Biomedical subjects

A Wiik

Publications and source records attributed to A Wiik.

At least 55 records · Page 3Linked to original sources

PubMed1998

Essential fatty acid status in cell membranes and plasma of patients with primary Sjogren's syndrome. Correlations to clinical and immunologic variables using a new model for classification and assessment of disease manifestations.

In 41 primary Sjögren's syndrome patients we compared fatty acid levels within erythrocyte phospholipids, plasma phospholipids, plasma triglycerides and plasma cholesterol esters, with the immunopathological and clinical disease status. Docosahexaenoic acid was the essential fatty acid (EFA), the levels of which correlated (inversely) most closely with the clinical disease status (r=-0.33 to -0.50). Levels of dihomogammalinolenic acid and eicosapentaenoic acid correlated inversely to levels of IgM rheumatoid factors (r=-0.33) and anti-SSA/Ro antibodies (r=-0.40) respectively. Moreover, levels of anti-SSA/Ro antibodies (r=-0.34-0.40) correlated with levels of the proinflammatory arachidonic acid. Sigma n-3 EFA/sigma n-6 EFA ratios correlated significantly to the quantitative estimates of immunopathological and clinical disease status. Our data are in agreement with current understanding of pro- and anti-immunoinflammatory roles within EFA metabolism, and support the rationale for intervention studies.

8,11,14-Eicosatrienoic Acid↗

PubMed1998

Lower leg electrical impedance after distal bypass surgery.

Electrical impedance was determined in 13 patients following distal bypass surgery to evaluate lower leg oedema as reflected by its circumference. Tissue injury was assessed by the plasma concentration of muscle enzymes. After surgery, the volume of the control lower leg increased from 1250 (816-2373) to 1384 (874-2345) ml (median and range; P < 0.05), where the impedance did not change significantly from 140 (92-181) ohms. The volume of the operated leg increased more [from 1129 (824-2373) to 1600 (1090-2837) ml], and the decrease in electrical impedance was also pronounced [137 (125-169) to 83 (69-104) ohms (P < 0.001)]. Tissue injury after surgery was indicated by an increase in total creatine kinase (n = 17) and MB isoenzyme of creatine kinase (n = 8) (P < 0.05). Myoglobin (n = 8) had increased already during surgery (P < 0.05), whereas there was no significant change in the plasma concentration of troponin I (n = 8). In conclusion, tissue injury was reflected by increases in muscle enzymes in plasma. We found an inverse correlation between lower leg electrical impedance and volume, but the deviation in electrical impedance was approximately twice that of the leg volume. Electrical impedance appears to be a useful method for the evaluation of lower leg oedema after distal bypass surgery.

Adult↗

PubMed1998

Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization.

Anti-neutrophil cytoplasmic antibodies (ANCA) are widely used as diagnostic markers for Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and idiopathic rapidly progressive glomerulonephritis (iRPGN). The objective of this study was to evaluate the diagnostic value of ANCA measurement by the indirect immunofluorescence (IIF) test, and by anti-PR3 and anti-MPO ELISA performed in different locations, in patients with idiopathic small vessel vasculitis. Fourteen centers participated in a standardization study of ANCA assays, and entered a total number of 169 newly diagnosed and 189 historical patients with idiopathic systemic vasculitis or iRPGN. Patients were classified according to a pre-defined diagnostic classification system. Results were compared with those of 184 disease controls and 740 healthy controls. The IIF test was performed according to standard methodology; ELISAs had been standardized among the participants in a previous phase of the study. The sensitivities of assays in patients were as follows. The sensitivity in WG was: cANCA 64%, pANCA 21%, anti-PR3 66%, anti-MPO 24%. In MPA the sensitivity was: cANCA 23%, pANCA 58%, anti-PR3 26%, anti-MPO 58%. Sensitivity in iRPGN was: cANCA 36%, pANCA 45%, anti-PR3 50%, anti-MPO 64%. The specificity of assays (related to disease controls) was: cANCA 95%, pANCA 81%, anti-PR3 87%, anti-MPO 91%. When the results of the IIF test were combined with those of the ELISAs (cANCA/anti-PR3 positive, pANCA/anti-MPO positive), the diagnostic specificity increased to 99%. The sensitivity of the combination of cANCA + anti-PR3 or pANCA + anti-MPO for WG, MPA or iRPGN was 73%, 67% and 82%, respectively. From this study we conclude that the value of the IIF test for ANCA detection can be greatly increased by the addition of a well standardized antigen-specific ELISA. In a significant number of patients with idiopathic small vessel vasculitis, however, the ANCA test results (either in IIF or ELISA) are negative.

