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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 127 records · Page 7Linked to original sources
PubMed2001

Further experience with intravenous immunoglobulin in women with recurrent miscarriage and a poor prognosis.

PROBLEM: Women with three or more unexplained miscarriages have a 60% chance of a subsequent live birth. Intravenous immunoglobulin (IVIG) has not been conclusively shown to improve this prognosis. This study assessed the effect of IVIG in patients expected to have a poor outcome if untreated, i.e. women with five or more abortions, who have aborted after paternal leukocyte immunization or who continue to abort despite expressing anti-paternal complement dependent antibody. METHODS: Seventy-six women received IVIG in a dose of 400 mg/kg body weight, in one day (total 30-45 g) in the follicular phase of a cycle in which pregnancy was planned. A booster dose was administered when pregnancy was diagnosed. Their results were compared to an untreated control group of 74 women. RESULTS: Thirty-five (49%) pregnancies in treated women have resulted in live births or passed their previous stages of abortion compared to 23 (31%) in control patients (P = 0.04). CONCLUSIONS: These figures indicate that IVIG may prevent further miscarriages in this poor prognosis population. These figures are especially significant considering the doubt concerning the efficacy of IVIG in patients with three miscarriages and therefore a relatively good prognosis.

Abortion, Habitual↗
PubMed2001

Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS).

Activation and proliferation of lymphocytes requires the active signal transducer Ras. Activation of lymphocytes, associated with autoimmunity, may therefore be modified by S-farnesylthiosalicylic acid (FTS), a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE) and the primary antiphospholipid syndrome (APS). The objective of the present study was to examine the effect of FTS on laboratory and clinical pathology in the MRL/lpr mouse. Female MRL/lpr (n = 50) and MRL/++ control (n = 35) mice were treated intraperitoneally with either FTS (5 mg/kg/day) or saline between 6 and 18 weeks of age. The mice were weighed, tested for proteinuria and lymphadenopathy, lymphocyte proliferation, antibodies, grip strength and behaviour in an open field. FTS treatment resulted in a 50% decrease in splenocyte proliferation to ConA, LPS and a disease specific antigen, beta(2)-glycoprotein-I, and in a significant decrease in serum antibody levels against cardiolipin and dsDNA. Proteinuria and grip strength were normalized and lymphadenopathy and postmortem lymph node and spleen weights were significantly reduced in FTS treated MRL/lpr mice. These findings indicate that modulation of Ras activation has a significant impact on the MRL/lpr model and may represent a new therapeutic approach for the treatment of systemic autoimmune diseases such as SLE and APS.

Animals↗
PubMed2001

Induction and treatment of the antiphospholipid syndrome--lessons from animal models.

The diagnosis of antiphospholipid syndrome (APS) is based on a combination of clinical and serological criteria. This review summarizes the literature regarding animal models of APS. Animal models of this syndrome help to elucidate pathogenic roles of the characteristic antiphospholipid antibodies in pregnancy morbidity, vascular thrombosis, neurologic disease and atherosclerosis. Furthermore, these models also provide measures to evaluate novel therapies for APS. These include bone-marrow transplantation, intravenous immunoglobulin, anticoagulation, interleukin-3, in addition to other therapies. Experimental induction and treatment of APS largely contributes to our understanding of the disease and to better management of its clinical characteristics.

Adjuvants, Immunologic↗
PubMed2001

Catastrophic antiphospholipid syndrome: remission following leg amputation in 2 cases.

OBJECTIVE: The antiphospholipid syndrome is characterized by venous and arterial thrombotic events that are often recurrent, thrombocytopenia, recurrent fetal loss, and elevated titers of antiphospholipid antibodies. A subtype of patients with a particularly overwhelming clinical picture has been termed catastrophic antiphospholipid syndrome (CAPS). In this report, we present 2 patients who exhibited a similar multisystem disorder associated with gangrenous changes in the lower extremities. METHODS: Two patients with CAPS are presented, highlighting the impact of this disorder on the patients and the response to various therapeutic modalities. RESULTS: Both patients had pulmonary, cardiac, cutaneous, and neurologic findings consistent with CAPS. In addition, they had large purulent leg ulcers associated with livedo reticularis. Amputation of the legs in each case induced remission of the systemic illness. CONCLUSIONS: We believe that infection plays a significant role in the pathogenesis and amplification of the antiphospholipid syndrome. In certain patients, this association probably is mediated via immune mechanisms, which also enhance the genesis of atherosclerosis. After the foci of infection (suppurative leg ulcers) were removed, the underlying illness improved. These case studies provide an opportunity to study the interrelationship between several confounding factors that converge and lead to the development of this autoimmune condition.

