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D Vázquez-Abad

Publications and source records attributed to D Vázquez-Abad.

13 recordsLinked to original sources
PubMed1999

Anticentromere autoantibodies in patients without Raynaud's disease or systemic sclerosis.

Anticentromere autoantibodies (ACA) are associated with Raynaud's disease and systemic sclerosis (SSc). ACA usually bind at least one of three major centromere proteins (CENPs), particularly CENP-B. We identified 16 patients with ACA who do not have Raynaud's disease or SSc. The objective of this study was to determine whether these 16 ACA differ in antigenic specificity from the ACA found in patients with Raynaud's disease or SSc. Binding of these serum ACA was tested using competition experiments with recombinant CENP-B, and native centromere proteins from HEp-2 cells and HeLa nuclear extracts in ELISAs, immunoblots, and indirect immunofluorescence assays. The ACA from these 16 patients are strikingly different from those obtained from patients who have Raynaud's disease or SSc. Only 5 of the 16 index sera (31.25%) bound CENP-B from two or more different sources by at least two methods. Six of these 16 sera (37.5%) did not bind CENP-B on ELISA, and 8 of 16 (43.75%) did not bind CENP-B on immunoblots. Three sera did not bind CENP-B either by ELISA or immunoblots. Of the 13 sera that bound CENP-B, their patterns of binding to CENP-B strongly suggested that they bind different epitopes within the CENP-B antigen. Independently of their binding to CENP-B, these sera reacted mainly with minor CENP antigens detected by HeLa nuclear extracts. We have identified unusual ACA not associated with Raynaud's disease or SSc.

Adult↗
PubMed1997

Analysis of IgG subclasses of human antitopoisomerase I autoantibodies suggests chronic B cell stimulation.

Antitopoisomerase I autoantibodies are highly specific of scleroderma and are mainly IgG. The present study was designed to evaluate the prevalence of each IgG antitopoisomerase I subclass. An ELISA for the detection of IgG antitopoisomerase I subclasses was standardized and used to study the antibodies from 49 antitopoisomerase I-positive patients identified from a total of 541 patients. Correlations and multivariate analysis were performed to determine the frequency of associations between the IgG antitopoisomerase I subclasses. All IgG antitopoisomerase I subclasses were found. Twelve patients (24.5%) had all four IgG antitopoisomerase I subclasses, 13 (26.5%) had three, 16 (32.7%) had two, and 7 (14.3%) had only one antitopoisomerase I subclass. The presence of all four IgG antitopoisomerase I subclasses suggests that this specific B-cell is the target of multiple activation pathways which indicate that there is a complex T-cell-cytokine-driven process. Together with the absence of other autoantibodies in these sera, our results support the concept of a multiple but highly selected and chronic B-cell activation in scleroderma patients with antitopoisomerase I.

Adult↗
PubMed1997

A cross-reactive idiotype in scleroderma.

Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.

Animals↗
PubMed1996

Sensitivity and specificity of anti-Jo-1 antibodies in autoimmune diseases with myositis.

OBJECTIVE: To determine the sensitivity and specificity of anti-Jo-1 in systemic sclerosis (SSc) patients with and without myositis. METHODS: Immunoblots on HeLa nuclei were used to screen sera from 554 consecutive connective tissue disease patients. Those who had 45-55-kd bands, all patients with polymyositis/dermatomyositis (PM/DM), and a random selection of SSc, Raynaud's disease, systemic lupus erythematosus, and rheumatoid arthritis patients were also studied by anti-Jo-1 enzyme-linked immunosorbent assay and by immunoblots on rabbit pooled aminoacyl-transfer RNA synthetase. RESULTS: Anti-Jo-1 was present only in 8 of the 40 PM/DM patients. CONCLUSION: Anti-Jo-1 is specific for PM/DM.

Animals↗
PubMed1996

Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells).

