[A non-automatic diagnosis].
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Biomedical subjects
Publications and source records attributed to Z Amoura.
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A 50-kDa protein was purified as a potential receptor, using an affinity matrix containing biotinylated F14.6 or H9.3 anti-DNA mAbs derived from autoimmune (New Zealand Black x New Zealand White)F(1) mouse and membrane extracts from cells. This protein was identified as calreticulin (CRT) by microsequencing. Confocal microscopy and FACS analysis showed that CRT was present on the surface of various cells. CRT protein was recognized by a panel of anti-DNA mAbs in ELISA. The binding of F14.6 to lymphocytes and Chinese hamster ovary cells was inhibited by soluble CRT or SPA-600. Thus, the anti-DNA mAbs used in this study bound to CRT, suggesting that CRT may mediate their penetration into the cells and play an important role in lupus pathogenesis.
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CONTEXT: Discordant data have been reported about the prevalence of hepatitis C virus (HCV) infection in patients with lymphoproliferative diseases and the putative role of HCV in lymphomagenesis. OBJECTIVE: To assess the prevalence of HCV infection in patients admitted to a hematology department in Paris, France. DESIGN: Prospective, controlled study. SETTING: University medical center. PATIENTS: 813 patients admitted to the Hematology department (164 B-cell non-Hodgkin's lymphoma, 34 Hodgkin's diseases, 107 chronic lymphocytic leukemia, 54 multiple myeloma, 12 Waldenström's macroglobulinemia, 17 acute lymphoblastic leukemia, 6 hairy cell leukemia, 189 myeloproliferative diseases, 6 solid organ tumors, and 224 nonmalignant diseases) and 694 patients admitted to the Internal Medicine department (control group). MEASUREMENTS: All patients were tested for antibodies to HCV by a third-generation enzyme-linked immunosorbent assay. RESULTS: HCV antibodies were detected in 20 of 813 (2.46%) patients in Hematology including 11 of 394 (2.79%) patients with lymphoproliferative diseases, 3 of 164 (1.83%) B-cell non-Hodgkin's lymphoma, 2 of 107 (1.87%) chronic lymphocytic leukemia, 1 of 54 (1.85%) multiple myeloma, 1 of 189 (0.5%) myeloproliferative diseases, and 8 of 224 (3.57%) nonmalignant hematologic diseases. HCV antibodies were detected in 3 of 694 (0.43%) patients in the control group. HCV contamination preceded B-cell non-Hodgkin's lymphoma only in 2 of 3 HCV-positive patients. CONCLUSION: The prevalence of HCV infection was low (1.83%) in patients with B-cell non-Hodgkin lymphoma. HCV seems not to play a major role in the pathogenesis of B-cell lymphoma in France. Cofactors should be stressed to explain geographical discrepancies.
A case of epithelioid sarcoma involving the soft tissues of the ankle is presented. The tumor was a hemorrhagic, fluid-filled, multiloculated lesion with inflammatory changes in the surrounding planes. Tuberculous abscess was diagnosed on the basis of the clinical picture, ultrasound and MRI findings. Surgical exploration of the ankle mass was carried out because of lack of local healing while the patient's general and pulmonary status improved on antituberculosis treatment. This was an unusual case of epithelioid sarcoma mimicking a multilocular abscess.
OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.
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A 48 year old woman was referred to hospital for buccal discomfort. Physical examination showed a macroglossia and features of xerostomia. She was diagnosed as having primary Sjögren's syndrome according to the criteria proposed by the European Community study group in 1993. Furthermore, a lower lip salivary gland biopsy showed amyloid deposits that were also seen in the stomach and in the bone marrow. Echocardiography was consistent with cardiac amyloidosis. Serum immunofixation identified a monoclonal IgGlambda. As far as is known, this is the first report of systemic primary amyloidosis associated with Sjögren's syndrome. The relation between these two disorders is discussed.
