Pathogenesis and pathology of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis

Abstract

•AAV is characterized by necrotizing small vessel vasculitis with positive serum ANCA.•MPO/PR3-ANCA and neutrophils play central roles in AAV pathogenicity.•Dysregulated complement system primes neutrophils.•MPO-ANCA directly activates neutrophils to induce NETosis followed by releasing NETs.•B cells, T cells, and dendritic cells also contribute to the pathogenicity of AAV.

Keywords: ANCA-Associated vasculitis; Anti-neutrophil cytoplasmic antibody; NETs; Neutrophil.

Fig. 1

The mechanism of ANCA production and small-vessel vasculitis [76]. Microorganisms are either captured by dendritic cells or activate the alternative complement pathway. Dendritic cells lead macrophages to release inflammatory cytokines through antigen presentation to T cells. The alternative pathway produces C5a, which stabilizes the C3(H₂O)Bb complex. Inflammatory cytokines or C5a stimulate neutrophils to express MPO and PR3 on their membrane [[77], [78], [79]]. Fab of ANCA binds them, while Fc of ANCA binds with the Fc receptor on neutrophils, which results in the release of ROS, lytic enzymes, and NETs that eventually cause vascular endothelial damage [70].

Fig. 2

Theory of autoantigen complementarity [13,14]. When a complementary peptide, which is antisense to the autoantigen, is produced, or an antisense peptide mimic invades the body, the immune system produces an idiotypic antibody for the complementary peptide or mimic. Following this, an anti-idiotypic antibody is produced and cross-reacts with the autoantigen epitopes.