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Diagnostic value of classical and atypical antineutrophil cytoplasmic antibody (ANCA) immunofluorescence patterns
R C Wong1, R A Silvestrini, J A Savige
1Immunopathology Department, ICPMR, Westmead Hospital, NSW, Australia. rcwwong@hotmail.com
Insights
Classifying cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA) patterns improves diagnostic accuracy. Strict adherence to the "classical" C-ANCA pattern enhances correlation with antiproteinase-3 antibodies (PR3-ANCA) and systemic vasculitis diagnosis.
Area of Science:
- Immunology
- Clinical Chemistry
- Rheumatology
Background:
- The classical C-ANCA pattern on indirect immunofluorescence (IIF) is granular with central accentuation, strongly linked to PR3-ANCA and Wegener's granulomatosis.
- Broad reporting of any cytoplasmic IIF staining as C-ANCA can diminish its diagnostic specificity and value.
- Distinguishing specific C-ANCA patterns is crucial for accurate clinical interpretation.
Purpose of the Study:
- To classify distinct cytoplasmic ANCA (C-ANCA) immunofluorescence patterns.
- To evaluate if applying stringent classical C-ANCA criteria improves correlation with PR3-ANCA enzyme-linked immunosorbent assay (ELISA) results.
- To assess the association between classical C-ANCA patterns and a diagnosis of systemic vasculitis, including Wegener's granulomatosis.
Main Methods:
- Analysis of 72 sera exhibiting cytoplasmic IIF patterns over two years.
- Standard indirect immunofluorescence (IIF) for C-ANCA pattern classification.
- Detection of antiproteinase-3 antibodies (PR3-ANCA) using a commercial ELISA kit.
Main Results:
- Three patterns identified: 'classical/true' C-ANCA (37.5%), 'flat' ANCA (29%), and 'atypical' ANCA (33.5%).
- Classical C-ANCA sera showed a 92.5% correlation with PR3-ANCA positivity (p < 0.0001), unlike flat or atypical patterns.
- 87% of patients with classical C-ANCA had Wegener's granulomatosis or systemic vasculitis, compared to none with flat ANCA.
Conclusions:
- Restricting the definition of C-ANCA to the classical pattern with central/interlobular accentuation significantly improves diagnostic utility.
- This stringent classification enhances the correlation between C-ANCA IIF results, PR3-ANCA ELISA positivity, and systemic vasculitis diagnosis.
- Refined C-ANCA pattern recognition is essential for accurate diagnosis of autoimmune conditions like Wegener's granulomatosis.
Background:
The "classical" antineutrophil cytoplasmic antibody (C-ANCA) pattern seen on indirect immunofluorescence (IIF) is characterised by granular cytoplasmic staining showing central or interlobular accentuation, and is strongly associated with antiproteinase-3 antibodies (PR3-ANCA) and Wegener's granulomatosis. However, many laboratories report C-ANCA in the presence of any cytoplasmic IIF staining, regardless of pattern, which risks reducing the diagnostic value of this pattern.
Aims:
To classify different cytoplasmic ANCA patterns and thus determine whether stringent application of the classical criteria for C-ANCA would produce better correlation between C-ANCA and (1) PR3-ANCA enzyme linked immunosorbent assay (ELISA) results; (2) a diagnosis of systemic vasculitis (including Wegener's granulomatosis).
Methods:
72 sera with cytoplasmic IIF collected over a two year period were analysed by IIF and a commercial PR3-ANCA ELISA kit.
Results:
Three IIF patterns were defined: "classical/true" C-ANCA as described above (n = 27 (37.5%)); "flat" ANCA with homogeneous cytoplasmic staining (n = 21 (29%)); and "atypical" ANCA which included all other cytoplasmic patterns (n = 24 (33.5%)). Twenty five of the 27 true C-ANCA sera (92.5%) contained PR3-ANCA (p < 0.0001), but none of the 21 with flat ANCA and only one of the 24 with atypical ANCA. From clinical data on 23 of the 27 true C-ANCA positive patients, 20 (87%) had evidence of Wegener's granulomatosis or systemic vasculitis (p < 0.0001 v the other two patterns). However, none of 19 sera with flat ANCA and clinical data had evidence of systemic vasculitis.
Conclusions:
Restricting the term "c-ANCA" to the "classical" description of central/interlobular accentuation on IIF, will improve its correlation with PR3-ANCA positivity and a diagnosis of systemic vasculitis.
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