[Use of clinical tests to detect anti-neutrophil cytoplasmic antibodies in vasculitis].
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Antibodies, Antineutrophil Cytoplasmic↗
Biomedical subjects
A Wiik
Publications and source records attributed to A Wiik.
Heterogeneous nuclear ribonucleoproteins C1/C2 identified as autoantigens by biochemical and mass spectrometric methods.
The antigenic specificity of an unusual antinuclear antibody pattern in three patient sera was identified after separating HeLa-cell nuclear extracts by two-dimensional (2D) gel electrophoresis and localizing the antigens by immunoblotting with patient serum. Protein spots were excised from the 2D gel and their contents were analyzed by matrix-assisted laser desorption-ionization (MALDI) or nanoelectrospray ionization time-of-flight (TOF) tandem mass spectrometry (MS) after in-gel digestion with trypsin. A database search identified the proteins as the C1 and C2 heterogeneous nuclear ribonucleoproteins. The clinical spectrum of patients with these autoantibodies includes arthritis, psoriasis, myositis, and scleroderma. None of 59 patients with rheumatoid arthritis, 19 with polymyositis, 33 with scleroderma, and 10 with psoriatic arthritis had similar antibodies. High-resolution protein-separation methods and mass-spectrometric peptide mapping in combination with database searches are powerful tools in the identification of novel autoantigen specificities.
Adult↗
What you should know about PR3-ANCA. An introduction.
Anti-neutrophil cytoplasmic antibodies (ANCA) have become important diagnostic markers of small vessel vasculitides characterized by focal necrotizing lesions of vessel walls and accumulation of lymphocytes and macrophages around the affected vessels. IgG class ANCA directed to proteinase 3 (PR3) of neutrophils and monocytes seem to be directly involved in the pathophysiology of vascular damage by causing excessive neutrophil activation and vessel wall destruction. PR3 and elastase are important players in the mechanisms of vascular necrosis. Methods of detecting ANCA have now been defined but are not uniformly used, even though clinical decisions heavily depend on correct ANCA results.
Animals↗
[Pseudolymphoma and ventricular maltoma in patients with chronic gastritis, ulcer and Helicobacter pylori infection].
Among 128 patients with malignant B-lymphoproliferative disorders, 19 patients had long lasting dyspepsia and gastroscopy showed chronic active gastritis or gastric ulcer. PCR analysis for TCR and IgH clonality in biopsies showed local involvement of the malignant lymphocyte clone in four patients out of eight indicating presence of these cells in the inflammatory infiltrate. Weak B-cell clonality was found in four patients. A close relationship was seen between lymphocytic clonality and immune response to H. pylori Cag A, and all patients had parietal cell antibodies. Thus, the malignant clone may participate in the local inflammatory reaction, and continued local stimulation by H. pylori as well as parietal cell antigens may lead both to autoimmunity as well as a clonal development of lymphocytes.
Aged↗
Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features.
There have been a number of recent advances in this field. First, the "International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA)" has been developed to optimize ANCA testing. It requires that all sera are tested by indirect immunofluorescent (IIF) examination of normal peripheral blood neutrophils and, where there is positive fluorescence, in enzyme-linked immunosorbent assays (ELISAs) for antibodies against both proteinase 3 (PR3) and myeloperoxidase (MPO). Testing will be further improved when international standards and common ELISA units are available. Second, new diagnostic criteria for the small vessel vasculitides that take into account ANCA-positivity and target antigen specificity as well as histologic features are currently being produced. Third, we understand that the complications associated with treatment of the ANCA-associated vasculitides are often more hazardous than the underlying disease, and regimens that use effective but less toxic agents are being evaluated. The factors associated with increased risk of relapse, however, remain incompletely understood. Finally, ANCA with specificities other than PR3 and MPO are present in many nonvasculitic autoimmune diseases. Their clinical significance is still largely unclear, and some of the target antigens are present in other cells as well as neutrophils and thus are not strictly "ANCA."
Antibodies, Antineutrophil Cytoplasmic↗
Search for Borna disease virus in Danish fibromyalgia patients.
