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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 307 records · Page 17Linked to original sources
PubMed1998

Increased prevalence of autoantibodies in celiac disease.

Several features suggest an immune mechanism operates in celiac disease. Information on the autoantibody repertoire in this condition is lacking. The purpose of the study was to investigate the reactivity of celiac patients sera to various autoantigens widely distributed in the human intestine. Seventy children, celiacs and controls, were evaluated for serum autoantibodies using ELISA and immunofluorescence. Celiac patients had increased prevalence of serum anti-single-stranded DNA (14%), anti-double-stranded DNA (23%), anti-cardiolipin (14%), and anti-endomysial autoantibodies (63%). The relevance of this finding on the extraintestinal manifestations of celiac disease or the coexistence of autoimmune conditions and celiac disease remains to be determined.

Autoantibodies↗
PubMed1998

High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response.

Heparin-induced thrombocytopenia (HIT) is a common drug induced autoimmune condition. The thrombocytopenia is caused in most cases by an antibody directed against the complex PF4/heparin. Recently, we have induced an experimental model of HIT by idiotypic manipulation. To confirm further the idiotypic involvement of HIT, we have treated successfully three patients with HIT with high-dose intravenous gamma-globulin (IVIG). Our three patients joint other two cases previously reported who were treated with IVIG and point to the efficacy of this type of therapy with minimal side effects. IVIG suppression of the anti-PF4/heparin autoantibody may support the idiotypic etiology of HIT.

Aged↗
PubMed1998

Anti-DNA and antiphospholipid antibodies in IVIG preparations: in vivo study in naive mice.

Intravenous immunoglobulins (IVIG) are therapeutic preparations of pooled normal polyspecific immunoglobulin G. We investigated the presence and the in vivo pathogenic potential of autoantibodies against phospholipids and DNA in several commercial IVIG preparations. The presence of autoantibodies and their antiidiotypic antibodies in the IVIG preparations was detected by ELISA. Naive mice were actively immunized with either IVIG preparations or pathogenic monoclonal antibodies (mAbs) against cardiolipin (CL) or DNA, in an attempt to induce autoimmune conditions. The mice were tested for the presence of mouse autoantibodies (auto-Abs) and for clinical parameters of autoimmune diseases. We found high levels of auto-Abs against a panel of phospholipids and DNA, as well as their antiidiotypic Abs, in all the IVIGs. Affinity studies pointed to a lower affinity of auto-Abs of IVIG origin to their respective antigens compared to pathogenic mAbs. Mice immunized with pathogenic anti-CL mAb had high levels of antiphospholipid auto-Abs, accompanied by thrombocytopenia, prolonged aPTT, and an increased fetal resorption rate. Mice immunized with pathogenic anti-DNA mAb had elevated anti-DNA and anti-CL auto-Abs, along with a high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. Following immunization with IgGs from IVIG batches, mice developed high levels of auto-Abs against phospholipids and DNA, similar to mice immunized with pathogenic anti-DNA or anti-CL mAbs, but none of the mice expressed the clinical manifestations compatible with the presence of these autoantibodies. We conclude that commercial IVIG preparations contain high levels of antiphospholipid and anti-DNA auto-Abs, as well as their antiidiotypic Abs. Although these Abs induced the generation of mouse auto-Abs upon active immunization, following idiotypic manipulation they did not prove to be pathogenic in vivo.

Animals↗
PubMed1998

Autoimmune diseases and autoimmunity post-bone marrow transplantation.

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.

Autoimmune Diseases↗
PubMed1998

Interleukin-3 and pregnancy loss in antiphospholipid syndrome.

Cytokines play an important role in the progression of autoimmune diseases, and therefore it is not surprising that their levels may be altered in some of these diseases. Interleukin-3 (IL-3), which is an hematopoietic growth factor as well as an important factor that aids in embryo implantation and placental development, was found to be decreased both in pregnant women with antiphospholipid syndrome (APS) compared with a control group, and in animal models of APS. Treatment of animals having APS with IL-3 succeeded in prevention of disease manifestations. In this communication we review IL-3 and APS interrelationship, and discuss the role of aspirin and other commonly used drugs, with respect to IL-3 levels in APS.

Abortion, Spontaneous↗
PubMed1998

Anti-phospholipid autoantibodies--do they have a pathogenic role in infertility?

