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Biomedical subjects

Z Amoura

Publications and source records attributed to Z Amoura.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Biopathology of disseminated lupus erythematosus].

Systemic lupus erythematosus is associated with a plethora of immunological abnormalities. First, there are antinuclear autoantibodies directed towards insoluble (mainly desoxyribonucleic acid, histones and nucleosomes) or soluble nuclear components (mainly Sm, RNP and Ro/SSA particles). There are then autoantibodies other than antinuclear, recognizing cells (erythrocytes, lymphocytes, neutrophils, endothelial cells), organelles (Golgi apparatus, ribosomes) or molecules (cardiolipids, C1q, stress proteins). Finally, there are immunological abnormalities other than autoantibodies, such as immune complexes, monoclonal immunoglobulins or complement variations. In fact the pathogenetic role of these perturbations remains a matter for speculation.

Antibodies, Anticardiolipin↗
PubMed1998

Early anti-nucleosome autoantibodies from a single MRL+/+ mouse: fine specificity, V gene structure and pathogenicity.

In systemic lupus erythematosus, the nucleosome assumes a central role in the autoimmune response to self antigens. To gain insight into the etiology and pathogenesis of anti-nucleosome antibodies (Ab), we analyzed a panel of six IgG-secreting hybridomas derived from a single young MRL +/+ mouse at the onset of the autoimmune response. All monoclonal antibodies (mAb) bound exclusively the native nucleosome, and represented five different clonotypes that recognized diverse nucleosomal epitopes, typical of a polyclonal response. The VH-complementarity-determining region (CDR)3 regions exhibited unique stretches of charged amino acids with different polarity that may be important for the interaction with the nucleosome. These early anti-nucleosome mAb displayed striking structural differences with not only anti-DNA, but also with anti-nucleosome Ab, that appear later in disease. Two of the mAb deposited in kidney glomeruli after in vivo administration to RAG-1-deficient mice, suggesting that diverse B cell clones, possibly selected by the nucleosome itself, may play a role in the initiation of kidney damage.

Amino Acid Sequence↗
PubMed1998

[Infectious aneurysm due to Listeria monocytogenes: a new case and review of the literature].

INTRODUCTION: Infections due to Listeria monocytogenes usually occur in pregnant women, in the elderly and in immunocompromised patients. Arterial aneurysms due to this germ are rare. Only 16 cases have been previously described in the literature. EXEGESIS: We report the case of a patient who had been hospitalized for recurrent fever over the past 3 months. Aortic mycotic aneurysm was diagnosed; blood and aneurysm cultures revealed Gram-positive bacilli consistent with the presence of Listeria monocytogenes. We also review previous reports focusing on infections due to Listeria monocytogenes. Mycotic aneurysms due to this germ are mainly observed in elderly male patients and occur on large arteries. In the present study, only one patient was immunocompromised. Furthermore, all patients who were not operated on died. CONCLUSION: Arterial aneurysm due to Listeria moncytogenes is best managed via surgical resection in combination with antimicrobial therapy. Immunosuppression is not necessary for the development of arterial aneurysm due to Listeria. Bacteriological and histological examinations should be done systematically when surgical resection of an aneurysm is required.

Aged↗
PubMed1997

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity.

OBJECTIVE: To assess nucleosome plasma levels in patients with systemic lupus erythematosus (SLE) and to study the correlations with serum antinucleosome, anti-double-stranded DNA (anti-dsDNA), and antihistone antibody activities, as well as with disease activity (by the SLE Disease Activity Index [SLEDAI]). METHODS: In a cross-sectional study, we assessed 58 SLE patients for their plasma nucleosome levels. Plasma nucleosome levels as well as serum antinucleosome, anti-double-stranded DNA, and antihistone antibody activities were assessed by enzyme-linked immunosorbent assay. SLE activity was evaluated using the SLEDAI: RESULTS: The mean (+/-SD) plasma nucleosome concentration in SLE patients was 52 +/- 159 ng/ml (range 5-1,180), and was significantly higher than that of the controls (16 +/- 8.8 ng/ml, range 8-52; P = 0.03). Thirteen of the 58 lupus patients had levels over the range of normal (defined as the control mean + 3 SD, or 42 ng/ml). An inverse correlation was found between nucleosome plasma levels and serum antinucleosome antibody activity in the entire group of SLE patients, those with active disease, and those with inactive disease, respectively. No correlation was found between the SLEDAI and nucleosome plasma concentrations. CONCLUSION: Nucleosome plasma levels may be normal or increased in SLE, and found in patients with active or inactive SLE. Longitudinal studies are needed to further establish whether high levels of circulating nucleosomes may predict the occurrence of an SLE flare.

Adolescent↗
PubMed1997

Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment.

