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At a Glance

Why Get Tested?

To help detect, diagnose, and sometimes monitor certain forms of systemic vasculitis (an autoimmune disorder that causes inflammation of blood vessels)

To help distinguish between Crohn disease (CD) and ulcerative colitis (UC), the two most common types of inflammatory bowel disease (IBD); as an adjunct to other IBD testing

When To Get Tested?

When you have symptoms such as fever, muscle aches, and weight loss or impaired kidney or lung function that your healthcare practitioner thinks may be due to a vascular autoimmune disorder

When you have symptoms such as persistent or intermittent diarrhea and abdominal pain that your health practitioner suspects may be due to an IBD; when your health practitioner wants to distinguish between CD and UC

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

What is being tested?

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies produced by the immune system that mistakenly target and attack specific proteins within neutrophils (a type of white blood cell). ANCA testing detects and measures the amount of these autoantibodies in the blood. Two of the most common ANCAs are the autoantibodies that target the proteins myeloperoxidase (MPO) and proteinase 3 (PR3). These are called pANCAs and cANCAs, respectively.

There are two types of ANCA tests:

The first type is called Indirect Immunofluorescence (IIF). This uses neutrophils fixed onto a slide. For the test, serum from your blood sample is mixed with the neutrophils on the slide and any ANCAs in the sample attach to the neutrophil proteins. Treatment of the slide with a fluorochrome-stained antibody reacts with any ANCA present. This produces a pattern of fluorescence that can be seen under a microscope. The pattern may be identified as cytoplasmic (cANCA), perinuclear (pANCA), or atypical ANCA (X-ANCA).

Alternatively, the laboratory may test for antibodies to myeloperoxidase or to proteinase 3 directly using an ELISA assay.

A combination of both fluorescence and ELISA tests are often done when testing suspected cases of vasculitis.

ANCA may be present in several autoimmune disorders that cause inflammation, tissue damage, and organ failure:

  • Systemic vasculitis is a group of disorders associated with damage and weakening of blood vessels. It can cause tissue and organ damage due to the narrowing and obstruction of 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 systemic vasculitis depend upon the degree of autoimmune activity and the parts of the body involved. A few types of systemic vasculitis are closely associated with the production of ANCA:
    • Granulomatosis with polyangiitis (Wegener granulomatosis)
    • Microscopic polyangiitis
    • Eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome)
    • Polyarteritis nodosa (PAN)

cANCA/PR3 antibodies are most frequently seen in granulomatosis with polyangiitis and pANCA/ MPO antibodies are most often associated with microscopic polyangiitis. However, both may be seen in all three types with varying degrees of reactivity.

  • Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) associated with swollen and damaged tissues in the lining of the colon. UC can be difficult to distinguish from Crohn disease (CD), another type of IBD that can affect any part of the intestinal tract. The presence of atypical ANCA is generally associated with UC (80% of patients), while only 20% of CD patients may be positive.

Common Questions

How is the test used?

Tests for antineutrophil cytoplasmic antibodies (ANCA) may be used to:

  • Help detect and diagnose certain forms of autoimmune vasculitis, including granulomatosis with polyangiitis (Wegener granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome). Sometimes this test may also be used to monitor treatment and/or detect a relapse of these conditions.
  • Help distinguish between ulcerative colitis (UC) and Crohn disease (CD), two common types of inflammatory bowel disease (IBD).

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.

When is it ordered?

Vasculitis
An ANCA test and/or tests for MPO and PR3 are ordered when you have signs and symptoms that suggest systemic autoimmune vasculitis. Early in the disease, symptoms may be vague or nonspecific, such as fever, fatigue, weight loss, muscle and/or joint aches, and night sweats. As the disease progresses, damage to blood vessels throughout the body may cause signs and symptoms associated with complications involving various tissues and organs. A few examples include:

  • 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 —protein in the urine

Testing may also be performed periodically when you are being treated for autoimmune vasculitis.

Inflammatory Bowel Disease
An ANCA test may be ordered with a test for anti-Saccharomyces cerevisiae antibodies (ASCA) when you have signs and symptoms that suggest inflammatory bowel disease and your health care practitioner is attempting to distinguish between Crohn disease and ulcerative colitis.