OBJECTIVE: The purpose of this study was to look for Borna disease virus (BDV) in 18 patients with acute onset of fibromyalgia (FMS) following a "flu-like" episode. BDV is a neurotropic RNA virus affecting horses and sheep. Infections in animals have been reported to cause immune mediated disease characterized by abnormalities in behavior. A possible link between BDV and neuropsychiatric diseases in man has been described, and lately a connection to chronic fatigue syndrome (CFS) has been suggested. METHODS: A BDV-specific nested PCR (RT-PCR) was performed on serum and spinal fluid. RESULTS: The BDV genome was not detected in any of the FMS cases. CONCLUSION: Although BDV was not demonstrated in spinal fluid or serum from the tested patients with FMS, we believe that it is important to report our results, since FMS can exhibit many manifestations in common with CFS. Possible reasons for the discrepant findings are discussed.
Adult↗
Characterisation of autoantibodies to neutrophil granule constituents among patients with reactive arthritis, rheumatoid arthritis, and ulcerative colitis.
OBJECTIVE: To study the frequency and distribution of antineutrophil cytoplasmic autoantibodies (ANCA) among patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and ulcerative colitis (UC) using different immunological methods. METHODS: Fifty serum samples from patients with reactive arthritis (26 with acute disease and 24 with chronic disease-that is disease of more than one year) were analysed for ANCA with indirect immunofluorescence, enzyme linked immunosorbent assay (ELISA) with six different neutrophil granule proteins as antigens, and immunoblotting on whole neutrophil extract and extracts of azurophil and specific granules. Thirty serum samples from patients with RA and UC served as controls in ELISA and indirect immunofluorescence. RESULTS: Sixteen per cent of patients with ReA were positive in immunofluorescence compared with 30% of patients with RA, and 70% of patients with UC. Thirty two per cent of patients with ReA were positive in ELISA. Antibodies directed against lactoferrin occurred in 20%, antibodies against bactericidal permeability increasing protein (BPI), elastase, cathepsin G, myeloperoxidase, and proteinase 3 were found in 8%, 2%, 2%, 8%, and 6%, respectively. Overall, 50% of RA sera and 53% of UC sera were positive in one or more ELISA assays, the corresponding figures for antibodies against individual antigens were for RA 7%, 3%, 0%, 13%, 47%, 17% and for UC 13%, 20%, 0%, 23%, 10%, and 17%. In immunoblotting, bands corresponding to lactoferrin and BPI were recognised in 44% and 22% of ReA sera. CONCLUSION: Antibodies against neutrophil granule antigens are often found in patients with ReA, primarily among those with chronic disease. The different methods detect various subsets of antibodies, with immunoblotting being the most and immunofluorescence the least sensitive.
Acute Disease↗
Determination of autoantibodies to annexin XI in systemic autoimmune diseases.
Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5/137), rheumatoid arthritis (1/21), and systemic lupus erythematosus (1/58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features. A relation between antibodies to annexins and thrombosis has so far only been known for annexin V.
Adult↗
Emerging concepts in the management of the malignant haematological disorders.
A comprehensive review of novel cytoreductive agents is presented. Such novel agents may be found among chemical compounds directed against specific molecular targets (cytostatics) or within the biological substances selectively aimed at the malignant clone (immunotherapy). It is stated that the purposes of immunotherapy in general are to generate a T-lymphocytic response against the tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system of the tumour-bearing host by DNA and/or RNA manipulation with subsequent interference with the signalling pathway in the tumour cells. Some immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene replacement therapy, suicide gene therapy, antisense oligonucleotides, alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most likely, a sequence of different treatment modalities will be used in the future comprising an initial debulking by means of standard chemotherapy and/or irradiation followed by target unspecific immunotherapy (polyclonal immunoglobulins, GvL effect etc.) and finally target specific elimination of residual tumour, probably with repeated use of the minimum effective pharmacologic dose (MEPD) of the agents used. In contrast, the current use of high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD) and associated severe organ toxicity, and high rates of secondary malignancies will probably be substituted in the future. An effective supportive treatment will be highly necessary, especially related to prevention and treatment of infections.
Antibodies, Monoclonal↗
[Scleroderma--systemic sclerosis. Serology, lung function and survival].
Patients with systemic sclerosis (SSc) were studied with regard to the presence of antinuclear antibodies (ANA) and their clinical correlates (n = 230), pulmonary function (n = 176), and mortality and causes of death (n = 344). ANA were found in 85%. Anti-centromere antibodies were found in 34%, anti-Scl-70 antibodies in 13% and anti-U1-RNP antibodies in 6.5%. These serological groups were associated with limited SSc, diffuse SSc, and myositis/arthritis, respectively. The most prevalent finding at first lung function test was isolated reduction of diffusion capacity (47%). Further deterioration of diffusion capacity was related to the presence of anti-centromere antibodies and increased sedimentation rate. The standardized mortality rate (SMR) was 2.9, higher in young patients (SMR = 13) and patients with diffuse SSc (SMR = 4.5).
