What is the pathophysiology of antibody-mediated vasculitides?

Updated: Dec 10, 2018
  • Author: Nadia Jennifer Chiara Luca, MD; Chief Editor: Lawrence K Jung, MD  more...
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A review by Jennette and Falk discusses the scientific evidence showing that ANCA immunoglobulin Gs (IgGs) are involved in the pathogenesis of small vessel vasculitides such as GPA and MPA. [12]

ANCA antibodies are directed towards cytoplasmic proteins within neutrophils and monocytes (eg, PR3, MPO), which may also be expressed at the cell surface, particularly on stimulated cells. In vitro studies have shown that ANCA IgGs can directly activate neutrophils and monocytes by both Fc receptor engagement and direct Fab2 binding to antigen. These activated cells interact with endothelial cells via adhesion molecules and release inflammatory mediators, such as toxic granule enzymes and reactive oxygen metabolites that cause apoptosis and necrosis. In addition, anti-MPO IgG may activate MPO itself triggering an oxidative burst and resulting in severe endothelial damage. ANCA-activated neutrophils may release factors that activate the alternative complement pathway, which initiates an amplification loop that mediates the severe necrotizing inflammation of ANCA disease. [12]

In vivo studies also support this pathogenesis; for example, injection of mice with anti-MPO antibodies results in the development of necrotizing and crescentic glomerulonephritis and pulmonary capillaritis. [13]

A study that sought to assess clinical and B cell biomarkers to predict relapse after rituximab in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using retreatment on clinical relapse strategy found that naïve B-lymphopenia may be a biomarker of disease activity in AAV. [14, 15]

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