The utility of detecting of autoantibodies against neutrophil cytoplasmic components in Wegener's granulomatosis.

Establishing the diagnosis of Wegener's granulomatosis (WG) can be very difficult, especially early in the disease or in limited forms of this illness where renal and/or pulmonary involvement does not occur. Recent reports have suggested that tests to measure levels of antineutrophil cytoplasmic antibodies (ANCA) are useful in the diagnosis and management of WG. We developed an enzyme-linked immunoassay (ELISA) utilizing neutrophil granules and their fractions to detect such antibodies. We identified the major antigen in patients with WG as contained in a protein peak of 25-30,000 molecular weight. ELISA testing of patient, normal control, and disease control sera showed that the ELISA test suffered from a lack of specificity. It detected positive results in 19 of 49 disease control sera that were primarily from patients with diseases such as lupus erythematosus. Visual examination, by indirect immunofluorescence using patients' sera to stain normal fixed neutrophils, identified the coursely speckled (granule associated) WG binding pattern in seven of eight WG patients and this was distinguishable from the pattern of binding in non-WG sera. While the techniques such as the ELISA and flow cytometry are useful in identifying sera with antineutrophil cytoplasmic antibodies, positive sera should still be examined by visual fluorescence microscopy when entertaining the diagnosis of WG. Under these circumstances, tests for ANCA will be very useful in the diagnosis and management of WG.