BACKGROUND: Oral anticoagulants and pulse high-dose intravenous methylprednisolone are often administered concomitantly, but no data on potential interactions are available. OBJECTIVE: To assess possible potentiation of oral anticoagulation by high-dose intravenous methylprednisolone. DESIGN: Prospective cohort study. SETTING: University hospital in Paris, France. PATIENTS: 10 consecutive patients concomitantly receiving methylprednisolone and oral anticoagulants (fluindione and acenocoumarol) and 5 consecutive controls receiving methylprednisolone alone. MEASUREMENTS: Serial determinations of the international normalized ratio (INR) and clotting factors during administration of pulse methylprednisolone. The total plasma fluindione concentration was determined in 3 patients. RESULTS: The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration. Plasma fluindione concentrations and the INR increased after methylprednisolone administration. Methylprednisolone alone did not increase prothrombin time. CONCLUSIONS: The action of oral anticoagulants is potentiated by intravenous high-dose methylprednisolone. The INR should be monitored daily during concomitant administration of these medications.
OBJECTIVE: To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to determine factors, such as antibody subclass, that may influence the pathogenicity of these antibodies in relation to disease activity. METHODS: IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma (systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), and 319 had other CTD, including Sjögren's syndrome, inflammatory myopathy, rheumatoid arthritis, primary antiphospholipid syndrome, Wegener's granulomatosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Behçet's syndrome, and sarcoidosis. Antinucleosome-positive sera were further analyzed, by isotype-specific ELISA, for antinucleosome and anti-double-stranded DNA (anti-dsDNA) IgG subclasses. RESULTS: SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinucleosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive SLE, and their levels showed a positive correlation with SLE disease activity. Of note, an increase in levels of antinucleosome of the IgG3 isotype was observed during SLE flares, and this increase was found to be closely associated with active nephritis. Levels of antinucleosome of the IgG1 subclass showed a trend toward an inverse correlation with SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed in relation to SLE severity or clinical signs. CONCLUSION: Our data suggest that IgG antinucleosome is a new marker that may help in the differential diagnosis of CTD; antinucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in particular, of lupus nephritis.
OBJECTIVE: To describe new assays for the detection and quantification of antibodies to RNPs in rheumatic diseases, using soluble nuclear antigens synthesized de novo in reticulocyte lysates. METHODS: Sera from 381 patients with various rheumatic diseases, including 212 patients with systemic lupus erythematosus (SLE), were analyzed in order to evaluate the sensitivity and specificity of serum autoantibody reactivities to several recombinant soluble autoantigens: U1-A RNP, Sm-B, SSA/Ro 52 and SSA/Ro 60, SSB/La, and Ku. Radioligand assays (RLAs) were performed following the in vitro transcription and translation of each autoantigen from the corresponding complementary DNA, labeled with 35S-methionine. The radiolabeled protein was then bound by the specific serum autoantibody, forming immune complexes that were captured by protein A-Sepharose beads and quantified by counting the radioactivity. RESULTS: Among the SLE patients, 44% were positive for anti-U1-A RNP activity, 34% for anti-Sm-B, 44% for anti-SSA (32% for Ro 52 and 46% for Ro 60), 32% for anti-SSB/La, and 11% for anti-Ku reactivities. SSA antibodies had a high frequency in patients with mixed connective tissue disease (MCTD) (80%); 65% of these patient sera reacted with Ro 52, 45% with Ro 60, and 45% with U1-A RNP. Twenty percent of the MCTD patients also exhibited antibodies to Sm-B and Ku. In patients with Sjögren's syndrome, anti-SSA was the main anti-RNP antibody (63%), together with SSB/La antibodies (44%). Among patients with inflammatory myopathy, only antibodies against Ro 52 (36%) and Ro 60 (36%) were present. These new RLA allowed observation of a strong correlation (P < 0.0001) between Sm-B antibody levels and the severity of SLE (as measured by the SLE Disease Activity Index), and establishment of a correlation between anti-U1-A RNP antibodies and the occurrence of SLE nephritis (P < 0.02). All RLAs were highly specific for the antigen tested and displayed, in the disease groups studied, a higher sensitivity than conventional immunodiffusion assays. CONCLUSION: These highly sensitive, specific, and quantitative RLAs represent new tools for the detection of autoantibodies to RNP antigens in rheumatic diseases, and may be useful for (differential) diagnosis in clinical practice.
