Neutrophils in ANCA-associated vasculitis: Mechanisms and implications for management

Area of Science:

• Immunology
• Rheumatology
• Pathology

Background:

• Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises systemic autoimmune diseases characterized by small vessel inflammation.
• Key subtypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
• Neutrophil function is central to AAV pathogenesis, involving both innate and adaptive immunity.

Purpose of the Study:

• To elucidate the intricate mechanisms linking neutrophils to diverse AAV subtypes.
• To highlight recent discoveries regarding neutrophil-immune interactions in AAV.
• To discuss signaling pathways regulating neutrophils in AAV.

Main Methods:

• This review synthesizes current literature on neutrophil involvement in AAV.
• It examines the roles of neutrophil proteins (e.g., MPO, PR3) and neutrophil extracellular traps (NETs).
• The review analyzes complement pathway activation and respiratory burst in AAV pathogenesis.

Main Results:

• Neutrophil proteins like myeloperoxidase (MPO) and proteinase 3 (PR3) trigger adaptive immunity, producing MPO-ANCA and PR3-ANCA.
• Neutrophil extracellular trap (NET) formation, complement activation, and respiratory burst contribute to vascular inflammation.
• Specific signaling pathways governing neutrophil behavior in AAV are identified.

Conclusions:

• Neutrophil dysregulation is a critical factor in the development and progression of AAV.
• Further research into these neutrophil-mediated pathways may reveal novel biomarkers.
• Targeting neutrophil functions presents a promising strategy for future AAV therapies.