Specimen Information

Type

Gold, SST

Volume

1.0 ml

Transport Info

Refrigerated 48 Hours
If specimen will not be received within 48 hours of collection, freeze serum and transport frozen

Fasting Required?

False

Clinical Significance

Diagnosis and follow-up of Wegener’s Granulomatosis (WG)
Evaluation of patients suspected of having systemic vasculitis, especially patients with renal disease or unexplained multi-organ disease possibly due to vasculitis
Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies specific for neutrophil lysosomal enzymes, particularly for proteinase-3 (PR-3, a serine proteinase) and myeloperoxidase (MPO). Cross-reaction has also been seen with cationic protein 57 (CAP 57), cathepsin G, elastase, lactoferrin, and other lysosomal proteins.Three major fluorescence patterns, perinuclear (p-ANCA), cytoplasmic (c-ANCA) and atypical (a-ANCA), are distinguished on ethanol-fixated neutrophils and confirmed by formalin-fixed neutrophils and Hep-2 cells.
The c-ANCA (cytoplasmic) pattern:The classic ANCA pattern appears as a diffuse granular cytoplasmic fluorescence and is specific for antibodies vs. serine proteinase-3 (PR-3). This pattern, characteristic of Wegener’s granulomatosis and to a lesser extent microscopic polyarteritis, has been designated c-ANCA. Patients with active generalized Wegener’s granulomatosis (WG) have a frequency of positive c-ANCA results (sensitivity) that is approximately 85-90%. A negative test of c-ANCA does not completely rule out WG. Positive c-ANCA results and antibodies to PR-3 can also be seen in polyarteritis nodosa. In patients with documented WG, rising titers of c-ANCA suggest relapse and falling titers suggest response to therapy.
The p-ANCA (perinuclear) pattern: The second ANCA pattern has been described as appearing as a perinuclear neutrophilic stain and has been designated p-ANCA. This pattern is specific for other neutrophilic enzymes, including myeloperoxidase (MPO), elastase, and lactoferrin. The most common target antigen associated with p-ANCA is MPO. p-ANCA is seen in association with a more organ-limited vasculitis, in particular pauci-immune necrotizing glomerulonephritis. p-ANCA is typically not seen in systemic vasculitis. In patients with active renal disease, a positive p-ANCA result suggests the presence of antibodies to MPO and pauci-immune necrotizing glomerulonephritis. However, positive p-ANCA results are not specific for MPO antibodies. Positive ANCA results (p-ANCA and, rarely, c-ANCA) may occur in patients with diseases other than WG or vasculitis, including Goodpasture’s syndrome, lupus erythematosus, rheumatoid arthritis, and Sjogren’s Syndrome.
The a-ANCA (atypical) pattern: This third type of ANCA pattern occurs when the initially positive p-ANCA cannot be confirmed by use of formalin-fixed slides and the ANA test is negative. This pattern has been observed in patients with ulcerative colitis and ascending cholangitis.