JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
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Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing.

OBJECTIVE: Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution.

METHODS: We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period.

RESULTS: Of the 2345 samples tested over 2 years, 1998 were IF-negative. Among these IF-negative samples, 49 samples (2.5%) derived from 38 patients tested positive for MPO-ANCA or PR3-ANCA. Only 1 IF-negative, MPO/PR3-positive patient was subsequently diagnosed with ANCA-associated vasculitis (AAV). Eleven IF-negative, MPO/PR3-positive patients (29%) had been previously diagnosed and treated for AAV, all with positive IF and antibody tests prior to treatment. Four patients had evidence of cutaneous vasculitis not attributed to AAV, while several of the remaining IF-negative, MPO/PR3-positive patients had other immunologic disorders, including systemic lupus erythematosus (5 patients) and inflammatory bowel disease (3 patients).

CONCLUSION: In this real-life cohort assayed simultaneously by IF and multiplexed bead assays, the detection of MPO-ANCA or PR3-ANCA without a positive IF rarely led to a new diagnosis of systemic vasculitis, and was more likely to occur in the context of a non-vasculitic inflammatory condition. Our results suggest that concurrent IF and MPO/PR3 testing may be of limited use in preventing a missed diagnosis of new-onset AAV.

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