodies in TAK suggests that NETs may be a source of autoantigens in this disease. Further studies are required to explore the role of NETs and anti-histone antibodies in the pathogenesis of vasculitides. <strong>Disclosures:</strong> None <strong>Figure 1.</strong> Levels of NE-DNA complexes and anti-histone antibodies in patients with vasculitis. Levels of A) NE-DNA complexes and B) anti-histone antibodies were analyzed in healthy controls (HC), and patients with vasculitis at times of remission (rem) and active disease. Statistical analyses were done by Mann-Whitney U test with *p&lt;0.05, **p&lt;0.01 and ***p&lt;0.001. Unless otherwise indicated, all analyses are compared to healthy controls. Each circle represents an individual sample, with the bar representing the median of the group. GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; TAK: Takayasu’s arteritis; GCA: giant cell arteritis. B. A.