Antineutrophil cytoplasmic antibodies (ANCA) are found in several vasculitic conditions, including granulomatosis with polyangiitis, microscopic polyangiitis, and Churg-Strauss syndrome. Cytoplasmic ANCA (c-ANCA) represents a subset of these antibodies, in which the primary molecular target is proteinase-3 within the cytoplasm of neutrophils and monocytes. The role of c-ANCA in Wegener granulomatosis (WG) is unclear and unlikely to be pathogenic, as high titers do not correlate well with disease severity and may remain positive even with treatment and remission. 
An absence of c-ANCA or titers less than 1:20 are generally considered a negative result. However, different laboratories may have different upper limits of normal, and any individual result should be interpreted through the reference range of the performing lab.
c-ANCA testing is performed in the initial evaluation and follow-up of patients with granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis.  This testing is performed in a 2-step approach. First, indirect fluorescent antibody detects the presence of antinuclear cytoplasmic antibodies; this positive result is followed by ELISA testing for presence and titer of antibodies specifically against proteinase-3. 
In diagnosing GPA, the c-ANCA results should be interpreted while considering the patient’s presentation. In those with currently active systemic disease, elevated c-ANCA titers are over 98% sensitive and specific for GPA. In patients with limited disease, with an atypical presentation, or without the full spectrum of GPA manifestations, the sensitivity drops to 60-70%. [4, 5, 6] For further details about classifying disease severity and presentation, see the topic Wegener Granulomatosis.
In patients with positive c-ANCA, the level of titer elevation is a poor indicator of disease activity. Patients currently in remission may have persistent, several-fold elevations in c-ANCA titer; most of these patients do not develop a relapse in the future. Conversely, patients with rapidly declining titers may have persistent residual disease. The elevation in titer can, however, be used for increased vigilance during patient follow-up, with the intent of maintaining a higher index of suspicion for a relapse in patients with persistently raised levels. c-ANCA titers serve no role in dictating treatment and cannot be used to guide immunomodulatory therapy or deliver prognostic information to the patient. [1, 7]
The use of serial c-ANCA titers in following patients with established vasculitis for evidence of relapse has been a controversial issue. Although some studies have shown value in following titers, the high incidence of false-positive and false-negative results precludes a general recommendation. As such, the patient’s current symptoms and other lab studies are a better indicator of relapsing disease. [1, 8]
Collection and Panels
c-ANCA is performed on serum drawn during a random spot test.
Invalidation: Lipemia, gross hemolysis, bacterial contamination
Storage conditions: Refrigerated
Panels: c-ANCA is usually performed as a reflex test after a positive ANCA indirect immunofluorescence panel.
Granulomatosis with polyangiitis is a rare, necrotizing form of small-vessel vasculitis that classically manifests as a pulmonary-renal syndrome; patients develop hemoptysis and dyspnea, sinusitis and epistaxis, and frequently a rapidly progressive glomerulonephritis. Patients may also have ocular, cutaneous, neuropathic, and rheumatologic findings. [1, 9, 10, 11, 12]
Antineutrophil cytoplasmic antibodies (ANCA) are found in several vasculitic conditions, including granulomatosis with polyangiitis, microscopic polyangiitis, and Churg-Strauss syndrome. c-ANCA represents a subset of these antibodies, in which the primary molecular target is proteinase-3 within the cytoplasm of neutrophils and monocytes. The role of c-ANCA in WG is unclear and unlikely to be pathogenic, as high titers do not correlate well with disease severity and may remain positive even with treatment and remission. 
c-ANCA is drawn during the evaluation of a patient with signs and symptoms suspicious for WG. After a c-ANCA returns back positive, frequently a tissue biopsy is needed to firmly establish the diagnosis.
c-ANCA has a specificity approaching 100%, especially in patients with active disease. However, several conditions may very rarely result in a false positive result. These include tuberculosis, Hodgkin disease, HIV infection, and multiple myeloma.