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What Is ANCA - Vasculitis UK
What Is ANCA - Vasculitis UK
ANCA-associated vasculitis
If a patient has ANCA-associated vasculitis, he or she may have one of three different
vasculitis conditions: 1. granulomatosis with polyangiitis (GPA), previously known as
Wegener’s granulomatosis, 2. Microscopic polyangiitis (MPA) and 3. eosinophilic
granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome (1).
These three conditions are grouped together under the umbrella term ‘ANCA-associated
vasculitis’ because they are all associated with a key protein factor in the blood called ‘ANCA’
and because they all cause in ammation or damage to small blood vessels. Small blood
vessels are found all over the human body, so any part of the body can be affected, but most
commonly the kidneys, lungs, joints, ears, nose, and nerves. Because the kidneys and lungs
are vital organs, early treatment for ANCA-associated vasculitis is very important to prevent
serious organ damage.
ANCA are not only a measureable blood marker in patients with ANCA-associated vasculitis
but they are harmful autoantibodies that are directly involved in small blood vessel damage.
The binding of ANCA to neutrophils in the blood, results in: 1 the release of toxic substances
from neutrophils causing damage to small blood vessel walls, 2 neutrophil migration through
blood vessel walls causing in ammation in surrounding tissues, 3 release of signalling factors
that attract more neutrophils, perpetuating the in ammation and destruction of small blood
vessels (4). ANCA alone are capable of causing vasculitis, as observed in a baby who
developed lung and kidney vasculitis after birth, because MPO-ANCA had crossed the
placenta from the mother(14). Furthermore, medications including propylthiouracil,
hydralazine and penicillamine have been associated with the development of ANCA and
vasculitis. Stopping the medication usually results in clinical improvement and the
disappearance of ANCA from blood (13).
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Figure 1. Diagram showing ANCA-induced ‘activation’ of neutrophils causing in ammation of the blood vessel wall
ANCA testing
ANCA blood tests are performed by two methods: Indirect Immuno uorescence (IIF) and
Enzyme-Linked Immunosorbant Assay (ELISA). Indirect immuno uorescence identi es
ANCA by staining patterns withn neutrophils. ANCA staining throughout the neutrophil
cytoplasm (C-ANCA pattern) usually occurs with a PR3-ANCA. Staining around the cell
nucleus (perinuclear pattern) usually occurs with MPO-ANCA. Immuno uorescence testing
provides a positive or negative result. Conversely ELISA is a technique that allows the level of
PR3 or MPO-ANCA to be measured. Historically, immuno uorescence has been used to
screen patients for ANCA, followed by ELISA to measure the amount of PR3-ANCA or MPO-
ANCA present(17).
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Figure 2. Indirect immuno uorescence of ANCA
After a diagnosis of ANCA-associated vasculitis has been made, regular blood testing for
ANCA is part of routine clinical care. Importantly patients with PR3-ANCA at diagnosis have
a higher long term relapse risk (50% relapse at 5 years) compared to those with MPO-ANCA
at diagnosis (20-30% relapse risk at 5 years). Typically both PR3-ANCA and MPO-ANCA
levels fall during treatment, and most but not all patients become ANCA negative over many
months. ANCA testing can be very helpful for some individual patients for predicting the
timing of a relapse, with a switch from ANCA negative to ANCA positive or a rise in ANCA
level predicting relapse. However, these rules do not consistently apply to all patients,
making the interpretation of ANCA results less straightforward. For example a minority of
patients suffer relapses when they are ANCA negative, and others relapse without a
signi cant rise in their ANCA level. ANCA tests results are therefore always interpreted
along side clinical assessment and other blood test results such as in ammatory markers
(CRP, ESR), kidney function and urine measurements for blood and protein.
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