Anti-beta 2-glycoprotein I antibodies and thrombosis.
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Biomedical subjects
Publications and source records attributed to Z Amoura.
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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.
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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.
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Collected samples serum of 30 MRL lpr/lpr and 15 MRL MP +/+ were tested by ELISA on purified mononucleosomes and its individual components, dsDNA and histones. Anti-mononucleosome antibodies can be detected as early as 10 and 23 week of age for MRL lpr/lpr and MP +/+, respectively, and arose before anti-dsDNA and anti-histone antibodies.
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.
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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.
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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.
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.
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OBJECTIVE: To study the prevalence and characteristics of arterial thromboembolic events (ATEE) in the course of AL amyloidosis. METHODS: We report the case of a non-anticoagulated patient with AL amyloidosis restrictive cardiomyopathy who developed acute lower limb ischaemia. We then prospectively determined the prevalence of ATEE in all patients with AL amyloidosis who were evaluated in our institution for autologous peripheral stem cell transplantation. RESULTS: Nine out of 15 non-anticoagulated patients (60%) developed ATEE: ischaemic stroke (3), transient cerebral ischaemic attack (2), multiple peripheral arterial emboli (1), bilateral iliac artery thrombosis (1), bilateral optic nerve ischaemia (1), and mesenteric ischaemia (1). Haemodynamic stasis seemed to play a leading role in the pathophysiology of ATEE, in that all patients were on sinus rhythm and only one had a thrombus on echocardiography. We identified possible contributing factors to ATEE occurrence: concomitant treatments with oestroprogestogen regimen, thalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and extracellular volume disturbances related to the cytapheresis procedure. CONCLUSION: We report on an unusual frequency of ATEE among patients with AL cardiac amyloidosis. Despite its theoretical risks, anticoagulation should be discussed for patients with amyloid cardiomyopathy.
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OBJECTIVE: Adult onset Still's disease (AOSD) is a systemic disorder with an uncertain outcome at the time of diagnosis. The clinical response to nonsteroidal antiinflammatory drugs (NSAIDs) is often unsatisfactory in adult patients. Chronic use of steroids is frequently required, but may result in severe side effects. We report the results of an uncontrolled, unblinded trial of intravenous immunoglobulin (IVIG) in 7 patients with AOSD. METHODS: Seven consecutive patients unresponsive or poorly responsive to NSAIDs were enrolled. None of them had received steroids previously. AOSD was defined by the Yamaguchi criteria (J Rheumatol 1992; 19: 424). IVIG were administered every 4 weeks. NSAIDs were initially maintained. A positive response was defined by the disappearance of fever and arthritis within 2 weeks after the first IVIG infusion. RESULTS: Two patients failed to respond. Five patients initially considered to be good responders were given a total of 4 to 6 IVIG infusions. One of them relapsed at the time of the fourth IVIG infusion. The four others had a favourable clinical and biological course. At the time of evaluation 3 patients were symptom-free and off therapy, while one was still receiving low dose NSAIDs. CONCLUSION: This short, uncontrolled, unblinded study suggests that IVIG might represent a potential alternative to classical steroid therapy in patients with AOSD refractory to NSAIDs. These preliminary results need to be confirmed, however, in a double-blind randomized study.