The present study was designed to determine the subcellular localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells). Indirect immunofluorescence using commercial HEp-2 cells with human serum and human-affinity-purified anti-Jo-1 antibodies was performed using confocal microscopy. Anti-histidyl-tRNA-synthetase-positive sera showed distinct nuclear and cytoplasmic granular staining in HEp-2 cells. Affinity purified anti-Jo-1 produced an identical pattern to the whole serum, whereas the serum fraction that did not bind to the affinity column was negative by immunofluorescence on HEp-2 cells. Two commercial human anti-Jo-1-positive control sera and seven anti-Jo-1-positive sera from patients with myositis reproduced the nuclear and cytoplasmic granular pattern. We conclude that Jo-1 is present in cytoplasm and in intact nuclei from HEp-2 cells. The presence of tRNA synthetases in intact nuclei suggests that they have an unsuspected function in the nucleus.

Cell Nucleus↗
PubMed1996

Distinctive features of idiopathic inflammatory myopathies in French Canadians.

This is the first report on idiopathic inflammatory myopathies (IIM) in French Canadians. We reviewed retrospectively 30 French Canadian adults (20 women and 10 men) with IIM seen consecutively over 12 years. The median age at diagnosis was 45 years. The IIM were 8 (27%) primary polymyositis (PM), 9 (30%) primary dermatomyositis (DM), 5 (17%) IIM with neoplasia (lymphoma, breast, esophageal, colonic, and skin cancer) and 8 (27%) IIM with a connective tissue disease (4 with systemic sclerosis, 2 with mixed connective tissue disease, and 2 with rheumatoid arthritis). The most common presenting symptom was proximal muscle weakness (n = 10,33%). Of the remaining 20 patients, 6 (20%) had the onset of their weakness within 1 month of the presenting symptom. Only 3 (10%) patients did not have proximal muscle weakness. Twenty-six (87%) patients had weakness in the pelvic girdle, 25 (83%) in the shoulder girdle, and 7 (23%) in the neck muscles. Other common symptoms included dyspnea on exertion and dysphagia, each present in 13 (43%) patients. Gottron's papules and the heliotrope rash were the most common skin lesions documented in 11 (37%) and 10 (33%) patients, respectively. The serum creatine kinase (CK) level was between 171 and 1,000 U/L in 13 (43%) patients and between 1,001 and 6,000 U/L in 13 (43%) patients. Antinuclear antibodies (ANA) on HEp-2 cells were positive in 16 (53%) patients, of which 2 (13%) expressed autoantibodies to nuclear pore complexes. Autoantibody specificities were anti-La (n = 4, 13%), anti-U1RNP (n = 3, 10%), and anti-Ro (n = 2, 7%). None of the patients expressed anti-Jo-1, anti-topoisomerase I, or anticentromere antibodies. Twenty-eight (93%) patients received corticosteroid therapy, and 8 (27%) patients responded to prednisone alone. Thirteen (43%) patients were treated with methotrexate, and 9 (69%) responded. The mean follow-up was 62 months: 23 (77%) had their disease controlled, 3 (10%) patients were lost to follow-up, and 4 (13%) died (no death occurred because of IIM or its treatment). Therapy was discontinued because of remission in 5 (17%) patients. Cumulative survival rates at 2, 5, and 10 years were 89%, 89%, and 85%, respectively. The presence of autoantibodies to nuclear pore complexes and anti-La autoantibodies, the rare occurrence of anti-Jo-1 autoantibodies, the response to conventional therapies, and a high survival rate may distinguish IIM in French Canadians from that of other reported series.

Adult↗
PubMed1995

Longitudinal study of anticentromere and antitopoisomerase-I isotypes.

The isotypes of anti-CENP-B, the major anticentromere antibody (ACA), and antitopoisomerase I in patients with scleroderma and Raynaud's disease were studied longitudinally in order to determine whether there was evidence of isotype switch. One hundred and three sera samples from 13 ACA(+) patients and 6 antitopoisomerase I patients were studied over a period from 3 to 17 years. Anti-CENP-B was always IgG, whereas antitopo-I was IgG and IgA. IgM anti-CENP-B and IgM antitopoisomerase I, when present, were always found with IgG and/or IgA. Three patients developed IgG anti-CENP-B during the study. We conclude that anti-CENP-B and antitopoisomerase I show evidence of isotype switch with persistence of IgG expression which suggests a continued antigen-driven immune response.

Adult↗
PubMed1995

Autoantibodies in systemic sclerosis.

