ANCA Diagnostics in Clinical Practice: New Developments (original) (raw)
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Antineutrophil cytoplasmic antibodies (ANCA)
Autoimmunity, 2005
Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80 -90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10 -20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear.
Clinical and Experimental Immunology, 2007
In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg–Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (–) sera (P < 0·01). Patients with IF+ PR3-MPO- sera showed the most varied reactivity to the minor antigens. Among the IF+ groups, the IF+ PR3+/MPO- sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.
Rheumatology International, 1996
In this study of antineutrophil cytoplasmic antibody (ANCA)-associated diseases, we determined the prevalence of other autoantibodies and the antigen specificities of ANCA. ANA were common, occurring in 7 of 36 (19%) patients with Wegener's granulomatosis, in 16 of 34 (47%) patients with microscopic polyarteritis, in 6 of 11 (55%) patients with segmental necrotising glomerulonephritis and in 8 of 18 (44%) of those with ANCAassociated systemic vasculitis without renal involvement. ANA were associated more often with pANCA and microscopic polyarteritis than with cANCA (P<0.05). Patterns were speckled (n = 23), homogeneous (n = 10) or nucleolar (n = 4). Anticardiolipin antibodies were also common, occurring in 10 of 25 (40%) patients with Wegener's granulomatosis, in 8 of 14 (57%) patients with microscopic polyarteritis and in 6 of 18 (33%) of those with a systemic vasculitis. However, anticardiolipin antibodies did not correlate with the presence of ANCA in any of the disease groups. Anti-GBM antibodies were demonstrated in only 2 of 25 (8%) patients with Wegener's granulomatosis, in l patient with microscopic polyarteritis (1/14, 7%) and in 1 with segmental necrotising glomerulonephritis (1/11,9%). All four patients with anti-GBM antibodies had either cANCA or pANCA. In the second part of the study, the target antigens of ANCA were determined in Wegener's granulomatosis, microscopic polyarteritis, systemic vasculitis, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus (SLE). Of the 19 sera with cANCA, 13 (68%) were directed against proteinase 3; other antigens were myeloperoxidase (1 / 19, 5 %), elastase and lactoferrin together (1/19, 5%), lysozyme (1/19, 5%) or un
Journal of Clinical Pathology, 1999
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 diVerent 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.
The immunopathology of ANCA-associated vasculitis
2014
The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control.
Frontiers in Medicine, 2021
Aim Accumulating evidence supports the use of antineutrophil cytoplasmic antibody (ANCA) type to classify different clinical entities. We aimed to evaluate whether the presence and type of ANCA determine different diseases, based on clinical phenotypes, renal involvement, and response to treatment. Patients and Methods Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction ...