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Z Amoura

Publications and source records attributed to Z Amoura.

At least 19 recordsLinked to original sources
PubMed1996

Binding of nucleosomes to a cell surface receptor: redistribution and endocytosis in the presence of lupus antibodies.

In the present study, we sought evidence for a surface nucleosome receptor in the fibroblastic cell line CV-1, and questioned whether anti-double-stranded (ds) DNA and/or anti-histone autoantibodies could recognize and influence the fate of cell surface-bound nucleosomes. 125I-labeled mononucleosomes were shown to bind to the cell layer in a specific, concentration-dependent and a saturable manner. Scatchard analysis revealed the presence of two binding sites: a high-affinity site with a Kd of approximately 7nM and a low-affinity site (Kd approximately 400 nM) with a high capacity of 9 x 10(7) sites. Visualization of bound mononucleosomes by fluorescence revealed staining on both the cell surface and the extracellular matrix (ECM). Purified mononucleosome-derived ds DNA (180-200 bp) was found to complete for binding of 125I-mononucleosomes on the low-affinity site, to stain exclusively the ECM in immunofluorescence, and to precipitate three specific proteins of 43, 180 and 240 kDa from 125-I-labeled cell lysates. Nucleosomes were found to precipitate not only the 180-kDa ds DNA-reactive component, but also a unique protein of 50 kDa, suggesting that this protein is a cell surface receptor for nucleosomes on these fibroblasts. Once bound on the cell surface, mononucleosomes were recognized and secondarily complexed by lupus anti-ds DNA or anti-histone antibodies (i.e. anti-nucleosome antibodies), thus forming immune complexes in situ. The presence of these complexing auto-antibodies was found dramatically to enhance the kinetics of mononucleosome internalization. Following the internalization of the nucleosome-anti-nucleosome complexes by immunofluorescence, we observed the formation of vesicles at the edge of the cells by 5-10 min which moved toward the perinuclear region by 20-30 min. By means of double-fluorescence labeling and proteolytic treatment, these fluorescent vesicles were shown to be in the cytoplasm, suggesting true endocytosis of nucleosome-anti-nucleosome immune complexes. As shown by confocal microscopy, at no stage of this endocytic process was there any indication that coated pits or coated vesicles participated. Co-distribution of the endocytic vesicles with regions rich in actin filaments and inhibition of endocytosis of nucleosome-anti-nucleosome complexes by disruption of the microfilament network with cytochalasin D suggest a mechanism mediated by the cytoskeleton. Taken together, our data provide evidence for the presence of a surface nucleosome receptor. We also show that anti-ds DNA and anti-histone antibodies can form nucleosome-anti-nucleosome immune complexes in situ at the cell surface, and thus dramatically enhance the kinetics of nucleosome endocytosis.

Animals↗
PubMed1995

Presence of nucleosome-restricted antibodies in patients with systemic lupus erythematosus.

OBJECTIVE: To assess whether nucleosome-restricted antibodies, i.e., antibodies that react with the whole nucleosome particle but not with its individual components (double-stranded DNA [dsDNA] and histones), are present in the sera of patients with systemic lupus erythematosus (SLE). METHODS: Antibodies were detected by enzyme-linked immunosorbent assay using purified nucleosomes, dsDNA, or histones. These tests were applied to the sera of 40 patients with SLE. Protein G-purified IgGs of representative sera were sequentially adsorbed on dsDNA- and histone-conjugated solid-phase supports and further assayed for their nucleosome, dsDNA, and histone reactivities. RESULTS: Of the 40 sera tested, 16 displayed anti-dsDNA and/or antihistone antibody activity, which was always associated with significant antinucleosome reactivity. In addition, 3 sera showed antinucleosome activity that was not associated with concomitant anti-dsDNA or antihistone activity. The presence of true nucleosome-restricted antibodies was demonstrated, after solid-phase adsorption, in representative SLE sera that showed anti-dsDNA or antihistone antibody activity, and also in sera that did not show these activities. CONCLUSION: Our results provide evidence for the presence of nucleosome-restricted antibodies in patients with lupus. These nucleosome-restricted antibodies, along with anti-dsDNA and antihistone antibodies, appear to belong to a broad set of antinuclear antibodies, the antinucleosome family.

Adult↗
PubMed1994

Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria.

OBJECTIVE: To compare the humoral response to nucleosomes with the response to their individual components (double-stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice. METHODS: We used enzyme-linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones. RESULTS: Antinucleosome antibodies emerged before anti-dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome-restricted antibodies were detected in the proteinuric MRL mouse kidney eluate. CONCLUSION: Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.

Animals↗
PubMed1993

[Chronic diffuse interstitial pneumonia associated with chronic active hepatitis. 2 cases].

Two cases of chronic active hepatitis associated with diffuse interstitial pneumonia (lymphoid in one patient, lymphoid and fibrosing in the other) are reported. Histopathological data from the lungs, together with the parallel course of pulmonary and hepatic manifestations observed under corticosteroid therapy, suggest that these two diseases shared a common dysimmune pathogenesis. A few cases identical with these have been found in the literature. The clinical, laboratory and histopathological elements obtained from these cases also suggest an immune cause in most patients.