Adolescent↗

PubMed1998

Clinical evaluation of a capture ELISA for detection of proteinase-3 antineutrophil cytoplasmic antibody.

Detection of antineutrophil cytoplasmic antibodies (ANCA) has become a useful tool in the diagnosis of Wegener's granulomatosis and microscopic polyangiitis. However, the results obtained with indirect immunofluorescence (IIF) and by ELISA for ANCA demonstration do not always correlate. A possible explanation for this finding could be that proteins are denatured during the process of antigen purification or during coating onto the solid phase. To avoid this possibility, a monoclonal antibody to PR3 that is precoated on the plate can be used. In the present study we have used the monoclonal antibody (MoAb) 4A3 for the capture of PR3 in an ELISA, and a clinical evaluation of the diagnostic properties of the new capture ELISA has been made. The sensitivity of the capture PR3-ANCA ELISA was 85% in a material of c-ANCA positive sera. A specificity of 90% was obtained in analyses from patients having various forms of glomerulonephritis. There was a significantly higher diagnostic sensitivity of the capture PR3-ANCA ELISA (85%) compared to c-ANCA by IIF (58%) in patients with Wegener's granulomatosis with renal involvement. Capture PR3-ANCA and direct ELISA for MPO-ANCA together gave a diagnostic sensitivity of 98%, versus 75% using IIF. In conclusion, the capture PR3-ANCA ELISA seems to be a valuable tool in the diagnosis of Wegener's granulomatosis with renal involvement. Preliminary data suggest that the technique may have an advantage over direct ELISA for PR3-ANCA, as well as in the follow-up of c-/PR3-ANCA associated vasculitides. However, further prospective studies are needed to clarify this premise.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1998

Characterization of murine monoclonal anti-endothelial cell antibodies (AECA) produced by idiotypic manipulation with human AECA.

The IgG fraction of human anti-endothelial cell antibodies (AECA) obtained from a patient with Wegener's granulomatosis was used as immunogen to raise AECA mAb in mice selected among those which developed vasculitis-like lesions after immunization. Three mAb (BGM, 3C8 and 7G2), selected by cyto-ELISA and flow cytometry analyses, featured a specific reactivity with human umbilical vein endothelial cells (HUVEC) and the mouse endothelial cell line H5V; on the contrary, HEp2 cells, the murine melanoma B16 cell line, the extracellular matrix as well as several other antigens tested were not recognized. BGM mAb, an IgG3 precipitating a 70 kDa structure from HUVEC, was able to induce endothelial cells to secrete amounts of IL-6 significantly higher than irrelevant controls or mAb binding different endothelial antigens (i.e. CD31, CD29, ICAM-1 and HLA class I). BGM mAb induced significant levels of antibody-dependent cell cytotoxicity (13 +/- 2.5 versus 0.6 +/- 0.03%). To the best of our knowledge, BGM is the first murine mAb specific for human endothelial cells generated by idiotypic manipulation; secondly, its biological properties further support the notion of a pathogenic role for AECA in autoimmune-mediated diseases.

Animals↗

PubMed1998

Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis.

The objective was to investigate the relationship between the presence of different types of antinuclear antibodies (ANA) in patients with systemic sclerosis (SSc) and the presence of clinical features. Sera from 230 patients with SSc were tested for the presence of ANA, including anticentromere antibodies (ab), antitopoisomerase I ab, anti-U1 RNP ab and antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP. Clinical features were registered prospectively in a clinical database. Eighty-two per cent of the patients were women. The median age was 58 yr (45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA were found in 86% of the patients (anticentromere: 34%; antitopoisomerase I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%; anti-U3 RNP: 3.5%; anti-U17 RNP: 0%). Anticentromere ab were found to be related to a high prevalence of calcinosis, telangiectasia, digital ulcers, acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary diffusing capacity, and a low prevalence of radiological evidence of pulmonary fibrosis. Antitopoisomerase I ab were associated with a high prevalence of digital joint deformity, distal osteolysis, radiological signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis and myositis, a low prevalence of calcinosis, and early disease onset. The presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was not significantly related to any particular clinical features in this study; possibly due to the small number of patients with these ab. The presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the serum was also found to have previously described clinical correlations in a group of Danish SSc patients.

Adolescent↗

PubMed1997

A simple high yield procedure for purification of human proteinase 3, the main molecular target of cANCA.

Proteinase 3, the antigen commonly recognized by classical anti-neutrophil cytoplasmic antibodies (cANCA) in patients with Wegener's granulomatosis was purified from neutrophil azurophilic granules. Proteinase 3, a serine protease with an apparent molecular mass of 29 kDa, was extracted with Triton X-100 from the azurophilic granule fraction of neutrophils after nitrogen bomb cavitation and Percoll gradient centrifugation. Anion exchange chromatography removed many proteins, which were bound to the column. The unbound proteins, which contained most of the proteinase 3, were then separated by gel filtration. All chromatography steps were done in the presence of detergent. SDS polyacrylamide gel electrophoresis of this preparation only revealed three bands migrating closely together at the position of a 29-31 kDa protein, characteristic of proteinase 3. Affinity-purified polyclonal antibodies raised against proteinase 3 were used for immunoblotting studies and demonstrated that the purified protein was proteinase 3. Antibodies to elastase, cathepsin G, myeloperoxidase, lactoferrin or lysozyme did not react in ELISA assays with the isolated protein. The proteinase 3 prepared by this procedure was found to be suitable as an antigen for detecting PR3-ANCA both in ELISA and in immunoblotting experiments.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1997

Range of antinuclear antibodies in "healthy" individuals.

OBJECTIVE: To determine the range of antinuclear antibodies (ANA) in "healthy" individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). METHODS: Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reflect the output of a cross-section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. RESULTS: In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20-60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. CONCLUSION: It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.

Adult↗

PubMed1997

Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T lymphocytes to extracellular matrix proteins.

Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can activate neutrophils to adhere to endothelium, degranulate, and cause endothelial cell injury. These data have lead to the hypothesis that the T cell inflammatory response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to stimulation of neutrophils by ANCA. So far there is no evidence for a direct effect of ANCA on lymphocytes. The present study was designed to examine whether lymphocytes can be directly stimulated by ANCA to adhere to endothelial extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes to fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG containing ANCA or control human IgG, respectively; P = 0.0045). The same induction of adhesion to fibronectin, laminin, and intact ECM was observed when the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG. Similarly, ANCA-enriched IgG produced in mice increased the adhesion of lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endothelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to ECM.

Animals↗

PubMed1997

A longitudinal study of pulmonary function in Danish patients with systemic sclerosis.

OBJECTIVE: To determine the types, prevalence and development of respiratory abnormalities in patients with systemic sclerosis (SSc), and to correlate the results with clinical and serological findings. METHODS: 176 patients with SSc observed longitudinally were retrospectively included in the study. The change per year of vital capacity (VC), forced expiratory volume in one second/vital capacity (FEV1/VC), diffusing capacity (DLco) and diffusing constant (Kco) of carbon monoxide from the first till the latest pulmonary function test were correlated to clinical and serological findings, including anti-centromere, anti-Scl-70, and antinucleolar antibodies. RESULTS: An isolated reduction of DLco was seen in 47% and a restrictive ventilatory pattern in 25% of the patients. Restrictive ventilatory pattern correlated to pulmonary fibrosis, dyspnoea, a low prevalence (13%) of anti-centromere antibodies and a high prevalence of anti-Scl-70 antibodies (36%). Progression of DLco reduction was related to long disease duration, presence of anti-centromere antibodies and absence of treatment with penicillamine. CONCLUSION: Pulmonary involvement is common in patients with SSc. The occurrence of different serological abnormalities in patients with restrictive disease and in patients with progressive isolated reduction of DLco, suggests that the two types of pulmonary damage may have different pathogeneses rather than being different stages in the progression of pulmonary damage.

Adult↗

PubMed1997

The frequency of autoantibodies in Turkish patients with lupus nephritis.

We analysed the frequency of autoantibodies in 44 patients with lupus nephritis. Antinuclear antibody (ANA) was found in 91% of patients by an indirect immunofluorescence technique on HEp-2 cells at the time of study. Anti-dsDNA antibodies were found at high levels in most of the patients using the SynELISA test, which reveals both high and low avidity antibodies, but only in 64% of patients using the DAKO assay, which reveals high avidity antibodies. Anti-histone antibodies were found in 52% of the patients. Anti-SSA/Ro antibodies were positive in 27% of all patients; these patients also had prominent cutaneous involvement and photosensitivity. The frequency of anti-SSB/La and Anti-Sm antibodies was 7%. Immunoblotting experiments confirmed the findings shown by the techniques described above, and anti-ribosomal antibodies were found to be positive in more cases by the latter assay. IgA rheumatoid factor (RF) was more frequent (20.4%) than IgM RF (9.9%). In conclusion, Turkish patients suffering from lupus nephritis seem to express a total autoantibody profile similar to that reported for systemic lupus erythematosus from other parts of Europe.

Adolescent↗

PubMed1997

Antibodies to cardiolipin may increase the risk of failure of peripheral vein bypasses.