Amputation, Surgical↗
PubMed2001

Anti-endothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknown etiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)2 antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in the culture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.

Antibody Specificity↗
PubMed2001

The association between anti-thyroid antibodies and pregnancy loss.

The incidence of thyroid autoantibodies in women with recurrent fetal loss, infertility or women who miscarried appears to be increased compared with controls of reproductive age without previous abortions. There are few working hypotheses concerning the asociation between anti-thyroid antibodies and the increased risk for pregnancy loss. The first hypothesis suggests that women with high titers of anti-thyroid antibodies have underlying very mild thyroid "under function". Another theory views the anti-thyroid antibodies as simply secondary markers of a predisposition of autoimmune disease rather than the actual cause of pregnancy loss. An evolutionary explanation suggests that reproductive problems in women with high titers of autoantibodies exist in order to prevent the transmission of autoimmune genes to the next generation. The reason for the association between pregnancy loss and thyroid immunity is still not clear. The working hypotheses above supply multi-factorial explanations, which could act together, may even be in synergy, as the propulsion for the pregnancy loss. Until today the mechanism by which anti Tg are responsible for pregnancy loss is not clear. Induced animal models with high titier of anti Tg could provide direct evidence for the pathogenic role of anti-thyroid antibodies and the mechanism that is responsible for the pregnancy loss in autoimmune thyroiditis. In the current presentation we describe data concerning the association between anti-thyroid antibodies and pregnancy loss, and hypothesis which explains this association.

Abortion, Spontaneous↗
PubMed2001

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.

OBJECTIVES: To review the autoimmune and rheumatic manifestations of patients with malignancy. METHODS: A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. RESULTS: Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. CONCLUSION: Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

Antibodies, Antinuclear↗
PubMed2001

Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies.

BACKGROUND: Autoimmune factors have been shown to play a role in atherosclerosis. The aim of this study is to correlate 5 autoantibodies (anticardiolipin, anti-CL, beta2-glycoprotein-I, beta2GPI, phosphatidylcholine, oxidized low-density lipoprotein, oxLDL, endothelial cell) with the presence of coronary heart disease, angiographic findings, and with coronary artery calcification. METHODS: The levels of the 5 autoantibodies and a control antifibroblast line of 126 coronary heart disease patients and 20 healthy controls were measured. Fifty-one patients underwent coronary angiography, and 98 patients had coronary artery calcium determination using spiral computerized tomography (dual mode). RESULTS: Levels of 3 autoantibodies (anti-CL, beta2GPI, oxLDL) were significantly elevated in coronary heart disease patients compared with controls (p < 0.001, p = 0.001, p < 0.001, respectively). Within the subgroup of patients with significant coronary artery stenosis, anti-CL antibodies were also elevated (p = 0.008). No correlation was found between anti-CL, and anti-beta2GPI autoantibody levels and coronary calcium scores as measured by spiral computerized tomography. However, anti-oxLDL antibodies were raised in patients with no calcification detected by spiral computerized tomography, compared with the patients with any coronary calcification (p = 0.046). CONCLUSION: Anti-CL, beta2GPI and oxLDL antibodies are elevated in coronary heart disease patients regardless of coronary calcification.

Aged↗
PubMed2001

Adverse effects of intravenous immunoglobulin therapy in 56 patients with autoimmune diseases.