Adolescent↗
Contamination of commercially purified myeloperoxidase preparations by lactoferrin.
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Antibodies, Antineutrophil Cytoplasmic↗
A critical evaluation of enzyme immunoassays for detection of antinuclear autoantibodies of defined specificities. I. Precision, sensitivity, and specificity.
OBJECTIVE: To determine the performance characteristics of enzyme-based immunoassay (EIA) kits for the detection of antinuclear and other autoantibodies of defined specificities. METHODS: Nine manufacturers of EIA kits to detect antibodies of defined specificities participated in a study in which they received coded sera from the Centers for Disease Control and Prevention. These coded sera contained different dilutions of antibody of one specificity mixed with sera containing antibodies of other specificities. The manufacturers were asked to use their standard technology to determine antibody content and send the data to a committee of the International Union of Immunological Societies for analysis. The data were analyzed for sensitivity and specificity in the detection of anti-double-stranded DNA (anti-dsDNA), anti-single-stranded DNA, antihistone, anti-Sm, anti-U1 RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 (DNA topoisomerase I), anticentromere, and anti-Jo-1 antibodies. In addition, replicate samples were included in the coded sera to evaluate the precision of each EIA method. RESULTS: Lack of sensitivity and specificity was most evident in the anti-dsDNA and anti-Sm kits, although 2 kits for anti-dsDNA achieved acceptable sensitivity and specificity. Generally, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, anticentromere, and anti-Jo-1 kits performed well. Many false-positive results were obtained with a multiple myeloma serum containing cryoprecipitates, but multiple myeloma sera without cryoprecipitates presented no problem in the EIA system. Precision, based on evaluation of replicate samples, varied from very good to poor. CONCLUSION: No single manufacturer was clearly superior to others in terms of their products' overall sensitivity, specificity, and precision. Areas that needed improvement were in kits for the detection of antibodies to dsDNA and to Sm antigen. Some EIA kits achieved good sensitivity and specificity. Individual manufacturers were informed of the performance of their respective kits so they could take measures to correct perceived deficiencies and thus improve the reliability of a group of important diagnostic assays used in the evaluation of systemic rheumatic diseases.
Antibodies, Antinuclear↗
Multicenter evaluation study on a new HEp2 ANA screening enzyme immune assay.
The COBAS Core HEp2 ANA enzyme immune assay (EIA) was evaluated in a precision and a clinical sample study in comparison to indirect immunofluorescence assay (IFA) on HEp2-cells. In the precision study the COBAS Core EIA yielded intraassay coefficient variations (CVs) mostly below 9%, and interassay CVs between 4.7% and 10.4%. When comparing the COBAS Core EIA to IFA, the results corresponded well in healthy subjects, systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis. In the case of Sjögren's syndrome and scleroderma patients the COBAS Core EIA yielded a lower rate of positive results compared to IFA. This discrepancy may be explained by the lack of detection of autoantibodies to nuclear antigens that can be identified only by IFA due to their compartmentalization and higher localized antigen density in HEp2 cells. The discrepancies in the group of dermato/polymyositis patients are due to the fact that the EIA contains mainly nuclear antigens and was able to detect only antibodies against the cytoplasmic Jo1 antigen that was added to the HEp2 nuclear extract. Routine sera were also evaluated; good agreement was found in sera from patients attending tertiary reference centres for autoimmune diseases but a higher number of discrepancies was reported in sera from unselected populations.
Adult↗
Autoantibodies to molecular targets in neutrophils in patients with ulcerative colitis.
Autoantibodies against neutrophil granulocytes are frequently observed in patients with ulcerative colitis, but a precise description of the autoantigens involved is lacking. Therefore, sera from 75 patients with ulcerative colitis were studied for antibody specificities by means of indirect immunofluorescence microscopy, enzyme-linked immunosorbent assays, and immunoblotting of extracts of neutrophils, neutrophil granules and lymphocytes. Fifty-six percent of the sera reacted in indirect immunofluorescence with ethanol-fixed neutrophils. On formalin-fixed cells most sera shifted fluorescence pattern, indicating a cytoplasmic origin of antigen(s). Only a few sera reacted with specific, known antigens. Immunoblots showed reactions with a broad panel of antigens with preferences for proteins around 55-65 kDa, which were present in azurophilic granules and in cytosol, an 80-kDa protein found in the specific granules, and a 110-kDa unknown cytosol component. In conclusion, neutrophil-specific IgG autoantibodies from ulcerative colitis patients react with several different antigens, most of which are of nonnuclear origin.
