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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 163 records · Page 9Linked to original sources
PubMed2001

Mechanisms of action of the anti-atherogenic effect of magnesium: lessons from a mouse model.

Magnesium (Mg) fortification of drinking water succeeded in inhibition of atherogenesis development in a transgenic model of atherosclerosis-prone mice fed a high-cholesterol content diet. In order to delineate possible mechanisms of action of the anti-atherogenic effect of Mg, the involvement of LDL oxidation was studied. We determined the susceptibility of LDL to Cu+2 oxidation, anti-oxidized LDL antibody levels, and liver content of retinol and retinyl-palmitate. In order to study another possible mechanism we tested platelets interaction with extracellular matrix in both male and female mice with or without Mg fortification of drinking water. No difference was found in susceptibility of LDL to undergo oxidation. Female mice that received Mg had decreased anti-oxidized LDL antibody levels compared with control female mice, while there was no significant difference among male groups. On the other hand, only in the male group with Mg was a higher content of retinol and retinyl-palmitate found in the livers. Platelets coverage area on extracellular matrix was similar between groups. These results suggest that Mg might affect LDL oxidation, and thus atherogenesis.

Animals↗
PubMed2001

Cytokine levels in various intravenous immunoglobulin (IVIg) preparations.

The mechanisms of action of intravenous immunoglobulin (IVIg) in autoimmune diseases include modulation of cytokine levels. We examined therefore whether direct infusion of abnormally high levels of 13 different cytokines or cytokine-inhibitors within 5 different IVIg preparations have any role in modulation of their levels. None of the measured cytokines in any of the IVIg preparations tested were above the normal levels, and regarding some no traces could be detected. Hence, modulation of cytokine levels following IVIg therapy involves other mechanisms such as interference with their secretion or cytokine-specific blocking antibodies, rather than direct infusion of cytokines.

Cytokines↗
PubMed2001

The mosaic of autoimmunity.

Autoimmunity is a normal event, while autoimmune diseases result from an aberration of this normal phenomenon. The etiology of this switch is considered multifactorial with the final common pathway being the loss of normal self-tolerance in a particular organ or group of organs. Genetic, environmental, hormonal and immunologic factors (along with probably other yet unrecognised factors) are considered important in the development of these disorders. The particular autoimmune disease which any patient develops is most likely a result of which combination of factors the patient has accumulated. We begin with a brief review of immunobiology in order to arrive at a suitable definition of autoimmunity. This is followed by a concise description of the current theories regarding the development of autoimmune disease and the factors known to be associated with these illnesses. Concluding remarks address the factors that normally prevent the progression of autoimmunity to autoimmune disease and the application of current knowledge to future therapeutic approaches.

Animals↗
PubMed2001

[The mosaic of pemphigus].

Pemphigus is an autoimmune blistering disease of skin and mucous membranes. The classic types of pemphigus are pemphigus vulgaris and pemphigus foliaceus. In this review we summarize recent advancement in the etiology and the pathogenesis of pemphigus. Desmogleins--transmembrane glycoproteins involved in intracellular adhesion--were recognized as targets of pemphigus antibodies. It was found that the distribution and the expression of desmogleins can explain the difference in the localization of lesions in pemphigus vulgaris and pemphigus foliaceus. Pemphigus develops in a two-step process. The first step leads to the presence of a low titer of autoantibody, the second step results in a significant increase in the antibody titer which causes the clinical stage of the disease. Selective presentation of self peptides can explain the Major Histocompatibility Complex (MHC)--linked susceptibility to autoimmune diseases including pemphigus and rheumatoid arthritis. Peptides selective for the disease-associated molecules can be identified and used to search for microbiologic factors that can take part in the pathogenesis of pemphigus.

Autoimmune Diseases↗
PubMed2001

[Morbidity and mortality in systemic lupus erythematosus].

Systemic lupus erythematosus is an autoimmune disease that can affect any organ system, mostly central and peripheral nervous system, lungs, heart, kidneys, skin, serous membranes, and components of blood. Lupus is more prevalent in females, has no etiology, and has a distinct association with several immune response genes. Understanding and treatment of lupus has progressed in the last decade, contributing to the improvement in survival and quality of life. Improvement in prognosis is associated with many factors including the socioeconomic state, advanced medicine, and access to medical sources. Three aspects of the disease are necessary to establish and describe the prognosis in SLE: disease activity, accumulated damage, and health status/quality of life.

