An Anti-Neutrophil Cytoplasmic Antibody (ANCA) test is a blood test that identifies specific autoantibodies, which are proteins the immune system produces. Sometimes, the immune system mistakenly produces autoantibodies that target the body’s own healthy cells and tissues, leading to autoimmune diseases.
ANCAs specifically target neutrophils, a type of white blood cell that is a component of the body’s inflammatory response. This attack on neutrophils can cause them to damage blood vessels, resulting in inflammation and swelling. The presence of these autoantibodies is a signal that an autoimmune condition may be underway.
Purpose of ANCA Testing
Physicians order ANCA tests primarily to investigate a group of autoimmune disorders known as ANCA-associated vasculitis. These conditions can affect numerous organs, particularly the kidneys and lungs, and symptoms can be widespread. There are three main types of ANCA-associated vasculitis.
Granulomatosis with polyangiitis (GPA) affects the sinuses, lungs, and kidneys. Microscopic polyangiitis (MPA) involves the kidneys, lungs, nerves, and skin. Eosinophilic granulomatosis with polyangiitis (EGPA) is distinguished by asthma and a high number of eosinophils, and affects the lungs, nerves, and skin. The test also serves a function in gastroenterology, as it can help differentiate between the two main types of inflammatory bowel disease (IBD): ulcerative colitis and Crohn’s disease.
The Testing Procedure
The analysis happens within the laboratory using two primary methods. The initial screening is performed using a technique called Indirect Immunofluorescence (IFA). In this method, a patient’s blood serum is applied to a microscope slide containing prepared neutrophils. If ANCAs are present in the serum, they will bind to the neutrophils on the slide. A fluorescent antibody is then added, which attaches to the patient’s ANCAs.
When viewed under a special microscope, this process reveals specific staining patterns. The two most significant patterns are a cytoplasmic pattern (c-ANCA), where fluorescence appears throughout the cell’s cytoplasm, and a perinuclear pattern (p-ANCA), where fluorescence is concentrated around the nucleus.
A positive or ambiguous IFA result is followed by a second type of test known as an Enzyme-Linked Immunosorbent Assay (ELISA). The ELISA test identifies the precise protein within the neutrophils that the autoantibodies are targeting, adding a higher level of specificity. The two main targets identified by ELISA are Proteinase 3 (PR3) and Myeloperoxidase (MPO).
Interpreting ANCA Test Results
The interpretation of ANCA test results combines findings from both the IFA and ELISA methods. A positive result indicates the detection of ANCAs, while a negative result makes an ANCA-associated vasculitis less likely, though it does not rule it out. The specific pattern and protein target provide detailed diagnostic clues.
The combination of a c-ANCA pattern with a positive result for PR3 antibodies is strongly associated with Granulomatosis with polyangiitis (GPA). This specific combination is a significant indicator for physicians considering a GPA diagnosis. Conversely, a p-ANCA pattern is linked to the presence of MPO antibodies, a combination seen in patients with Microscopic polyangiitis (MPA) or Eosinophilic granulomatosis with polyangiitis (EGPA).
For individuals showing symptoms of IBD, a positive p-ANCA result can suggest ulcerative colitis over Crohn’s disease, as up to 80% of people with ulcerative colitis may have a positive ANCA test.
Test results also include a titer, which quantifies the concentration of the autoantibodies. The titer is determined by retesting the blood serum at increasing dilutions until the antibodies are no longer detectable. A higher titer, such as 1:160 compared to 1:20, signifies a greater concentration of ANCAs in the blood.
Role in the Diagnostic Process
An ANCA test is not a standalone diagnostic tool, as a definitive diagnosis relies on a combination of evidence. The results must be interpreted within the context of a patient’s complete clinical picture. Physicians synthesize the ANCA test results with a physical examination, patient symptoms, and findings from other diagnostic procedures. For vasculitis, this includes imaging studies like X-rays or CT scans to look for organ involvement and, frequently, a tissue biopsy to confirm the diagnosis.
Beyond the initial diagnosis, ANCA testing can play a role in managing the condition. Healthcare providers may monitor ANCA levels over time to assess treatment response or to detect a potential relapse. However, the utility of using the test for monitoring can vary, as changes in ANCA levels do not always correlate with disease activity.