Autoantibodies↗
Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.
OBJECTIVE: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations. SUBJECTS AND DESIGN: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma. SETTING: A university hospital and The State Serum Institute in Copenhagen. INTERVENTION: Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non-infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M-components and monoclonal B-cell proliferation. MAIN OUTCOME MEASURES: Clinical and/or serological autoimmune manifestations, M-component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas. RESULTS: In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti-SSA and -SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations. CONCLUSIONS: To our knowledge this is the first systematic review of B-lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.
Aged↗
International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA)
Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in the primary systemic small vessel vasculitides. ANCA is best demonstrated in these diseases by using a combination of indirect immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). For ANCA testing in "new" patients, IIF must be performed on all serum samples. Serum samples containing ANCA, any other cytoplasmic fluorescence, or an antinuclear antibody (ANA) that results in homogeneous or peripheral nuclear fluorescence then should be tested in ELISAs for PR3-ANCA and MPO-ANCA. Optimally, ELISAs for PR3-ANCA and MPO-ANCA should be performed on all serum samples. Inclusion of the most recent positive sample in the IIF or ELISA may help demonstrate a change in antibody level. Reports should use recommended terms. Any report of positive neutrophil fluorescence issued before the ELISA results are available should indicate that positive fluorescence alone is not specific for the diagnosis of Wegener granulomatosis or microscopic polyangiitis and that decisions about treatment should not be based solely on the ANCA results.
Antibodies, Antineutrophil Cytoplasmic↗
Autoimmunity in Waldenström's macroglobulinaemia.
Fifty-seven consecutive patients with Waldenström's Macroglobuliemia were studied retrospectively for autoimmune manifestations. 28 patients or 51% (16 women and 13 men) had clinical and/or serological autoimmune manifestations, two or more of these being concomitant in 20 (12 women and 8 men). The predominant findings were Coombs' positive autoimmune hemolytic anemia (16%), seropositive rheumatoid arthritis (16%), inflammatory gastric ulcer with parietal cell autoantibodies (12%), and IgM-cardiolipin syndrome (11%). 40% of the autoimmune manifestations were present at the time of diagnosis of the Waldenström's Macroglobulinaemia and 60% were observed over a mean period of 4.7 years. All patients had an IgM M-component. There was no correlation between autoimmunity and the size of the M-component or the degree of hypo-IgG and hypo-IgA gammaglobulinemia. The only correlation between autoimmunity and infection was found in patients with gastric ulcer and parietal cell autoantibodies, in whom the infection was caused by Helicobacter pylori.
Aged↗
Distinct differences in autoantigen specificity of anti-neutrophil cytoplasm antibodies in systemic vasculitides and other inflammatory diseases.
BACKGROUND: Anti-neutrophil cytoplasm antibodies in necrotizing vasculitides need to be distinguished from ANCAs in other inflammatory conditions to avoid clinical misinterpretation. OBJECTIVES: To help clinicians and laboratory scientists recognize and utilize vasculitis-related ANCAs as an aid in diagnostic workup and patient follow-up, and be aware that ANCAs with different characteristics are commonly found in other chronic inflammatory conditions that persistently engage neutrophils in the inflammatory process. METHODS: Indirect immunofluorescence and enzyme immunoassay methods were used to detect ANCAs with both known and unknown neutrophil autoantigenic targets. RESULTS: Primary necrotizing small vessel vasculitides such as Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and renal-limited rapidly progressive necrotizing glomerulonephritis target either the serine protease proteinase 3 or myeloperoxidase in azurophilic granules. In ulcerative colitis and rheumatoid arthritis, we found multiple ANCA targets contained in azurophilic and specific granules, the cytosol and the nucleus, whereas PR3 and MPO were not, or only weakly, recognized. CONCLUSIONS: ANCAs typically found in active SVV are demonstrable both by indirect immunofluorescence and antigen-specific enzyme immunoassay, and strong reactivity to either PR3 or MPO is characteristic. Strong ANCA with MPO reactivity is also found in some patients with drug-induced syndromes (lupus, vasculitis). Intermediate to strong perinuclear ANCAs are found in a substantial proportion of patients with UC (40-60%) and RA (30-70%), but in these conditions the ANCAs have many antigen targets that are only weakly recognized.
Antibodies, Antineutrophil Cytoplasmic↗