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a rare condition characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse swelling, weight gain, and renal shut-down. From the first publication in 1960, only 34 cases have been reported. OBJECTIVE: To collate enough patients to observe the natural history of the disease and evaluate the efficacy of empiric treatments. DESIGN: Multicentric retrospective study. RESULTS: Thirteen patients (6 women and 7 men) were collated with a mean follow-up of 6.4 years. Eight patients are still alive after a mean of 5.6 years (range 1 to 15). Three patients out of the 11 who were not lost to follow-up died; 1 during an attack and 2 because of a progression towards multiple myeloma. CONCLUSIONS: Our series shows an improvement in the prognosis of SCLS due most likely to improved management during attacks. Some patients' disease could evolve into a multiple myeloma. Treatment is still empiric and no prophylactic therapy, including terbutaline associated with aminophylline, has clearly proven its efficacy.

Acute Disease↗
PubMed1997

Anticardiolipin, anti-beta2-glycoprotein I, and antinucleosome antibodies in hepatitis C virus infection and mixed cryoglobulinemia. Multivirc Group.

OBJECTIVE: To investigate anticardiolipin antibodies (aCL), anti-beta2-glycoprotein I (anti-beta2GPI), and antinucleosome antibodies in patients with hepatitis C virus (HCV) with or without mixed cryoglobulinemia. aCL can appear in infectious diseases, but are not then associated with thrombotic events. Antibodies directed to beta2GPI, a co-factor of aCL, have been said to be associated with the presence of "autoimmune" aCL. About 50% of cases of essential mixed cryoglobulinemia are associated with HCV infection. High prevalence of autoantibodies directed to nuclear antigens has been found in HCV infection but the prevalence of antibody to nucleosome has not yet been reported. METHODS: Group 1: 29 patients with chronic HCV infection and mixed cryoglobulinemia. Group 2: 17 patients with chronic HCV infection but without mixed cryoglobulinemia. To analyze the possible effect of mixed cryoglobulinemia itself on aCL production, we also studied 22 patients with essential mixed cryoglobulinemia and no HCV infection (Group 3). In addition, 96 healthy blood donors were used as a control group (Group 4). Mixed cryoglobulinemia was detected by immunofixation. Anti-HCV antibodies were detected by 3rd generation tests, aCL, anti-beta2GPI, and antinucleosorne antibodies were detected by ELISA. In patients with mixed cryoglobulinemia, we also looked for aCL separately in cryoprecipitate and in serum after extraction of mixed cryoglobulins to investigate a possible "capture" of aCL in the cryoprecipitate. RESULTS: IgG aCL were more frequently found in patients with HCV than in controls [9/46 (20%) vs 2/96 (2%); p < 0.001]. The prevalence of aCL was similar in patients with HCV with or without mixed cryoglobulinemia (6/29 vs 3/17; p = NS). No patient with positive aCL had anti-beta2GPI, antinucleosome antibodies, thrombotic events, or thrombocytopenia. IgG aCL were more frequent in patients with mixed cryoglobulinemia, whatever their status for HCV infection, than in subjects without mixed cryoglobulinemia [8/51 (16%) vs 5/113 (4%); p < 0.02]. The prevalence of aCL was similar in patients with type II or type III mixed cryoglobulinemia. When we looked for aCL separately in serum and in cryoprecipitate, we did not find aCL in cryoprecipitate. In patients with HCV, the prevalence of aCL was not different whether patients were treated or not with interferon alpha. CONCLUSION: IgG aCL are frequently found in patients with HCV regardless of status for mixed cryoglobulinemia. These aCL have the characteristics of infection related aCL: low titer, absence of thrombotic events, and absence of anti-beta2GPI. The high proportion of aCL in patients with mixed cryoglobulinemia compared to those without, and the absence of antinucleosome antibodies, suggest that these aCL may be secondary to endothelial damage induced by mixed cryoglobulinemia or HCV itself, rather than to nonspecific polyclonal lymphocyte activation.

Antibodies, Anticardiolipin↗
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↗
PubMed1996

[Antiphospholipid antibody/cofactors. What are they? Why, when and how to search for them? Is treatment justified?].

Antiphospholipid antibodies are a wide family of antibodies, dominated by lupus anticoagulant (LA) and anti-cardiolipin antibodies (aCL), encountered in various circumstances. Unnecessary laboratory tests can be avoided by carefully weighing the indications, especially regarding patient age. Three steps are required to demonstrate LA: screening, mixing studies, then confirmation by neutralization tests. Two coagulation tests at least should be performed aCL are detected with ELISA kits using plates coated with cardiolipin. Due to the large number of kits available and to the lack of agreement on cut-off values, all laboratories must indicate their own standards. Other kits use plates coated with a mixture of phospholipids. Recent data suggest that pathogenic aPL are more specifically directed against phospholipid-associated proteins rather than towards phospholipids. In the future, tests for aCL might be replaced by tests for beta 2-glycoprotein I. The presence of aPL requires a specific treatment only in patients presenting clinical manifestations thought to be aPL-induced (thromboses, fetal losses). Long term warfarin aimed at an INR of 3-3.5 is effective for the secondary prevention of thrombosis. In primary APS, prevention of recurrent miscarriages is frequently achieved by a combination of subcutaneous heparin plus aspirin.

Antibodies, Antiphospholipid↗
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↗