OBJECTIVE: To test the adverse effects and viral safety of intravenous immunoglobulin (IVIg) use in autoimmune diseases. METHODS: Fifty-six patients with various autoimmune diseases who were treated with one to six IVIg courses were evaluated for the presence of adverse effects following IVIg therapy and were screened before and after the treatment for the presence of serum human immunodeficiency virus antibodies, hepatitis C virus antibodies, and hepatitis B surface antigen. RESULTS: Among the 56 patients, 20 (36%) had at least one adverse effect following at least one of the treatment courses. These included headache, low-grade fever, chills, anemia, low-back pain, transient hypotension, nausea, intensified perspiration, and superficial and deep vein thromboses. Whereas the presence of adverse effect to IVIg was unrelated to either the clinical response to the treatment or to the nature of the autoimmune disease, the occurrence of an adverse effect in the first treatment course was significantly associated with a greater chance for an adverse effect in the subsequent courses. No transmission of any of the three viral agents examined could be detected. CONCLUSIONS: Although IVIg use in autoimmune diseases is associated with adverse effects in about one third of the patients, these effects are usually mild and transient. Patients who develop adverse effects during the first treatment course may be at increased risk of adverse effects during the subsequent IVIg courses.

Adolescent↗
PubMed2001

High-dose intravenous immunoglobulins for lupus nephritis--a salvage immunomodulation.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a great diversity of clinical manifestations which is difficult to manage. IVIGs represent promising immunoregulatory agents with the ability to control SLE without subsequent predisposition to infectious complications. Despite the implied risk of developing renal failure due to IVIG, considerable beneficial effects on lupus nephritis are reported. In this review, the clinical and adverse effects, and mechanism of action, with special emphasis on modulation, of idiotypic network is discussed.

Humans↗
PubMed2001

Antiphospholipid syndrome induced by HIV.

A 24-y-old male who developed necrotic lesions on the lower extremities together with testicular thrombosis necessitating orchiectomy, demonstrated high level IgG anticardiolipin (aCL) associated with acute HIV infection. This is one of the first cases describing a close relationship between viral infection and the classic antiphospholipid syndrome (APS). It is well documented that HIV patients may produce antiphospholipid antibodies (aPL), but the full-blown picture of the APS is distinctly uncommon with HIV or any other viral infection, possibly due to the overproduction of the IgM isotype rather than IgG aCL as in this case. The induction of thrombosis following infections has been well described in patients with catastrophic antiphospholipid syndrome (CAPS) but not in patients with the 'classic or simple' APS.

Adult↗
PubMed2001

Vaccination and systemic lupus erythematosus: the bidirectional dilemmas.

Vaccination has been perhaps the most important achievement in medicine of the last century. A hoard of infectious diseases that used to claim the lives of many, especially children, have been prevented and some even eradicated. However, it is possible that within this gift there is hidden a 'Trojan Horse'. During the last decade increasing numbers of reports regarding possible autoimmune side effects of vaccination, have been published. The existing data does not link the vaccines and the autoimmune phenomena observed in a causal relationship, nevertheless a temporal connection has been described. In this article we wish to address in particular the possible link between vaccines and systemic lupus erythematosus (SLE), namely two aspects of this inter-relationship: the occurrence of SLE following vaccination and outcome of immunization of known SLE patients.

Hepatitis B Vaccines↗
PubMed2001

Diet and lupus.

The effect of dietary modifications has been extensively studied in lupus animal models. Calorie, protein, and especially fat restriction, caused a significant reduction in immune-complex deposition in the kidney, reduced proteinuria and prolongation of the mice's life span. The addition of polyunsaturated fatty acids (PUFAs), such as fish oil or linseed oil, was also related to decreased mice morbidity and mortality in animal models of lupus and of antiphospholipid syndrome. PUFAs such as eicosapetaenoic acid (EPA) and docosahexaenoic acid (DHA) competitively inhibit arachidonic acid with a resultant decrease in inflammatory eicosanoids and cytokines. Human studies support the effect of a PUFAs-enriched diet, both scrologically and clinically. Large scale clinical studies are needed to confirm the primary results.

Animals↗
PubMed2001

Azathioprine therapy for patients with systemic lupus erythematosus.

Azathioprine is the only purine analog that is widely used for the management of systemic lupus erythematosus (SLE). For SLE patients without renal involvement, it is given to those patients who require a maintenance dose of 15 mg or higher of prednisone and for those who experience recurrent flares. Azathioprine in combination with steroids may be given to a large number of patients with lupus nephritis. It is also effective for patients with skin lesions, pneumonitis, thrombocytopenia or hemolytic anemia. Azathioprine may be used during pregnancy but not during lactation. It has not been shown to increase the risk for the development of malignancies among patients with SLE.

Azathioprine↗