To test for certain autoimmune disorders, specifically small vessel vasculitities such as as Granulomatosis with polyangitis (GPA formerly known as Wegners Granulomatosis [WG]), microscopic polyangitis (MPA), Churg-Strauss Syndrome (CSS) and a few others
When your doctor thinks that you have symptoms, such as a “vasculitic” rash or chest/kidney symptoms that may be due to a vascular inflammatory disorder; In patients who are known to have antineutrophil cytoplasmic antibodies (ANCA) associated small vessel vasculitis, ANCA measurement is sometimes used to monitor response to therapy
A blood sample taken from a vein in your arm
Antineutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies produced when a person's immune system mistakenly targets and attacks its own neutrophil proteins. Two of the most commonly targeted proteins are myeloperoxidase (MPO) and proteinase 3 (PR3). This results in the production of antibodies to MPO and/or PR3. The ANCA blood test detects the presence or absence of these autoantibodies by looking at the pattern of fluorescence on a slide under a microscope.
Antineutrophil cytoplasmic antibodies may be present in a variety of autoimmune disorders that cause inflammation and damage to blood vessels, predominantly small blood vessels, throughout the body (systemic vasculitis). Vasculitis can cause tissue and organ damage due to the narrowing and obstruction of these small blood vessels and the subsequent loss of blood supply. It can also produce areas of weakness in blood vessel walls, known as aneurysms, which have the potential to rupture.
The symptoms experienced by a person with small vessel systemic vasculitis depend upon the degree of autoimmune activity and the parts of the body involved. Early in the disease process, symptoms are often nonspecific – they include fatigue, fever, weight loss, muscle aches, and night sweats. As the disorder progresses, vascular damage may affect the functioning of the kidneys, eyes, skin, lungs, and liver. This can cause a wide range of symptoms related to these organ systems.
PR3 antibodies are most frequently seen in Granulomatosis with polyangitis (GPA). MPO antibodies are most often associated with microscopic polyangitis but may also be seen in people with pauci-immune necrotising glomerulonephritis, Churg-Strauss syndrome, and GPA.For more about these conditions, visit the Vasculitis UK.
How is it used?
An ANCA test is requested in order to evaluate someone who has symptoms that may be due to autoimmune vasculitis. It may be requested by itself or along with two other tests that are used to distinguish between different autoimmune disorders. These include:
- MPO antibodies
- PR3 antibodies
Additional tests that may be performed to aid in a diagnosis include ESR (erythrocyte sedimentation rate) to check for inflammation, FBC (full blood count) to measure and evaluate white and red blood cells, complement levels to assess inflammation and creatinine to evaluate kidney function. Sometimes an ANCA test may be requested to monitor the response to therapy, follow the course of the disease, and/or to detect a relapse.
When is it requested?
An ANCA test and/or tests for MPO and PR3 are requested when a person is suspected of having a systemic autoimmune vasculitis, especially when symptoms suggest Granulomatosis with polyangitis (GPA ) or microscopic polyangiitis. Early in the disease, symptoms may be vague or nonspecific, such as fever, fatigue, weight loss, muscle and/or joint aches, and night sweats.
- Eyes — red, itchy eyes or "pink eye" (conjunctivitis); problems with sight (blurry vision, loss of vision)
- Ears — hearing loss
- Nose — runny nose or other upper respiratory symptoms that do not go away
- Skin — rashes and/or granulomas
- Lungs — cough and/or difficulty breathing
- Kidneys — abnormal amounts of protein in the urine
Some laboratories will perform all three tests, ANCA, MPO and PR3, as a panel while others will perform MPO and PR3 only if an initial ANCA test is positive.
Testing may also be performed periodically to monitor a person who has been diagnosed with an autoimmune vasculitis.
What does the test result mean?
Results of ANCA tests must be interpreted carefully and take several factors into account. A doctor will consider clinical signs and symptoms and results of other types of tests such as imaging studies when determining a diagnosis.
Positive ANCA, PR3, and/or MPO tests help to support a diagnosis of systemic autoimmune vasculitis and to distinguish between different types. However, to confirm a diagnosis, a biopsy of an affected site is most often required. Negative tests results make it less likely that a person's symptoms are due to an autoimmune vasculitis.
Most often, ANCA tests are performed using indirect immunofluorescence microscopy after a sample has been tested and is positive for MPO or PR3. Serum samples are mixed with neutrophils to allow autoantibodies that may be present to react with the cells. The sample is put on a slide and treated with a fluorescent stain. The slide is then examined under a microscope and the resulting pattern noted.
Several different ANCA patterns may be seen:
- Perinuclear (p-ANCA) – most of the fluorescence occurs near the nucleus. About 90% of samples with a p-ANCA pattern will have MPO antibodies.
- Cytoplasmic (c-ANCA) – the fluorescence occurs throughout the cytoplasm of the cell. About 85% of samples with a c-ANCA pattern will have PR3 antibodies.
- Negative ANCA — very little or no fluorescence
- Atypical p-ANCA — seen in many cases of ulcerative colitis as well as some patients with Crohn's disease and rheumatoid arthritis.
The majority of laboratories will follow the new international guidance and the ANCA IIF will only be performed on samples already screened and known to be positive for MPO or PR3;
- A positive test for PR3 antibodies and a positive c-ANCA or p-ANCA are seen in more than 80% of patients with active GPA
- A positive test for MPO antibodies and a positive p-ANCA are consistent with microscopic polyangitis, glomerulonephritis, Churg-Strauss syndrome, and Goodpasture's syndrome. MPO and p-ANCA may also be present non specifically in other autoimmune disorders, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.
The following table shows results that may be seen in some vasculitis conditions.
Condition % of patients with c-ANCA pattern (PR3 antibodies) % of patients with p-ANCA pattern (MPO antibodies) Granulomatosis with polyangitis (GPA) 90% in active disease, 60-70% no active disease Less than 10% Microscopic polyangiitis 30% 60% Churg-Strauss syndrome Rare 50-80% Polyarteritis nodosa Rare Rare
ANCA levels can change over time and may sometimes be used in a general way to monitor disease activity and/or response to therapy.
Is there anything else I should know?
Will my ANCA, PR3 and MPO autoantibodies ever go away?
Can the ANCA test be performed in my doctor's surgery?
Should everyone have an ANCA test done?
Are there conditions other than vasculitis that can cause a positive ANCA?
How many autoimmune disorders cause systemic vasculitis?
There is quite a long list of autoimmune disorders that have been identified (see the Links tab for more on these). They are organised, with some overlap, by the size of the blood vessels that they affect – small, medium, or large.