Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation of small blood vessels.
This inflammation is caused by white blood cells called neutrophils that erroneously attack the cells lining blood vessels. In most cases, neutrophils go haywire because patients produce self-reactive antibodies called ANCAs that attach to these immune cells and wrongly activate them.
Since small blood vessels are present nearly all over the body, AAV can cause many different symptoms. For each patient, the symptoms will depend on the organ or tissue involved.
Although scientists understand how AAV damages the body, the factors causing immune system malfunction are largely unknown. Studies point to a combination of genetics and environmental factors, such as exposure to pollutants and certain drugs, as well as microbial infections.
The immune system is designed to defend the body from foreign invaders, such as viruses and bacteria, while leaving its own cells and tissues unharmed. In people with autoimmune conditions, however, immune cells erroneously see the body’s own cells as a threat, and launch an inflammatory attack against them.
As its name implies, ANCA-associated vasculitis is characterized by the presence of autoantibodies — which mistakenly recognize healthy tissue, leading to autoimmunity – named ANCAs, sometimes years before symptoms are evident. These antibodies bind to white blood cells called neutrophils, and trigger an immune reaction against the cells lining blood vessels.
There are two main kinds of ANCA antibodies in people with AAV – those that target the proteinase 3 (PR3) protein on neutrophils and antibodies targeting the protein myeloperoxidase (MPO) – each resulting in distinct disease manifestations.
These antibodies also can be classified according to their localization inside neutrophils. MPO-ANCAs typically are found close to and inside the nucleus (perinuclear ANCAs), while PR3-ANCAs usually are dispersed in the cells’ cytoplasm (cytoplasmic ANCAs).
However, patients also can have antibodies against other proteins, such as lysozyme, cathepsin G, lactoferrin, elastase and azurocidin. These antibodies normally have an “atypical pattern,” meaning they have combinations of both cytoplasmic and perinuclear localizations.
Other rare antibodies are those targeting the bactericidal/permeability-increasing protein, which are common in patients with chronic airway infections, in whom vasculitis may appear.
There is growing evidence that genetics have an important contribution to AAV, potentially in combination with a bacterial or viral infection, but the mechanisms of how these factors may be linked to ANCA vasculitis are not well understood.
The strongest association was observed for the major histocompatibility complex (MHC), a family of genes containing information to produce proteins with a key role in immune response.
An association also has been suggested for mutations in the SERPINA1 gene, which may increase the amount of MPO and PR3 in neutrophils.
There is evidence for the role of silica — a compound present in sand, soil, and rock that stimulates inflammatory reactions — in the development of AAV. Consequently, workers involved in construction jobs are potentially exposed when handling the materials.
Inhalation of chemical compounds used in industry also is a risk factor for AAV. These include alcohols, paint thinners, and glues, among other toxic compounds.
Farming also has been implicated in AAV, namely due to inhaled substances from soil, dusts, animals, and pesticides. Additionally, exposure to environmental dusts, such as those released during natural disasters, may be related to disease development.
Medications can result in ANCA vasculitis, but patients usually have a good prognosis if the disease-causing agent is discontinued immediately. A number of treatments have been linked to the development of AAV, including some used for thyroid disease, rheumatoid diseases, or severe acne.
Prolonged use of cocaine also can trigger the production of ANCA antibodies and result in AAV-like symptoms, including kidney inflammation.
While the mechanisms leading to AAV remains poorly understood for most of these compounds, researchers believe that their powerful epigenetic effects — the ability to change which genes are active and to which extent — are potentially what causes autoimmunity.
Infectious agents, such as viruses and bacteria, also are believed to participate in the development of ANCA vasculitis. However, the exact microorganisms and mechanisms of action remain to be fully elucidated.
Factors related to seasonality — when something changes with the seasons — such as the weather or exposure to ultraviolet (UV) radiation, also may be associated with AAV.
Although AAV can occur at any age, its incidence increases gradually with age until the late 80s. It also is slightly more common in males than females.
Last updated: May 11, 2021
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