- Last Update On : 2013-02-17
Systemic necrotizing vasculitides are inflammatory diseases of blood vessels, which are difficult to distinguish from infectious, connective tissue, and degenerative diseases. Biopsies often reveal only nonspecific acute or chronic inflammation. Standard laboratory tests such as hemoglobin, WBC, ESR, ANA, and urinalysis have poor predictive value for vasculitis, because none of them are specific for vasculitis. Abnormalities merely reflect inflammation and organ damage. Negative results are often helpful in ruling out vasculitis.
Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in the primary systemic small vessel vasculitides such as Wegener granulomatosis (WG), microscopic polyangiitis (MPA) and pauci-immune necrotizing glomerulonephritis (PING). Traditionally, ANCA antibodies have been detected by indirect immunofluorescence (IF) microscopy. Two different IF staining patterns have been identified, cytoplasmic (C-ANCA) and perinuclear (P-ANCA), which reflect different antigenic specificities. The major target antigens for ANCA have been found to be enzymes present in neutrophil granules. The C-ANCA pattern is strongly associated with antibodies against proteinase 3 (PR3). The P-ANCA pattern has been associated with several enzymes, among which myleoperoxidase (MPO) is the most frequent.
Disadvantages of the IF test include the lack of antigen specificity, occurrence of atypical fluorescent patterns, subjective interpretation and tedious methodology. Recently, more specific and reliable enzyme immunoassays for PR3 ANCA and MPO ANCA have become available.
Preliminary results have demonstrated the following performance characteristics.
- Approximately 60% of patients with MPA or PING have MPO ANCA and 30% have PR3 ANCA.
- Approximately 80% of patients with active WG have PR3 ANCA and up to 20% have MPO ANCA
- ANCA cannot be relied upon exclusively to establish the diagnosis of autoimmune vasculitis (WG, MPA, or PING) because some of these patients have antibodies to other neutrophil antigens, e.g., cathepsin or elastase.
- While the presence of PR3 ANCA is highly specific for WG, it is recommended that positive test results be confirmed by another testing method. SLRL will automatically test all samples that are positive for MPO or PR3 ANCA by IF microscopy. Simultaneous presence of PR3 ANCA and C-ANCA has a specificity of 98% for WG.
- Patients with rheumatoid arthritis and HIV are most likely to have falsely positive MPO and PR3 ANCA
- At this time, the results of PR3 ANCA have not been proven useful for monitoring disease activity. Sequential measurements of C-ANCA by IF should be followed to monitor disease activity and response to treatment.
Test performance can be enhanced by only ordering ANCA tests for patients with at least one of the following clinical indications.
- Glomerulonephritis, especially rapidly progressive
- Pulmonary hemorrhage, especially pulmonary renal syndrome
- Cutaneous vasculitis with systemic features
- Multiple lung nodules
- Chronic obstructive disease of the upper airways
- Long standing sinusitis or otitis
- Subglottic tracheal stenosis
- Mononeuritis multiplex or other peripheral neuropathy
- Retro-orbital mass
The reference range for both assays changed to 0-20 units.
Specimen requirement is one red top or SST tube of blood.