Humans↗
PubMed2000

Coronary calcium and anti-cardiolipin antibody are elevated in patients with typical chest pain.

The aim of this study was to examine whether detection of coronary calcium and the autoimmune response associated with atherosclerosis, either solely or in combination, are different in patients with typical and atypical chest pain. Coronary calcium as detected by spiral computerized tomography and levels of antibodies against cardiolipin (CL), oxidized low-density lipoprotein (ox-LDL), and beta2-glycoprotein-I (beta2-GPI) were studied in patients with typical chest pain (n = 52), atypical chest pain (n = 19), or without chest pain (n = 21). Patients with typical chest pain had higher mean levels of coronary calcium (expressed as natural transformation of total coronary calcium score) compared with patients with atypical chest pain and controls (5.04 vs 3.21 and 2.75, respectively; p < 0.001). The levels of anti-CL were (mean +/- SD of optical density multiplied by 1,000): 262 +/- 140, 170 +/- 82, and 230 +/- 115 for patients with typical chest pain, atypical chest pain, and controls, respectively (p = 0.016). No significant difference was found between groups regarding anti-ox-LDL and anti-beta2-GPI autoantibody levels. In the typical chest pain group, there was a higher prevalence of high total coronary calcium scores (p = 0.03) and high anti-CL levels (p = 0.01) than in the atypical chest pain group. Eighteen of 52 patients with typical chest pain (35%) had both high calcium scores and high antibody levels, whereas none of the 19 patients (0%) who had atypical chest pain had high levels of both (p = 0.003). A combination of both coronary calcium and anti-CL was associated with higher area under the receiver operator characteristic curves than for each separately. High coronary calcium scores or high anti-CL levels are found more often in typical than in atypical chest pain patients, but a combination of high levels of both can better differentiate typical from atypical chest pain patients.

Aged↗
PubMed2000

Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice.

BACKGROUND: It has been proposed that autoimmune factors can influence the progression of atherosclerosis. We have previously shown that immunization of LDL receptor-deficient (LDL-RD mice) with beta(2)-glycoprotein I (beta2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of beta2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice. METHODS AND RESULTS: LDL-RD mice were immunized with human beta2GPI. An additional group of mice were immunized with beta2GPI and boosted with the same antigen 3 weeks later. Control mice with immunized with human serum albumin. Lymphocytes obtained from the draining lymph node cells or from splenocytes of beta2GPI- or human serum albumin-immunized mice were stimulated in vitro with beta2GPI or with the mitogen concavalin A, respectively. The cultured lymphocytes were transferred intraperitoneally to syngenic LDL-RD mice, and the mice were fed a high-fat "Western" diet for 5 weeks until death. Mice injected with lymphocytes from draining lymph nodes or spleens of beta2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell-depleted splenocytes from beta2GPI were unable to promote lesion formation in the mice. CONCLUSIONS: The present study provides the first direct evidence for a role of antigen (beta2GPI)-reactive T cells in the promotion of fatty streaks in mice.

Adoptive Transfer↗
PubMed2000

Pathogenic role of anti-endothelial cell antibodies in systemic vasculitis.

Antiendothelial cell antibodies (AECA), a heterogeneous group of antibodies quite distinct from the ANCA family, have been detected in variety of diseases which share a varying degree of vessel wall damage. This review is mainly focused on Wegener's granulomatosis, Takayasu's arteritis and Kawasaki syndrome, which provide the best examples to evaluate the pathogenic and prognostic value of AECA. There is increasing evidence to show that AECA might be pathogenic in inducing autoimmune vascular disease. It is relevant to note that the presence and titre of AECA has been correlated with disease activity in systemic vasculitis. Experimental in vitro and in vivo models support a potential pathogenic role for AECA in sustaining immune-mediated vessel inflammation. Rather than being cytotoxic to endothelial cells, AECA are able to up-regulate the expression of adhesion molecules (E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and to induce the secretion of cytokine and chemokine which, in turn, cause leukocyte recruitment and adhesion. A recent idiotypic animal model has provided further evidence that AECA can be pathogenic.

Autoantibodies↗
PubMed2000

Anti-endothelial cell antibodies in patients with coronary atherosclerosis.

