Antineutrophil Cytoplasmic Antibodies (Anca): The Relationship Between Sex, Age and Antigenic Specificities (original) (raw)
Related papers
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
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.
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 & 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 -MPOsera showed the most varied reactivity to the minor antigens. Among the IF + groups, the IF + PR3 + /MPOsera 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.
Kidney International, 2000
Antineutrophil cytoplasmic antibodies and associated diseases: ternational Consensus Statement on Testing and Re-A review of the clinical and laboratory features. There have porting of ANCA" has been developed to optimize the been a number of recent advances in this field. First, the "Interusefulness of ANCA testing and to ensure more unifornational Consensus Statement on Testing and Reporting of mity in the laboratory results that are issued. It requires Antineutrophil Cytoplasmic Antibodies (ANCA)" has been developed to optimize ANCA testing. It requires that all sera that all sera should at least be tested by indirect immuare tested by indirect immunofluorescent (IIF) examination of nofluorescent (IIF) examination of normal peripheral normal peripheral blood neutrophils and, where there is posiblood neutrophils and, where there is positive fluotive fluorescence, in enzyme-linked immunosorbent assays rescence, in enzyme-linked immunosorbent assays (ELISAs) for antibodies against both proteinase 3 (PR3) and (ELISAs) for antibodies against proteinase 3 (PR3) and myeloperoxidase (MPO). Testing will be further improved when international standards and common ELISA units are myeloperoxidase (MPO). Testing could be further imavailable. Second, new diagnostic criteria for the small vessel proved by the development of international standards vasculitides that take into account ANCA-positivity and target and the adoption of common ELISA units. Current diagantigen specificity as well as histologic features are currently nostic criteria for the small vessel vasculitides do not take being produced. Third, we understand that the complications associated with treatment of the ANCA-associated vasculitides account of ANCA positivity or target antigen specificity, are often more hazardous than the underlying disease, and despite correlations with patterns of organ involvement regimens that use effective but less toxic agents are being and with the tendency to relapse. New criteria that inevaluated. The factors associated with increased risk of relapse, clude these features are now being developed by the however, remain incompletely understood. Finally, ANCA with specificities other than PR3 and MPO are present in many Chapel Hill group. "Overlap syndromes" in which there nonvasculitic autoimmune diseases. Their clinical significance is medium, as well as small vessel involvement, are recogis still largely unclear, and some of the target antigens are nized with increasing frequency. We have come to underpresent in other cells as well as neutrophils and thus are not stand that the ANCA-associated vasculitides are not instrictly "ANCA." variably fatal when treated appropriately and that the complications associated with relapses, especially in the older population, can be less hazardous than the therapy. The association of antineutrophil cytoplasmic antibod-Thus, regimens that use effective but less toxic agents ies (ANCA) with the small vessel vasculitides has proved are being actively sought. The risk factors for relapses helpful in the diagnosis and management of Wegener's in the ANCA-associated vasculitides and for the develgranulomatosis, microscopic polyangiitis, and Churgopment of generalized disease in Wegener's granuloma-Strauss syndrome, but the lack of technical guidelines tosis are incompletely understood at the present time. for antibody testing had meant that it was often difficult ANCA with specificities other than PR3 and MPO are to compare results from different laboratories. The "Infrequently demonstrated in patients with inflammatory bowel disease, autoimmune liver disease, rheumatoid
Clinical & Experimental Immunology, 2008
In view ofthe supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly ofthe IgGl and IgG4 subclass in all groups ofpatients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgGI levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgGl and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.