ANCA = anti-neutrophil cytoplasmic antibody; GPA = granulomatosis with polyangiitis; MPA = microscopic polyangiitis.
The role of the complement pathway in AAV has been historically underappreciated4
Complement activation may amplify inflammation and vascular injury in AAV3,5
Conventional standard therapies address some pathways involved in vascular inflammation, but do not directly address complement6,7
AAV = ANCA-associated vasculitis.
What does a closer look at THE COMPLEMENT PATHWAY REVEAL?
The complement system includes pathogenic mediators in ANCA-associated vasculitis.4 Click or tap each section to learn more.
Loss of tolerance to PR3 and/or MPO leads to activation of T cells and B cells, promoting ANCA production1
The complement pathway leads to the generation of C5a, which can prime neutrophils. Circulating ANCAs bind to PR3 or MPO on the surface of primed neutrophils, triggering their activation3,4
Activated neutrophils adhere to the endothelium and undergo NETosis, releasing destructive mediators and amplifying complement activation through C5a generation1-3
C5a works as a chemoattractant, binding to C5aRs to draw more neutrophils to the site of inflammation. This perpetuates the priming and activation of neutrophils, which can lead to endothelial injury and impact to organs2-4,8
C5a = complement fragment 5a; C5aR = C5a receptor; MPO = myeloperoxidase; NET = neutrophil extracellular traps; PR3 = proteinase 3.
Could understanding the multiple pathways involved in ANCA-associated vasculitis help with your treatment approach?
ANCA-associated vasculitis involves:
- Multiple immune pathways contributing to inflammation1-3
- Inflammatory amplification mediated by the complement pathway1,3,4
- A broader inflammatory network beyond humoral immunity alone3-5,8
KEEP EXPLORING:
Vasculitis Foundation
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References: 1. Kitching AR, Anders H-J, Basu N, et al. Nat Rev Dis Primers. 2020;6(1):71. 2. Shochet L, Holdsworth S, Kitching AR. Front Immunol. 2020;11:525. 3. Chen M, Jayne DRW, Zhao M-H. Nat Rev Nephrol. 2017;13(6):359-367. 4. Marvisi C, Ricordi C, Catellani C, et al. Front Immunol. 2025;16:1616837. 5. Kimoto Y, Horiuchi T. Front Immunol. 2022;13:926044. 6. Jones RB, Ferraro AJ, Chaudhry AN, et al. Arthritis Rheum. 2009;60(7):2156-2168. 7. Winkelstein A. Blood. 1973;41(2):273-284. 8. Al-Hussain T, Hussein MH, Conca W, et al. Adv Anat Pathol. 2017;24(4):226-234.