Anti-endothelial cell antibodies (AECA) have been shown to possess endothelial cell activation properties and to harbor pathogenic potential in experimental animal models of autoimmune systemic disorders. Atherosclerosis is a form of an inflammatory condition in which the immune system has been shown to be involved. The aim of the present study was to assess the presence of AECA in patients with coronary atherosclerosis. A total of 134 patients admitted for chest pain of suspected anginal origin were evaluated for coronary artery atherosclerosis by angiography. Sera were drawn prior to the procedure for the determination of AECA employing cyto-ELISA. AECA positive sera were further evaluated for its ability to promote in vitro E-selectin expression by HUVEC using a cell-based ELISA. Patients with no coronary artery involvement had levels of AECA that did not differ from those obtained for patients with confirmed coronary atherosclerosis (one, two or three vessel disease). Furthermore, AECA positive sera from patients, with or without coronary atherosclerosis displayed similar capacity of inducing E-selectin expression by endothelial cells. AECA may not stand as an optimal mean of discriminating atherosclerotic from non-atherosclerotic patients. The ability of AECA to activate endothelial cells is also not unique to patients with atherosclerosis and is evident also in age-matched control subjects.

Aged↗
PubMed2000

Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis.

Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65). In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-induced models that exhibit an inflammatory phenotype. Fatty streak formation in IL-4-knockout (IL-4 KO) mice immunized with HSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice. However, when injected with control (HSP-free) adjuvant, no differences were evident in the lesion size between wild-type and the IL-4 KO mice. Next, we studied comparatively the extent of humoral and cellular immune responses to HSP65 in the IL-4 KO and wild-type mice, as those are thought to be influential in murine atherosclerosis. Anti-HSP65 antibody levels were reduced in the HSP65-immunized IL-4 KO mice as compared with their wild-type littermates, whereas no differences were evident between the groups with respect to the primary cellular immune response to HSP65. Other than the absence of IL-4 in the knockout mice, the pattern of secreting cytokines interferon-gamma and IL-10 in concanavalin A-primed splenocytes was similar between the groups. HSP65-primed inguinal lymphocytes from IL-4 KO mice immunized with HSP65 secreted higher levels of interferon-gamma (previously shown to be proatherogenic in vivo) as compared with their wild-type controls. 12-/15-Lipoxygenase expression, known to be regulated by IL-4 and to contribute to murine atherosclerosis, in the lesions was not influenced by the immunization protocol used or by IL-4 disruption. Thus, IL-4 may prove a principal cytokine in the progression of early "inflammatory" atherosclerotic lesions and may serve as a target for immunomodulation.

Animals↗
PubMed2000

Dichotomic effects of IFN-gamma on the development of systemic lupus erythematosus-like syndrome in MRL-lpr / lpr mice.

Systemic lupus erythematosus (SLE)-prone female MRL-lpr / lpr (MRL-lpr) mice were treated with mouse or rat IFN-gamma under different experimental conditions, both prophylactically in 6- to 8 week-old animals and therapeutically in 12- to 18-week-old SLE-affected mice. It was found that IFN-gamma heterogeneously modulated the course of the disease in MRL-lpr mice. When administered prophylactically, IFN-gamma favorably modulated the histological, serological and clinical signs of the disease. Relative to untreated or PBS-treated control animals, the MRL-lpr mice which received IFN gamma were virtually free of inflammatory infiltration of the kidneys and the lungs, had lower levels of azotemia with reduction of both circulating IgG1, IgG2a and IgG3 and anti-double strand (ds) and single strand (ss) DNA antibodies, milder skin vasculitis, significantly reduced enlargement of their lymph nodes and lower weight of the spleens. IFN-gamma also lowered the rate of mortality of MRL-lpr mice. In contrast to these findings, therapeutically administered IFN-gamma worsened the course of the disease in MRL-lpr mice, which exhibited increased proteinuria, higher levels of IgG2a and IgG3 and anti-ds and -ss DNA antibodies, more aggressive nephritis and died at an earlier age than PBS-treated control mice. The dichotomic effect of IFN-gamma on disease manifestation in MRL-lpr mice offers new insights into the complex role of this cytokine in the regulation of systemic autoimmunity such as SLE.

Animals↗