Adolescent↗
PubMed1992

Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus.

PURPOSE: Antiphospholipid antibodies (including anticardiolipin antibodies and circulating anticoagulant) are associated with thrombosis in systemic lupus erythematosus. Since it has been shown that beta 2 glycoprotein I (beta 2 gp I) acts as a cofactor of anticardiolipin antibody binding to cardiolipin, the presence and clinical meaning of anti-beta 2gp I antibodies in sera from patients with lupus were examined. PATIENTS AND METHODS: An enzyme-linked immunosorbent assay technique for the detection of anti-beta 2gp I antibodies was developed, and 47 lupus sera were studied retrospectively, as well as 88 healthy blood donors' sera. RESULTS: It was found that 17 of 47 patients with lupus (36%) had anti-beta 2gp I antibodies. Anti-beta 2gp I antibodies were statistically associated with anticardiolipin antibodies, thrombosis, and lupus anticoagulant. Eight of nine lupus patients with thrombosis had anti-beta 2gp I antibodies and lupus anticoagulant, and seven of them had anticardiolipin antibodies. Of 18 patients with anticardiolipin antibodies without anti-beta 2gp I antibodies or lupus anticoagulant, only one had thrombosis (due to nephrotic syndrome). Among anti-beta 2gp I-positive patients, 14 of 16 had lupus anticoagulant activity, whereas only three patients with lupus anticoagulant were anti-beta 2gp I-negative. CONCLUSIONS: The presence of anti-beta 2gp I antibodies is a new immunologic feature of lupus patients with thrombosis. In addition, since anti-beta 2gp I antibodies are closely associated with lupus anticoagulant activity, they may contribute to explain antiprothrombinase activity.

Autoantibodies↗
PubMed1991

[Anti-beta 2 glycoprotein I antibodies in systemic lupus erythematosus: a marker of thrombosis associated with a circulating anticoagulant].

An ELISA technique for the detection of anti-beta 2 glycoprotein I (beta 2gp I) antibodies was developed. Among 47 systemic lupus erythematosus patients, 17 had anti-beta 2gp I antibodies. These antibodies were statistically associated with anticardiolipin antibodies, lupus anticoagulant and thrombosis. Out of 18 patients with anticardiolipin antibodies without anti-beta 2gp I antibodies or lupus anticoagulant, only one had thrombosis (due to nephrotic syndrome). Therefore the presence of anti-beta 2gp I antibodies is a new immunologic marker of lupus patients with thrombosis. In addition, we propose that anti-beta 2gp I antibodies may be directly responsible for lupus anticoagulant activity.

Antibodies↗
PubMed1990

[Treatment of systemic diseases with pulse cyclophosphamide: 15 cases].

Fifteen patients suffering from severe systemic diseases were treated with monthly pulses administration of cyclophosphamide (0.7 g/m2 of body surface): 8 acute systemic lupus erythematosus, 2 Wegener's granulomatous, 1 polyarteritis nodosa, 1 rheumatoid vasculitis, 1 progressive systemic sclerosis, 1 relapsing uveitis and 1 dermatopolymyositis. The indications for cyclophosphamide were: glomerulonephritis (6 cases), resistance to previous treatments (7 cases) and undesirable side effects of corticosteroid therapy (2 cases). After 3 pulses, the disease was controlled in 12 patients (80%) and corticosteroids could be decreased in all 12 cases without an evolutive relapse of the disease. Five patients developed infections (2 septicemia, 1 zona, 1 herpes gingival stomatitis and 1 viral meningitis) which were treated without sequelae. One patient developed cystitis with hematuria after the 3rd pulse; association of mesna, a urinary tract protective agent, enabled the continuation of treatment without a cystitis relapse. At the end of our retrospective study, the efficacy of pulse cyclophosphamide administration seems to be satisfactory but the risk of undesirable side effects should limit its use to severe systemic diseases or those resistant to conventional therapies.

Adult↗
PubMed1990

Treatment of progressive systemic sclerosis by plasma exchange: long-term results in 40 patients.

The efficacy of plasma exchanges (PE) during the course of scleroderma has only been investigated for short periods. The aim of this study was to follow patients over a long enough period to observe the course of the clinical and paraclinical symptoms in the short, medium, and long term. Forty patients, 24 women and 16 men, were treated by PE and observed for 1-3, 3-12 and over 12 months. Immunological, biological and clinical course and any undesirable side effects were evaluated using a detailed questionnaire. Concomitant therapies were reported and most frequently consisted of corticosteroids, colchicine, factor XIII or vasodilators (nifedipine, captopril). The therapeutic effectiveness of PE was assessed on the basis of improvements in cutaneous, digestive, joint, muscular, lung, cardiovascular and renal lesions. Our findings confirmed the effectiveness of short-term PE on scleroderma (52% of the patients improved during the first 3 months). However, this improvement was transient (5% improvement between 3 and 12 months and only 2.5% over 12 months) and limited to the cutaneous and muscular lesions. Thus, PE cannot be recommended for the treatment of progressive systemic sclerosis.

Adolescent↗
PubMed1989

[Plasma exchange].

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Autoimmune Diseases↗