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  • Title: Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis and other diseases: clinical issues.
    Author: Galperin C, Hoffman GS.
    Journal: Cleve Clin J Med; 1994; 61(6):416-27. PubMed ID: 7828332.
    Abstract:
    BACKGROUND: An association between antineutrophil cytoplasmic antibodies (ANCA) and nonimmune complex-mediated glomerulonephritis was first reported over 10 years ago. In Wegener's granulomatosis, the antibody usually binds proteinase 3. Antibodies to a variety of other antigens have been identified in a broad range of diseases. SUMMARY: The typical coarse, granular cytoplasmic ANCA pattern on indirect immunofluorescence almost always indicates reactivity with proteinase 3, whereas the perinuclear ANCA pattern may reflect reactivity with a host of different antigens. Antibodies to proteinase 3 are overwhelmingly associated with Wegener's granulomatosis (specificity > or = 90%). In a significant number of patients, however, disease activity is not linked to an ANCA titer. ANCA may play a role in the pathogenesis of many types of inflammatory conditions. Antibodies to proteinase 3 may be important in predisposing to Wegener's granulomatosis, but definitive in vivo proof of their role is not yet available. KEY POINTS: The presence of cytoplasmic ANCA in a patient who is suspected to have Wegener's granulomatosis is strong circumstantial evidence in support of that diagnosis. However, it does not represent absolute proof and should be viewed with skepticism if the clinical presentation is atypical. Conversely, a negative ANCA in the setting of a typical presentation should not rule out Wegener's granulomatosis. Because ANCA titers may not always vary in tandem with disease activity, the decision to modify therapy for Wegener's granulomatosis should continue to be based on clinical judgment.
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