ANTI-MYELOPEROXIDASE AUTOANTIBODIES (ANTI-MPO)

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.

Anti-MPO antibodies proved highly sensitive and specific for idiopathic and vasculitis-associated crescentic glomerulonephritis, and also for classic polyarteritis nodosa, Churg-Strauss syndrome, and the polyangiitis overlap syndrome without renal involvement. With respect to sensitivity, either anti-MPO or anti-PR-3 antibodies were found in 77% to 100% of patients with idiopathic and vasculitis-associated crescentic glomerulonephritis. In Wegener's granulomatosis, anti-MPO is detected only occasionally and generally in patients negative for anti-PR-3 antibodies. Coexisting antibodies to PR3 and MPO is very unusual. Preliminary data indicate that levels of anti-MPO antibodies are significantly higher during active phases of diseases compared to phases of remission. Thus, these autoantibodies, like anti-PR-3 antibodies, seem to be marker of disease activity. Longitudinal testing performed in one patient revealed an increase in anti-MPO antibodies even prior to a relapse. Since the indirect immunofluorescence technique is not specific for detection of anti-MPO antibodies, future studies using appropriate assays will provide more extensive data on the sensitivity and specificity of these autoantibodies.

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-Myeloperoxidase Autoantibodies are measured colorimetrically using a solid phase immunoenzymatic assay ("sandwich" technique).

REFERENCE RANGE:

<10 U Negative; 10-20 U Indet; 21-30 U Low Positive; >30 U Positive

SPECIMEN REQUIREMENTS:

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