Anti-phospholipid syndrome includes a variety of clinical manifestations, among which is recurrent pregnancy loss. Recently, it was suggested that anti-phospholipid antibodies might also have a role in infertility, mainly in unexplained infertility. Most of the studies report about an increased prevalence of these antibodies in infertile women; however, data regarding the implication of these antibodies on treatment outcome (mainly in in-vitro fertilization) and if there is a beneficial effect of treating these patients with aspirin, heparin and prednisone--remains still controversial. In this communication we review the literature reports of association of anti-phospholipid antibodies and infertility, and deal with the question whether they have a pathogenic role in these cases.

Antibodies, Antiphospholipid↗
PubMed1998

Immunomodulation of experimental antiphospholipid syndrome.

The various therapeutic modalities which are found to be beneficial in experimental antiphospholipid syndrome include: bone marrow transplantation, anti-CD4 monoclonal antibodies, bromocriptine, intravenous immunoglobulins and anti-idiotypes, interleukin-3, and various anti-coagulant and anti-aggregate agents. The advantage of animal models is the ability to evaluate experimental treatments that cannot be tested directly on patients. In this paper, we review the effect of these agents on animal models of antiphospholipid syndrome, their mechanisms of action, and their clinical implications.

Animals↗
PubMed1998

Hantavirus seropositivity in Israeli patients with renal failure.

The hantavirus is known to cause hemorraghic fever with renal syndrome (HFRS), which is widely spread in Europe and Asia. Several reports have shown an association of hantavirus antibody titers and the occurrence of renal dysfunction. From these observations, it appears that the virus is widely distributed, and different strains prevail in various areas. In the present work we studied 81 patients with end-stage renal-failure under hemodialysis (HD) treatment, 55 with mild to moderate renal failure, and 50 healthy subjects for the presence of antibodies to Hantaan and Puumala viruses. We found that 12.3% of the hemodialysis patients and 9% of the mild to moderate renal failure patients had elevated IgG anti-body titers to Puumala virus compared with 2% of the controls. IgM antibodies to Puumala virus was principally elevated in patient with chronic renal failure (CRF) not on hemodialysis (14.5%) compared with the hemodialyzed (1.2%) and controls (0%) subjects. Hantaan virus IgG antibodies were detected in 3.7% of the HD patients, 5.5% of the CRF not on HD, and in none of the controls. IgM Hantaan antibodies were found only in the non-HD renal failure patients. None of the sera were found to contain antibodies to phospholipids or single-stranded DNA. These results emphasize the widespread nature of infection with hantaviruses and imply that elaborate testing for these serologies should be performed, especially in patients with unexplained renal failure.

Female↗
PubMed1998

Characterization of murine monoclonal anti-endothelial cell antibodies (AECA) produced by idiotypic manipulation with human AECA.

The IgG fraction of human anti-endothelial cell antibodies (AECA) obtained from a patient with Wegener's granulomatosis was used as immunogen to raise AECA mAb in mice selected among those which developed vasculitis-like lesions after immunization. Three mAb (BGM, 3C8 and 7G2), selected by cyto-ELISA and flow cytometry analyses, featured a specific reactivity with human umbilical vein endothelial cells (HUVEC) and the mouse endothelial cell line H5V; on the contrary, HEp2 cells, the murine melanoma B16 cell line, the extracellular matrix as well as several other antigens tested were not recognized. BGM mAb, an IgG3 precipitating a 70 kDa structure from HUVEC, was able to induce endothelial cells to secrete amounts of IL-6 significantly higher than irrelevant controls or mAb binding different endothelial antigens (i.e. CD31, CD29, ICAM-1 and HLA class I). BGM mAb induced significant levels of antibody-dependent cell cytotoxicity (13 +/- 2.5 versus 0.6 +/- 0.03%). To the best of our knowledge, BGM is the first murine mAb specific for human endothelial cells generated by idiotypic manipulation; secondly, its biological properties further support the notion of a pathogenic role for AECA in autoimmune-mediated diseases.

Animals↗
PubMed1998

Massive proteinuria as a main manifestation of primary antiphospholipid syndrome.

Renal involvement in antiphospholipid syndrome (APS) is increasingly reported. So far, massive proteinuria as the principal feature of primary APS (PAPS) has not been well documented. We describe 3 patients with PAPS and massive proteinuria. Renal biopsy was performed in all 3, and features consistent with membranous and focal segmental glomerulopathy were disclosed. These histological lesions were not yet reported in PAPS. We conclude that the spectrum of renal lesions in PAPS is diverse and that it should be considered in the differential diagnosis of patients with massive proteinuria.