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INTRODUCTION: Steroid therapy remains the standard treatment for giant cell arteritis but is sometimes incriminated in the occurrence of ischemic events, particularly in the early phase of the disease. EXEGESIS: We report four cases of ischemic events observed early after initiation of steroid therapy in giant cell arteritis. We also reviewed the literature. CONCLUSION: Though the close temporal relationship between the initiation of steroids and the occurrence of ischemic events suggests a causative link, other factors such as arteritis itself or arteriosclerosis would also play a role. Systematic prescription of an anticoagulant should be discussed at the initial phase of treatment of giant cell arteritis.
OBJECTIVES: To evaluate the capacity of B-Mode ultrasonography (B-Mode US) and electron-beam computed tomography (EBCT) to detect arterial changes in Takayasu's arteritis. METHODS: EBCT angiography of the thoracoabdominal aorta and pulmonary artery, and B-mode US of large superficial arteries (common carotid, subclavian, and common femoral arteries) were performed prospectively in 43 consecutive patients with established Takayasu's arteritis. The arterial wall thickness was measured, and lumen changes (stenosis, aneurysm) were noted. RESULTS: The combined results of B-Mode US and EBCT examinations showed that every patient had at least one abnormality at the studied sites. The median score of abnormal sites was 7. The most frequent lesion was a characteristic long, homogeneous, circumferential thickening, visualized in 52% of examined sites and in all patients but one (98%). Stenosis was detected by US and by EBCT, respectively, in 44% and 32% of patients, and aneurysm in 0.4% and 68%. CONCLUSIONS: In Takayasu's arteritis, B-Mode US and EBCT was able to visualize the classical caliber abnormalities (stenosis, aneurysm) and, in contrast to angiography, to depict vessel wall thickening, a major pathologic feature of the disease. Both these safe techniques seem more useful than angiography to characterize and map the vascular lesions of Takayasu's arteritis.
PURPOSE: To evaluate the efficacy of interferon alfa-2a (IFN alfa) in severe uveitis associated with Behçet's disease, that is refractory to steroids and conventional immunosuppressive agents. PATIENTS AND METHODS: Patients with Behçet's disease (according to the International Study Group criteria), who relapsed despite steroids and immunosuppressive agents, were included in this retrospective study. Ophthalmological examination, laser flare photometry, and fluorescein angiography associated with laboratory tests were performed at regular intervals. IFN alfa (3 millions units thrice a week) was injected subcutaneously. RESULTS: Eight patients (sex ratio: 1) were included between May 1995 and January 1999. The mean age was 29.1 years (14-54 years) and the disease was present between 11 and 167 months before the administration of IFN alfa. IFN alfa was efficient in all cases with a mean follow-up of 22 months (10-55 months). Steroids were tapered from a mean dosage of 47 mg/d to a mean dosage of 8.5 mg/d. Ocular inflammation was controlled and visual acuity improved in all cases. Treatment was generally well tolerated despite a constant but transient flu-like syndrome. IFN alfa was tapered in three patients and stopped in one case without any relapse after five months. CONCLUSIONS: Within the limitations of this retrospective study, low-dose IFN alfa seems to be well tolerated, promising in the management of refractory forms of uveitis due to Behçet's disease, and effective in allowing a reduction of steroid dosage. A prospective controlled study is necessary to confirm these preliminary results.
Nucleosomes play a central role in the antinuclear antibody response in lupus. Lupus anti-dsDNA and antihistone antibodies directed toward nucleosomes belong together with nucleosome-specific antibodies, to a broad antinucleosome antibody family. Besides anti-dsDNA, nucleosome-specific antibodies have a major role in the pathophysiology of systemic lupus erythematosus (SLE) and emphasize the role of nucleosome-antinucleosome immune complexes. Antinucleosome immunoglobulin G antibodies are a more sensitive marker of SLE than anti-dsDNA, and are almost exclusively found in lupus, scleroderma, and mixed connective tissue diseases. An understanding of the key role of the nucleosome will likely make possible new therapeutic interventions in SLE, such as a tolerance induction to the subnucleosomal particles.