The importance of distinguishing and reporting different perinuclear ANCA (P-ANCA) immunofluorescence patterns: a prospective study

Abstract

The 1999 International ANCA consensus statement does not require laboratories to distinguish between different perinuclear ANCA (P-ANCA) IIF patterns, including those produced by positive anti-nuclear antibodies (ANA). However, they recommend correlation with results of MPO/PR3-ANCA ELISA testing. Aims To investigate the clinical associations of the ‘classical/ textbook’ P-ANCA, atypical P-ANCA (AP) and ANA/uninterpre-table patterns, with or without MPO/PR3-ANCA ELISA results, to determine whether different P-ANCA patterns should be distinguished and reported. Methods All routine ANCA requests (n = 3544) from January to April 2010 were studied prospectively regarding P-ANCA IIF patterns, MPO/PR3-ANCA ELISA results, and clinical/other laboratory evidence of vasculitis. Results Four hundred and thirty-six (436) samples demonstrated positive perinuclear ANCA immunofluorescence, including the classical P-ANCA pattern (n = 45), atypical P-ANCA pattern (n = 163) and ANA/uninterpretable patterns (n = 228). The ‘classical/textbook’ P-ANCA pattern had a significantly stronger association with vasculitis (31/45) compared to the atypical P-ANCA pattern (2/163), positive ANA/uninterpretable patterns (11/228), or all P-ANCA patterns combined (44/436) (all p values <0.0001). The combination of a positive ELISA result with a classical P-ANCA pattern was more likely to be associated with vasculitis than a positive ELISA result irrespective of corresponding IIF pattern (25/29 versus 33/62; p < 0.001). Conclusion This study demonstrates the importance of distinguishing the ‘classical/textbook’ P-ANCA pattern from both atypical P-ANCA and ANA/uninterpretable patterns, especially as the latter two patterns occur more frequently. Combining MPO/ PR3-ELISA and IIF results improves the association with vasculitis compared with either ELISA or IIF results alone. The 1999 International ANCA consensus statement does not require laboratories to distinguish between different perinuclear ANCA (P-ANCA) IIF patterns, including those produced by positive anti-nuclear antibodies (ANA). However, they recommend correlation with results of MPO/PR3-ANCA ELISA testing. To investigate the clinical associations of the ‘classical/ textbook’ P-ANCA, atypical P-ANCA (AP) and ANA/uninterpre-table patterns, with or without MPO/PR3-ANCA ELISA results, to determine whether different P-ANCA patterns should be distinguished and reported. All routine ANCA requests (n = 3544) from January to April 2010 were studied prospectively regarding P-ANCA IIF patterns, MPO/PR3-ANCA ELISA results, and clinical/other laboratory evidence of vasculitis. Four hundred and thirty-six (436) samples demonstrated positive perinuclear ANCA immunofluorescence, including the classical P-ANCA pattern (n = 45), atypical P-ANCA pattern (n = 163) and ANA/uninterpretable patterns (n = 228). The ‘classical/textbook’ P-ANCA pattern had a significantly stronger association with vasculitis (31/45) compared to the atypical P-ANCA pattern (2/163), positive ANA/uninterpretable patterns (11/228), or all P-ANCA patterns combined (44/436) (all p values <0.0001). The combination of a positive ELISA result with a classical P-ANCA pattern was more likely to be associated with vasculitis than a positive ELISA result irrespective of corresponding IIF pattern (25/29 versus 33/62; p < 0.001). This study demonstrates the importance of distinguishing the ‘classical/textbook’ P-ANCA pattern from both atypical P-ANCA and ANA/uninterpretable patterns, especially as the latter two patterns occur more frequently. Combining MPO/ PR3-ELISA and IIF results improves the association with vasculitis compared with either ELISA or IIF results alone.