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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 469 records · Page 26Linked to original sources
PubMed1995

Role of beta 2-glycoprotein I in the antiphospholipid antibody binding to endothelial cells.

A group of anticardiolipin antibodies (aCL) require beta 2-glycoprotein I (beta 2GPI) to recognize their target, which might be located on endothelial cells (EC) and/or platelets. Following incubation with epithelial cells, 13 of 30 lupus sera retained EC-reactive antibodies of the IgG, IgA and IgM isotypes. Associated aCL and anti-phosphatidylethanolamine antibodies were partly absorbed on eC as well as EC. The former antibodies were more efficiently removed in the presence than in the absence of the latter. The presence of beta 2GPI in the affinity-purified aCL preparations may explain their binding to EC, as this cross-reaction was abrogated by the removal of the cofactor and restored by its re-introduction. Seventy four per cent of EC were faintly stained with polyclonal or monoclonal antibody directed to the cofactor. The beta 2GPI mediated aCL binding to EC membranes could this be influential in the development of thrombosis and/or thrombocytopenia in aCL-positive patients.

Adolescent↗
PubMed1995

Antiphospholipid syndrome and the idiotypic network.

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 +/- 5.0 s vs. 22.4 +/- 1.7 s, in the non-immunized mice). Mice immunized with TM1B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The presence of antiphospholipid antibodies in acute myocardial infarction.

This study was undertaken to determine if there is an association between increased titers of five different antiphospholipid antibodies (aPLA) in young patients' sera and the occurrence of acute myocardial infarction (AMI). Antibodies to anticardiolipin (aCL), anti-phosphatidylserine (aPS), antiphosphatidylinositol (aPI), anti-phosphatidylcholine (aPC), and anti-phosphatidylethanol amine (aPEA) were measured in 214 patients (102 patients, 102 healthy controls and 10 patients with antiphospholipid syndrome). These antibodies were measured twice (within 4h of onset of acute myocardial ischemic chest pain and 3 months after the myocardial infarction) by enzyme linked immunosorbent assay (ELISA). Elevated titers of four different aPLA were detected in 6.9% of all patients with AMI on hospitalization. Titers of aPLA in AMI were elevated in the younger age group < 50 years old (P < 0.001) and in men only (not statistically significant). No correlation was found between the presence of aPLA and cardiovascular risk factors (smoking, hypertension, diabetes mellitus and hyper-cholesterolemia). Three of the seven patients with increased titers of aPLA did not have any other cardiovascular risk factors. The titers of aPLA were within normal range 3 months after AMI. Evidence of significantly elevated titers of different aPLA at the early stage of AMI suggests that these autoantibodies are present before the AMI and are not secondary to them. The disappearance of the elevated aPLA 3 months after AMI may be due to an absorption effect or possibly a cyclic phenomenon similarly found in other autoimmune diseases. aPLA may be an additional risk factor for AMI, and should especially be considered in a patient of the younger age group without apparent cardiovascular risk factors.

Adult↗
PubMed1995

Abrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin.

OBJECTIVE: To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. RESULTS: Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDAN and aCL antibodies in the IVGG preparation. CONCLUSION: Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

Animals↗
PubMed1995

The occurrence of thromboembolic events following airplane flights--'the economy class syndrome'.

The occurrence of thromboembolic phenomena following long-distant airplane flights is well characterized in the literature. However, it seems that despite being repeatedly described, the recognition of its implications by the medical services at the airports is still insufficient. We describe two cases: the first presented with a clinical picture consistent with the diagnosis of pulmonary embolus validated by a lung perfusion-ventilation scan, and the second, with deep vein thrombosis in his left femoral vein. Both patients were diagnosed several days after a prolonged airway flight. The purpose of this article is to draw attention to the thromboembolic phenomena known to be associated with airplane flights, provide possible mechanisms to account for their envolvement, and emphasize the measures that should be taken to prevent their occurrence.

Aged↗
PubMed1995

Aspirin modulates interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome.

OBJECTIVE: The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. METHODS: Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. RESULTS: When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 micrograms/ml), a marked stimulation of IL-3 production was noted. When NDGA was added to mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher dose of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261%, respectively, in the stimulation of IL-3 production (p < 0/01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. CONCLUSION: Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.

Animals↗
PubMed1995

Carbohydrate-deficient transferrin and false-positive results for alcohol abuse in primary biliary cirrhosis: differential diagnosis by detection of mitochondrial autoantibodies.

Primary biliary cirrhosis (PBC) is one of the few nonalcohol-induced liver pathologies that causes false positives in assays of carbohydrate-deficient transferrin (CDT) for diagnosing alcohol abuse. CDT was quantified by isoelectric focusing-immunoblotting-laser densitometry (IEF-IB-LD) analysis of serum from 117 women: 57 PBC patients, 20 alcohol abusers, and 40 healthy donors. Only 5% (3 of 57) of PBC patients were positive at the densitometric cutoff value chosen (> 90% specificity). Serum samples from 15 PBC patients were further evaluated by IEF-IB-LD and CDTect chromatography-RIA. Receiver-operating characteristic (ROC) analysis showed that IEF-IB-LD better discriminated between PBC and alcohol abuse than CDTect did. By ROC analysis, mitochondrial autoantibodies to pyruvate dehydrogenase antigen M2 detected by enzyme immunoassay yielded optimal test performance for diagnosing PBC. Of six patients falsely positive for CDT by CDTect, five (83%) tested M2-positive. Thus, abnormal CDT results should be further evaluated by mitochondrial antibody testing in patients with findings compatible with PBC.

Alcoholism↗
PubMed1995

Laboratory diagnosis of antiphospholipid syndromes.

The search for clinical outcomes associated with antiphospholipid antibodies (aPL) has been ongoing for a decade. This article focuses on the clinical use of tests for the detection of aPL. A review of the current thinking regarding the pathophysiology of antiphospholipid syndromes is relevant to the discussion of different aPL assays and methodologies. The value of aPL testing in specified patient populations is analyzed.

Antiphospholipid Syndrome↗