Symptoms of an IBD may include:

  • Abdominal pain and cramps
  • Diarrhea
  • Rectal bleeding
  • Fever
  • Fatigue
  • In some people, joint, skin, bone, and organ-related symptoms
  • Children may also have delayed development and growth retardation.

What does the test result mean?

Results of ANCA tests must be interpreted carefully, taking several factors into account. A healthcare practitioner will consider your signs and symptoms in addition to results of the laboratory tests and other types of tests, such as imaging studies.

Vasculitis

Positive test results for ANCA, PR3, and/or MPO help support a diagnosis of systemic autoimmune vasculitis and distinguish between different types of vasculitis. However, to confirm a diagnosis, a biopsy of an affected site is often required.

Negative ANCA tests results mean it is unlikely that your symptoms are due to an autoimmune vasculitis.

For a positive result on the indirect immunofluorescence microscopy method, different ANCA patterns may be seen:

  • Perinuclear (pANCA) – most of the fluorescence occurs near the nucleus; about 90% of samples with a pANCA pattern will have MPO antibodies.
  • Cytoplasmic (cANCA) – the fluorescence occurs throughout the cytoplasm of the cell; about 85% of samples with a cANCA pattern will have PR3 antibodies.
  • Atypical ANCA – a positive fluorescence staining is present but does not resemble a pANCA or a cANCA pattern.
  • Negative ANCA – very little or no fluorescence

If an ANCA test result is positive, then an additional step may be performed to determine the amount of antibody present. This is called a titer. To determine the titer, a serum sample is diluted in steps and each dilution is tested for the presence of the antibody. The greatest dilution at which the antibody can be detected is the titer. For example, if a serum tests positive after being diluted 64-fold, the titer is 1:64. The higher the titer, the more antibody is present in the blood.

ANCA levels can change over time and may sometimes be used in a general way to monitor disease activity and/or response to therapy. However, in many individuals, titer levels may not correlate with the extent of disease activity.

  • Positive test results for PR3 antibodies and for cANCA or pANCA are seen in more than 80% of patients with active granulomatosis with polyangiitis (Wegener granulomatosis).
  • Positive test results for MPO antibodies and for pANCA are consistent with microscopic polyangitis, glomerulonephritis, eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome), and Goodpasture syndrome. MPO and pANCA may also be present 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.

Inflammatory Bowel Disease

In cases of suspected inflammatory bowel disease (IBD):

  • If ANCA is positive and ASCA (anti-Saccharomyces cerevisiae antibodies) is negative, then it is likely that you have ulcerative colitis (UC).
  • If ANCA is negative and ASCA is positive, then it is likely that you have Crohn disease (CD).
  • A person who is negative for ANCA and/or ASCA may still have UC, CD, or another IBD.

Besides ANCA, what other lab tests may be done?

Additional tests that may be performed to aid in diagnosis include erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) to check for inflammation, complete blood count (CBC) to measure and evaluate white and red blood cells, and urinalysis, blood urea nitrogen (BUN), and creatinine to evaluate kidney function. For some patients, tests for viruses such as hepatitis or cytomegalovirus may be ordered.

Since the symptoms associated with vasculitis and inflammatory bowel disease may be seen with a number of conditions, other tests are frequently performed prior to or along with ANCA testing to rule out other causes for the symptoms.

Is there anything else I should know?

In most cases, a biopsy of an affected blood vessel is necessary to confirm a diagnosis of autoimmune vasculitis.

Will my antineutrophil cytoplasmic antibodies (ANCA) ever go away?

Levels may fluctuate, but once you develop an autoantibody, you will continue to have it.

Can the ANCA test be performed at my local lab?

ANCA testing requires specialized equipment and careful interpretation by trained professionals. Your sample will need to be sent to a clinical laboratory that performs these tests and may be sent to a reference laboratory. Depending on the lab, it may take a few days to a week for results to be available.

Are there conditions other than vasculitis and inflammatory bowel disease that can cause a positive ANCA?

Yes. These conditions include rheumatoid arthritis, systemic lupus erythematosus (SLE), lung conditions, autoimmune hepatitis, use of certain drugs, and infections involving the heart (endocarditis) or the respiratory system.

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