There are 3 major autoantibodies in sera from patients with scleroderma: 1) anticentromere antibodies (ACA), 2) anti-topoisomerase I (anti-topo I), and 3) anti-RNA polymerases. Each is present in about 25% of patients and are mutually exclusive. ACA are found in patients with primary and secondary Raynaud's disease and in patients with primary biliary cirrhosis. Anti-topo I and anti-RNA polymerases are found exclusively in scleroderma. Each autoantibody is present in specific subsets of scleroderma patients. ACA and anti-topo I have been well studied and their presence and titer are stable over time. The anti-topo I and ACA are of all three isotypes, recognize multiple epitopes on the antigens and have stable cross reactive or private idiotypes. The antigen, topoisomerase I, has domains which have homology to viral proteins. Other autoantibodies predominantly recognize nucleolar antigens, are found in less than 15% of patients, and are not specific for scleroderma.

Autoantibodies↗
PubMed1994

Anticentromere autoantibodies. Evaluation of an ELISA using recombinant fusion protein CENP-B as antigen.

OBJECTIVE: To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA). METHODS: Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B. RESULTS: Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively. CONCLUSION: The CENP-B ELISA is a sensitive and specific assay for ACA.

Antibodies↗
PubMed1989

Digital clubbing: a numerical assessment of the deformity.

We describe a simple method that defines with numbers the drumstick deformity of the digits. We measured 2 circumferences on each of the 10 fingers at the nail bed (NB) and at the distal interphalangeal joint (DIP), the sum of the 10 ratios NB:DIP was termed Digital Index. Intraobserver variation of the Digital Index was small, with a Pearson's correlation coefficient of R = 0.979; interobserver variation was also not significant (R = 0.999). Making use of this Digital Index, we studied 22 patients with digital clubbing associated with cyanotic congenital heart disease and 66 healthy controls. Digital Index clearly separated patients from controls, 10.73 +/- 0.32 vs 9.33 +/- 0.27 (means +/- SD). The Index was independent of age or sex. Patients with hypertrophic osteoarthropathy had significantly higher indices than patients with clubbing alone.

Adolescent↗
PubMedDate not supplied

Anti-endothelial cell antibodies in systemic sclerosis: significant association with vascular involvement and alveolo-capillary impairment.

OBJECTIVE: To assess the frequency of antiendothelial cell autoantibodies (AECAs) in a group of patients with systemic sclerosis (SSc) and possible associations with clinical and serologic features of the disease. METHODS: Sera from 50 patients with SSc (38 with the limited and 12 with the diffuse form) were screened for AECA (ELISA). The reference limits were were 56.6% for the IgM isotype and 3.3.5% for the IgG isotype. AECA results were analyzed in relation to lung involvement (chest x-ray, high resolution computed tomography (HRCT), ventilation scintiscan with radioaereosol (DTPA), pulmonary pressure (echodoppler technique): heart involvement (EKG, 24 hr ambulatory EKG, echocardiography), cutaneous involvement (skin score), capillaroscopic characteristics and digital ulcers. AECA were also correlated with the erythrocyte sedimentation rate (ESR), anticentromere (ACA) and antitopoisomerase I (ATA) autoantibodies, and angiotensin converting enzyme plasma levels (ACE). RESULTS: The AECA IgG prevalence was 40% (22/50) for the SSc group as a whole, without significant differences between subsets. A significant negative correlation was shown between the AECA and ACE plasma levels in both subsets. In the diffuse form, a significant positive correlation was found between AECA and ESR and significant associations were found between AECA and the parameters reflecting alveolo-capillary involvement (DLco, DTPA), the pulmonary artery pressures, digital ulcers and capillaroscopic abnormalities. No statistically significant correlations were found between AECA and heart involvement, the skin score or pulmonary interstitial fibrosis. CONCLUSIONS: These data suggest that in SSc the anti-endothelial cell antibodies are directly linked to vascular injury and could reflect endothelial damage. Further studies are needed to verify whether AECA might identify a subgroup of patients at higher risk for the development of vascular crises and whether they might therefore be considered a predictor of outcome in SSc patients.

Autoantibodies↗