OBJECTIVES: To assess the association between antibodies to cardiolipin and infrainguinal vein graft patency. MATERIALS AND METHODS: Plasma levels of antibodies to cardiolipin, haemostatic factors, lipids and the smoking marker carboxyhaemoglobin were determined preoperatively and 6 weeks postoperatively in 80 patients undergoing infrainguinal vein bypass surgery. Bypass patency was assessed by ankle blood pressure measurements and ultrasound duplex scanning at 1 week, 6 weeks, 3, 6, 9 and 12 months. A localised increase in the graft peak systolic velocity by a factor of 2.5 or more was considered to indicate a significant stenosis. RESULTS: Antibodies to cardiolipin were identified in seven (9%) patients preoperatively. In four of these seven patients the bypasses thrombosed within 3 months after surgery and another two developed stenoses. At 6 months the primary bypass patency, i.e. patency without stenosis, was 14% (95% confidence interval (CI) 0-33%) in patients with antibodies to cardiolipin, as opposed to 57% (95% CI 45-69%) in patients without these antibodies (log rank test: p = 0.03). Diabetes mellitus was also associated with a reduced 6 months primary bypass patency (38% (95% CI 16-60%) vs. 58% (95% CI 45-71%), p = 0.006). A Cox regression analysis showed that both the presence of antibodies to cardiolipin and diabetes independently contributed towards predicting the overall risk of bypass failure. CONCLUSION: Antibodies to cardiolipin were identified in 9% of patients undergoing infrainguinal vein bypass surgery and appeared to be associated with increased risk of bypass failure.

Aged↗

PubMed1997

Rapid screening assay for anti-GBM antibody and ANCAs; an important tool for the differential diagnosis of pulmonary renal syndromes.

BACKGROUND: Pulmonary renal syndrome is encountered in several diseases such as Goodpasture's syndrome, antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis, systemic lupus erythematosus (SLE) and infection-associated or drug-induced glomerulonephritis. To preserve organ function it is of vital importance to make the correct diagnosis and institute adequate therapy early, in the acute phase. METHOD: An enzyme-linked immunosorbent assay (ELISA), specially designed as a rapid screening assay for antiglomerular basement membrane (anti-GBM) antibody, proteinase-3 (PR3-) ANCA and myeloperoxidase-(MPO-) ANCA were evaluated from 1060 serum samples drawn from patients with clinically suspected pulmonary renal syndrome or rapidly progressive glomerulonephritis (RPGN). RESULTS: Of the 1060 serum samples, 142 were positive for anti-GBM antibody (n = 19), PR3-ANCA (n = 60), or MPO-ANCA (n = 73). Of the 142 samples, 10 were double positive. Reanalysis of positive sera with a quantitative ELISA yielded results manifesting good correlation with those of the the rapid screening assay. Of 918 sera found to be negative in the rapid screening assay, 105 were also tested with IIF, 11 being found to be positive. However, these 11 sera manifested no specificity for PR3 or MPO, but some were specific for bactericidal/permeability-increasing proteins, lactoferrin or elastase ANCAs. Two of the patients whose sera yielded negative results in the rapid assay had systemic vasculitis. CONCLUSION: The ELISA thus detects the true antibodies to PR3, MPO, and GBM, whereas IIF detects additional specificities. The findings suggest the rapid assay results to be of high positive predictive value, and the assay to be of high diagnostic specificity and sensitivity and thus useful in the diagnostic workup in suspected cases of RPGN or pulmonary renal syndrome.

Anti-Glomerular Basement Membrane Disease↗

PubMed1997

Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA).

The objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins and by immunoblotting of electrophoretically separated cell, granule or nuclear extracts. Forty-two sera (68%) reacted with ethanol-fixed neutrophils. In the ELISAs 32% of the 28 medium to strongly IIF-positive sera were negative, while 43% were weakly positive for more than one antigen. Immunoblots of whole neutrophils showed IgG reactions at 25-35 kD, in the 55-kD region, at 80 kD, and at 110 kD. Most sera reacted with more than one band. Except for the 55-kD antigen, none of the antigens appeared in lymphocytes. The most notable reactivity in subcellular fractions was with lactoferrin and with bands of 25-35 kD from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactoferrin is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved.

Adult↗

PubMed1997

Quantitative assessment of clinical disease status in primary Sjögren's syndrome. A cross-sectional study using a new classification model.

