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Pathophysiology of ANCA-associated Vasculitis

Al-Hussain, Turki MD*; Hussein, Maged H. MD, FACP; Conca, Walter MD, FACP; Al Mana, Hadeel MD*; Akhtar, Mohammed MD, FCAP, FRCPA, FRCPath*

Advances In Anatomic Pathology: July 2017 - Volume 24 - Issue 4 - p 226–234
doi: 10.1097/PAP.0000000000000154
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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules. The propensity to develop these antibodies depends on a variety of predisposing factors such as microbial infection, genetic factors, environmental agents, and therapeutic drugs among others. These factors are usually associated with production of proinflammatory cytokines with capacity to prime the neutrophils. As a result a high proportion of neutrophils in circulation may be primed resulting in exposure of cytoplasmic proteins including myeloperoxidase and proteinase 3 on the surface of the neutrophils. Primed neutrophils are activated by interaction with ANCA in circulation. Activated neutrophils attach to and transmigrate through endothelium and accumulate within the vessel wall. These neutrophils degranulate and produce reactive oxygen radicals and ultimately die, causing tissue injury. Endothelial injury results in leakage of serum proteins and coagulation factors causing fibrinoid necrosis. B cells produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes with excess of Th17, which perpetuate the inflammatory process.

Departments of *Pathology and Laboratory Medicine

Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia

The authors have no funding or conflicts of interest to disclose.

Reprints: Mohammed Akhtar, MD, FCAP, FRCPA, FRCPath, Department of Pathology and Laboratory Medicine (MBC 10), King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Kingdom of Saudi Arabia (e-mails: makhtar69@kfshrc.edu.sa and dr.mohammed.akhtar@gmail.com).

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