The clinical utility of ANCA positivity.

It is six years since a leader in the Annals reviewed the performance of antineutrophil cytoplasmic antibodies (ANCA) in clinical practice.' At that time there was increasing confidence in the value of ANCA testing in the diagnosis ofWegener's granulomatosis and related primary vasculitides. Sensitivity of cANCA for Wegener's granulo-matosis was reported as 500/o-96% and specificity was 900/o-100%. What is our current understanding of the place of ANCA testing in the diagnostic process? Methodology Clinicians need to be aware of the different methods used to detect ANCA, their relative merits, and their potential pitfalls. Indirect immunofluorescent examination of a patient's serum on ethanol fixed neutrophils remains the method of choice.2 Two major staining patterns, classic cANCA and perinuclear pANCA, can be identified; however, the recognition of the distinct patterns is not always easy and particular care is needed to ensure that ANCA are not confused with other autoantibodies and vice versa.3 The main target antigens of ANCA are proteinase 3 (cANCA) and myeloperoxidase (pANCA) but antibodies to several other antigens will produce the patterns of pANCA (lactoferrin, cathepsin G, and elastase) and cANCA (cationic protein 57). Despite this, the correlation of indirect immunofluorescence pattern with antigen is not absolute, and the clinical importance of the different antigenic specificities of ANCA is not entirely established.4 5Antigen specific, solid phase assays have been developed to provide quantitative results, but multiple assays would be required to completely replace indirect immunofluorescence and these are not yet standardised.6 A reliable ANCA service continues, therefore, to be dependent on the accurate interpretation of findings from indirect immunofluorescence. Disease associations Davies et al first described ANCA in a series of eight patients with necrotising glomerulonephritis in whom there was serological evidence of recent arbovirus infection.7 In 1985, van der Woude et al proposed that ANCA were useful both in the diagnosis and monitoring of disease activity in Wegener's granulomatosis.8 As the indirect immunofluorescence patterns were defined, it seemed that cANCA was associated almost exclusively with Wegener's granulomatosis and pANCA with renal limited forms of microscopic polyangiitis.9 A further, intermediate staining pattern termed atypical or xANCA was described in ulcerative colitis.'0 Isotype specificity was also reported. IgA ANCA were described in Henoch-Schonlein purpura and IgM ANCA were reported in association with severe pulmonary haemorrhage. " I A distinct indirect immunofluorescence pattern was described in Kawasaki disease, although this has recently been retracted by that group.'2 It also became clear …