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Abstract: SA-OR025

Induction of Eosinophilic Granulomatosis with Polyangiitis by Myeloperoxidase-ANCA in Mice with Allergic Airway Disease

Session Information

  • ANCA It Is
    November 09, 2019 | Location: 207, Walter E. Washington Convention Center
    Abstract Time: 05:18 PM - 05:30 PM

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Hu, Peiqi, UNC-Chapel Hill, Chapel Hill, North Carolina, United States
  • Xiao, Hong, UNC-Chapel Hill, Chapel Hill, North Carolina, United States
  • Alba, Marco A., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald J., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a phenotype of ANCA vasculitis associated with asthma, and blood and tissue eosinophilia. EGPA is characterized by eosinophil-rich infiltrates, granulomatous inflammation, necrotizing vasculitis and pauci-immune crescentic glomerulonephritis (CGN). We hypothesized that EGPA can be induced by injecting anti-MPO into mice with asthma-like disease.

Methods

Ovalbumin (OVA) or house dust mites (HDM) were used to induce acute allergic airway inflammation in C57Bl6 mice that were injected either intraperitoneally (i.p.) with 20ug OVA on days -21 and -7 and administered intranasally (i.n.) 1% OVA in saline on days 1-5; or administrated 25ug HDM protein i.n. in 20ul PBS for 5 days, followed by 2 days of rest, then repeated for another week, followed by 2 daily HDM doses. Thereafter, mice received 75ug/g body weight anti-MPO IgG i.p. Mice were sacrificed 6 days after anti-MPO injection.

Results

Control mice receiving OVA(n=3) or HDM(n=3) but no anti-MPO developed mild eosinophil-rich pulmonary airway inflammation without pulmonary hemorrhage, granulomatous lesions, or CGN. Mice receiving anti-MPO without OVA or HDM (n=3) developed CGN but no lung lesions. Six days after iv injection of anti-MPO IgG, OVA(n=3) or HDM (n=3) treated mice developed more extensive eosinophil-rich pulmonary inflammation, acute capillaritis with hemorrhage and granulomatous inflammation containing numerous eosinophils with admixed multinucleated giant cells. All mice receiving anti-MPO had similar levels of serum anti-MPO and developed similar CGN severity (avg. crescents with OVA 18.7%, HDM 18.7% and anti-MPO alone 18%); whereas control mice treated with OVA or HDM alone had no CGN.

Conclusion

Mouse models of anti-MPO induced EGPA can be generated in mice with acute allergic airway disease. We hypothesize that respiratory tract neutrophils primed by the allergic airway disease are activated by anti-MPO IgG, and amplify the eosinophil-rich inflammation resulting in pulmonary capillaritis and granulomatosis. These models provide useful tools for studying pathogenesis and therapeutic strategies for EGPA.

Funding

  • NIDDK Support