Test ID: PR3    
Proteinase 3 Antibodies, IgG, Serum

Evaluating patients suspected of having Wegener granulomatosis (WG)

Distinguishing between WG and other forms of vasculitis, in conjunction with:

-MPO / Myeloperoxidase Antibodies, IgG, Serum

-ANCA / Cytoplasmic Neutrophil Antibodies, Serum (may be obtained as VASC / Antineutrophil Cytoplasmic Antibodies Vasculitis Panel, Serum)

May be useful to follow treatment response or to monitor disease activity in patients with myeloperoxidase antibodies

Proteinase 3 (PR3) antigen is a 29-kD serine protease that exists as a protein triplet in human neutrophils.

Wegener granulomatosis (WG) is an autoimmune vasculitis that affects the kidneys and lungs, as well as other organs. Patients with WG develop autoantibodies to the PR3 antigen of myeloid lysosomes (PR3 antineutrophil cytoplasmic antibodies [PR3 ANCA]).(1)

Since it is often impossible to distinguish between WG and other forms of vasculitis on the basis of clinical signs and symptoms, tests for PR3 ANCA should be employed with other serologic tests in the initial diagnostic evaluation of patients with clinical features of vasculitis (eg, VASC / Antineutrophil Cytoplasmic Antibodies Vasculitis Panel, Serum).

<0.4 U (negative)

0.4-0.9 U (equivocal)

> or =1.0 U (positive)

Reference values apply to all ages.

Proteinase 3 antineutrophil cytoplasmic antibodies (PR3 ANCA) are detectable in nearly all patients with severe active Wegener granulomatosis (WG).(2) The presence of PR3 ANCA is a specific diagnostic indicator of WG; less than 2% of positive results occur in patients who do not have the disease.(3,4)

A negative result for PR3 ANCA diminishes the likelihood that a patient has active WG; but, approximately 20% of patients with limited WG may test negative for PR3 ANCA.(3)

The levels of PR3 ANCA often decline following successful treatment of patients with WG. Nevertheless, follow-up testing for PR3 ANCA to evaluate clinical status in treated patients should be used with caution as the levels of antibodies may correlate poorly with clinical status in some patients.

While the presence of proteinase 3 antineutrophil cytoplasmic antibodies (PR3 ANCA) is highly specific for Wegener granulomatosis (WG), it is recommended that positive test results obtained by immunoassay be confirmed by another testing method.(4) This is best accomplished by testing for cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA) by indirect immunofluorescence microscopy (ANCA / Cytoplasmic Neutrophil Antibodies, Serum). Alternately, VASC / Antineutrophil Cytoplasmic Antibodies Vasculitis Panel, Serum includes tests for PR3 ANCA, myeloperoxidase antibodies, and, if indicated, cANCA and pANCA. This panel is recommended for the initial diagnostic evaluation of patients clinically suspected of having systemic vasculitis. The simultaneous presence of PR3 ANCA and cANCA has a specificity greater than 99% for WG.(3)

1. van der Woude FJ, Rasmussen N, Lobatto S, et al: Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener granulomatosis. Lancet 1985;1:425-429

2. Finkleman JD, Lee AS, Hummel AM, et al: ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis. Am J Med 2007;120:643

3. Russel KA, Wiegert E, Schroeder DR, et al: Detection of anti-neutrophil cytoplasmic antibodies under actual clinical testing conditions. Clin Immunol 2002;103:196-203

4. Savige J, Gillis D, Benson E, et al: International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 1999;111:507-513