ANTI-PROTEINASE 3 AUTOANTIBODIES (ANTI-PR3)

CLINICAL UTILITY:

The systemic vasculitides are inflammatory diseases of the blood vessels and comprise a heterogeneous group of disorders, the causes of which are generally unknown. The diseases have diverse presentations, and are often rapidly progressive, causing irreversible injury to the vessels of kidneys and lungs. The presence of antineutrophil cytoplasmic antibodies (ANCA) in patients was first observed by Davies in 1982. ANCA are autoantibodies with specificities for proteins located in the primary and secondary granules of neutrophils and in the peroxidase-positive lysosomes of peripheral blood monocytes.

In the past few years, detection of ANCA autoantibodies has become a diagnostic tool for patients with vasculitis and glomerulonephritis. Using the indirect immunofluorescence technique with ethanol-fixed human neutrophils, different staining patterns were observed. Autoantibodies causing a C-ANCA (cytoplasmic pattern) antibodies are generally directed against proteinase 3 (PR-3) and can be specifically detected with the anti-PR-3 EIA. In contrast, P-ANCA antibodies can be produced by a variety of different autoantibody specificities. Originally, it was suspected that myeloperoxidase (MPO) was the target antigen of P-ANCA (perinuclear pattern), but later it became evident that only about half of P-ANCA findings are due to anti-MPO antibodies. A P-ANCA staining pattern can also be produced by other antibodies including elastase, lactoferrin, cathepsin G.

Today anti-PR-3 antibodies are of similar diagnostic value for Wegener's granulomatosis as anti-dsDNA antibodies for systemic lupus erythematosus. In a study consisting of 277 patients with WG and 1657 control patients, the specificity of anti-PR-3 antibodies for WG was determined to be 98%. The sensitivity of anti-PR-3 antibodies depended on disease activity and extent. It was found to be 93% for patients with active generalized disease, 60% for patients with active regional disease and 40% for patients in remission. In follow-up studies it was demonstrated that autoantibody changes paralleled changes in disease activity and helped to distinguish relapses of WG from other intercurrent illnesses, mainly infections, which are always a threat for patients on immunosuppressive treatment. In a 15 month prospective study on 35 patients with WG, seventeen relapses were observed which were all proceeded (by a mean period of 7 weeks) by a significant rise in C-ANCA-titer. Recently this group has shown that relapses in WG can be prevented by early treatment based on significant rises of C-ANCA-titers.

Anti-MPO and PR3 methods cannot replace the ANCA IFA method since there are too many other specificities that are important. This is especially true in the case of atypical ANCA patterns that have been associated with a variety of conditions including inflammatory bowel disease. The anti-MPO and PR3 EIA methods can provide an important confirmatory result for two of the more important antibodies and is useful as an aid in interpreting difficult IFA samples.

METHOD DESCRIPTION:

Anti-Proteinase 3 Autoantibodies are measured colorimetrically using a solid phase immunoenzymatic assay (“sandwich” technique).

REFERENCE RANGE:

Negative: <10 U/mL; Indeterminate: 10-20 U/mL; Low Positive: 21-30 U/mL; Positive:>31 U/mL

SPECIMEN REQUIREMENTS:

0.5 ml serum is required (0.3 ml minimum). Refrigerate or freeze.