Adult↗
PubMed1998

Autoantibody level modification in adult patients with idiopathic thrombocytopenic purpura following intravenous immunoglobulin treatment.

The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18-72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (> 10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.

Adolescent↗
PubMed1998

Atherosclerosis and the antiphospholipid syndrome: a link unravelled?

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to beta2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.

Animals↗
PubMed1998

Lessons from experimental APS models.

Several animal models for antiphospholipid syndrome (APS) have been reported in the literature. These experimental models have contributed significantly in resolving enigmas in this multisystemic disease. We, and others have previously shown the pathogenicity of anticardiolipin (aCL) antibodies in pregnancy outcome. We have expanded our studies to show the pathogenicity of aCL antibodies in renal dysfunction and neurological and behavioral impairments in animals with experimental APS. Animals immunized with aCL or with the cofactor beta2GPI developed clinical manifestations of APS, including fetal loss, thrombocytopenia and neurological and behavioral dysfunction, along with elevated levels of aPL antibodies. In another animal model, peripheral blood lymphocytes (PBLs) derived from APS patients could initiate APS manifestations with renal dysfunction in SCID mice. A unique in vivo model for thrombus formation was recently established to show the pathogenicity of aPL in thrombosis associated with APS. Histological evaluation of affected tissues derived from animals or from patients with APS have pointed to common mechanisms underlying APS, showing mainly thrombotic changes accompanied by mild inflammatory reaction.

Abortion, Habitual↗
PubMed1998

Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus.

OBJECTIVE: To examine the effect of diets with different polyunsaturated fatty acid contents, including linseed oil which contains 70% omega-3 fatty acids, on autoantibody production in idiotype induced mouse model of systemic lupus erythematosus (SLE). METHODS: Five different fats were fed to mice with induced SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and histological examination of kidneys were carried out. RESULTS: SLE mice fed linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less severe kidney damage than mice fed other diets, including fish oil. CONCLUSION: Use of linseed oil may attenuate the severity of SLE and this diet may be recommended for other auto-immune diseases as well.

Animals↗
PubMed1998

Anti-endothelial cell antibodies in the sera of hyperprolactinemic women.

Prolactin (PRL) is closely associated with autoimmune diseases in animal models and humans, and several disease-related autoantibodies were reported in increased titers in patients with hyperprolactinemia (HPRL). We studied the presence of anti-endothelial cell antibodies (AECA) and other autoantibodies in sera of female patients with HPRL. Sera from 25 HPRL patients and 10 healthy female controls were tested for AECA (against both macrovascular and microvascular endothelial cell antigens), anti-dsDNA, and anti-cardiolipin (anti-CL) using ELISA. Sera were considered positive for the autoantibody when the optical density (OD) value was more than 3 s.d. above the mean of the OD in normal controls. Sera from 13 patients were obtained repeatedly during dopaminergic anti-PRL treatment, to relate PRL level or anti-PRL treatment with the autoantibody levels. Elevated micro and/or macrovascular AECA were observed in sera from 19/25 patients (76%). Elevated titers of anti-CL Abs, all beta2-GPI-dependent, and low levels of anti-dsDNA antibodies (Abs) were also observed in the HPRL patients. Inhibition studies showed that the affinity purified AECAs bound the endothelial cell (EC) antigens in a dose-dependent manner. Titers of AECA as well as anti-DNA and anti-CL autoantibodies did not correlate with PRL level nor with the use or duration of anti-PRL treatment. None of the HPRL patients presented clinical manifestations of autoimmune disease. We conclude that elevated levels of AECA as well as anti-DNA and anti-CL autoantibodies are frequent in hyperprolactinemia. Our results further support the association of PRL and autoimmunity, and may point to a relationship between AECA-associated diseases and HRPL. The presence of autoantibodies in patients with HPRL might portend an increased risk for future development of autoimmune disease.

Antibodies, Anticardiolipin↗
PubMed1998

Immunomodulation of murine experimental SLE-like disease by interferon-gamma.

The objective of this study was to assess the impact of murine recombinant IFN-gamma and anti-IFN-gamma monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16/6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-gamma, anti-IFN-gamma mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-gamma, intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-gamma treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-gamma treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-gamma treated mice. IFN-gamma upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-gamma administration can aggravate the clinical and laboratory outcome of 16/6 id induced lupus in BALB/c mice.

Animals↗