Quantitative and qualitative assessment of the clinical disease manifestations in 41 primary Sjögren's syndrome (pSS) patients was performed according to a new classification model. Frequencies of subgrouped disease manifestations were as follows: 1) surface exocrine disease: 100%, 2) internal organ exocrine disease: 63%, 3) monoclonal B lymphocyte disease: 5%, 4) inflammatory vascular disease: 71%, 5) non-inflammatory vascular disease: 59%, 6) mediator induced disease: 98%. Summary scores for severity of surface exocrine disease correlated to the summary scores of all other disease manifestations (p = 0.02), to the summary scores of internal organ exocrine disease (p = 0.003), and to the summary scores of mediator induced disease (p = 0.03). Blood leucocyte counts showed significant negative correlations to levels of plasma IgG, serum IgA-RF, IgM-RF, anti-SSA/SSB antibodies, IL-6, and IL-1Ra. We conclude that the model made detailed analysis of the clinical presentation of pSS possible, and thus may assist in elucidating important pathobiological aspect of the disease.

Adult↗

PubMed1996

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays.

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1996

Follow-up of 151 patients with high-titer U1RNP antibodies.

We performed a longitudinal follow-up study of clinical findings in 151 patients with high-titer antibodies against U1 ribonucleoprotein (U1RNP) as measured by haemagglutination. Formal connective tissue disease (CTD) diagnoses were assigned and diagnostic transitions analysed. One-hundred eighteen females and 33 males entered the study; the mean duration of follow-up was 7.1 years. Mean age at entry was 34.7 years; 73% of the patients had early disease (duration < 2 years). Fifty-six patients (37%) presented with a definite diagnosis, most often mixed connective tissue disease (MCTD, n = 40), followed by systemic lupus erythematosus (SLE, n = 11) and systemic sclerosis (SSc, n = 5). Of 84 patients (56%) presenting with nonspecific symptoms of possible, "undifferentiated" CTD, 58 developed MCTD, 4 SSc and 2 SLE. By the end of the follow-up period. 127 patients had developed a well-defined CTD; final diagnoses were: MCTD (n = 97), SLE (n = 18), SSc (n = 12). We conclude that CTD in the context of high-titer anti-U1RNP antibodies may be transitive and sequential in nature, although the diagnostic criteria for MCTD previously proposed by our group seem to delimit a clinically stable condition in most patients in this subgroup.

Adolescent↗

PubMed1996

Complexes between proteinase 3, alpha 1-antitrypsin and proteinase 3 anti-neutrophil cytoplasm autoantibodies: a comparison between alpha 1-antitrypsin PiZ allele carriers and non-carriers with Wegener's granulomatosis.

To test the hypothesis that anti-neutrophil cytoplasm autoantibodies (ANCAs) interfere with the functions of proteinase 3 (PR3) (the Wegener autoantigen) and alpha 1-antitrypsin (alpha 1AT), complexes of PR3/alpha 1 AT and PR3/PR3-ANCA-IgG were assayed Plasma samples were obtained from 44 patients with Wegener's granulomatosis (WG): 34 had active disease (88% ANCA positive) whereas 10 patients were in remission (20% ANCA positive). Plasma samples from 14 of the patients with active disease were also available at the time of remission. The complexes of PR3/alpha 1 AT and PR3/PR3-ANCA-IgG were detected by capture enzyme-linked immunoassays (ELISAs) alpha 1 AT deficiency was evaluated by determining PiZ alleles by ELISA. Eight (18%) of the patients were PiZ positive. The frequency of this alpha 1-antitrypsin phenotype in the Scandinavian population is 4.7% (P < 0.001). The median PR3/alpha 1AT complex level in the PiZ-positive group with active disease (n = 5) was similar to the level in the PiZ-negative group with active disease. During remission the median level for the PR3/alpha 1AT complex was significantly higher than in the acute group (P < 0.001) including both PiZ-positive and PiZ-negative patients. No difference between PiZ positivity and PiZ negativity could be found in the remission group. PR3/PR3-ANCA-IgG complexes were found in patients with acute disease as well as in patients in remission, in almost equal frequency. This complex was also present in 13/18 ANCA-negative samples from patients in remission. Finally, purified IgG fractions from WG patients were examined for their capacity to inhibit binding between PR3 and alpha 1AT. An effect on the binding between PR3 and alpha 1AT by PR3-ANCA could not be demonstrated. Thus, our results do not support the hypothesis that PR3-ANCA interferes with the binding between PR3 and alpha 1AT. However, the high prevalence of the PiZ alleles among WG patients suggests that an imbalance between proteinases and alpha 1AT may be of importance in this disease. The clinical usefulness of both the PR3/alpha 1AT and the PR3/PR3-ANCA-IgG complexes and the possible influence on ANCA detection need to be examined in prospective longitudinal studies.

Acute Disease↗