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Biomedical subjects

Yehuda Shoenfeld

Publications and source records attributed to Yehuda Shoenfeld.

At least 91 records · Page 5Linked to original sources
PubMed2005

Early atherosclerosis in rheumatoid arthritis: effects of smoking on thickness of the carotid artery intima media.

This study was designed to compare intima media thickness (IMT) of the carotid arteries among rheumatoid arthritis (RA) patients and controls and to determine whether disease-associated characteristics, smoking, and other classic risk factors for atherosclerosis are associated with IMT values. IMT was measured in the carotid arteries of 101 RA patients and 75 control subjects. The IMT was evaluated in the common carotid (CC), carotid bifurcation (BI), and internal carotid (IC). Eight IMT values were calculated including four mean and four maximal values of CC, BI, IC, and carotid artery (C). The following data were obtained for every patient: age, sex, body mass index (BMI), presence of erosions, extra-articular manifestations, rheumatoid factor, medications, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, daily number of cigarettes, number of smoking years, family history of cardiovascular diseases (CVD), and erythrocyte sedimentation rate (ESR) levels. RA patients had significantly higher mean-BI IMT than controls (1.02 mm vs. 0.89 mm; P < 0.01), higher incidence of increased mean-BI IMT and max-BI IMT, but lower incidence of increased max-IC IMT than controls. Factors significantly associated with IMT in the controls were age, BMI, and hypertension, whereas factors significantly associated with IMT in RA patients were age and smoking status. Mean carotid IMT was associated with all characteristics related to smoking in RA patients. Current smokers had higher mean carotid IMT and internal carotid artery IMT than former smokers. RA is associated with higher carotid artery bifurcation IMT. The profile of factors associated with IMT values is different between RA patients and controls. Smoking is an important factor augmenting early atherosclerosis in RA patients.

Adult↗
PubMed2005

Prevalence of antiphospholipid and antioxidized low-density lipoprotein antibodies in rheumatoid arthritis.

Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.

Antibodies, Anticardiolipin↗
PubMed2005

The role of innate and adaptive immunity to oxidized low-density lipoprotein in the development of atherosclerosis.

Atherosclerosis is a chronic inflammatory process of the arterial wall associated with systemic and local immune responses to various antigens, oxidized low-density lipoprotein (oxLDL) being the most significant. Both IgM and IgG antibodies to oxLDL are produced during atherosclerosis. Some studies have shown that elevated levels of antibody to oxLDL correlate with the degree of atherosclerosis. Other studies reported that immunization of experimental animals with oxLDL induces high levels of antibodies to oxLDL, with decreased atherosclerosis, suggesting that the immune response to oxLDL may be antiatherogenic. The accelerated development of atherosclerosis has been observed in patients with systemic autoimmune diseases. In patients with antiphospholipid syndrome (APS), beta2-glycoprotein I (beta2GPI) is a major antigenic target for anticardiolipin antibodies (aCLs). We recently reported that oxLDL interacts with beta2GPI via oxLDL-derived specific ligands, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) to form complexes. In vitro, anti-beta2GPI autoantibodies bind to oxLDL/beta2GPI complexes that are actively taken up by macrophages via Fcgamma receptors. Circulating oxLDL/beta2GPI complexes were detected in patients with systemic lupus erythematosus (SLE) and APS, at higher levels than in healthy individuals. Autoantibodies against these complexes were also present; however, IgG anti-oxLig-1/beta2GPI antibody levels in SLE patients with APS were significantly higher than those in SLE patients without APS and those in healthy individuals.

Animals↗
PubMed2005

Fermented wheat germ extract (Avemar) in the treatment of cancer and autoimmune diseases.

Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.

Animals↗
PubMed2005

Immunomodulatory effects of intravenous immunoglobulins as a treatment for autoimmune diseases, cancer, and recurrent pregnancy loss.

Intravenous immunoglobulin (IVIG) is a safe preparation, made of human plasma of thousands of healthy donors. The fascinating history of gamma globulin therapy begins in 1930 when Finland treated pneumococcal pneumonia patients with equine serum, which prolonged their survival from pneumonia. Since then, significant breakthroughs were achieved by Cohn, Bruton, Imbach, and others, whose clinical contribution to the world of medicine was of great importance. Originally IVIG was used to treat immunodeficiencies. Later on the use of IVIG extended to autoimmune diseases as well. The efficacy of IVIG has been established only in several autoimmune diseases; clinical reports of trials, series, and case reports indicate significant improvement in many more autoimmune diseases. IVIG have also showed antimetastatic effects in a variety of cancer cell lines, as well as in a few case reports. The efficiency of IVIG has also been observed in recurrent pregnancy loss (RPL), either as a result of an autoimmune disease or spontaneous. Several attempts were made to discover the immunomodulatory effects of IVIG, but it is still not fully understood. Clearly IVIG has multiple mechanisms of actions, which are thought to cooperate synergistically. One of the main mechanisms of actions of IVIG is its ability to neutralize pathogenic autoantibodies via anti-idiotypic antibodies within IVIG preparation. The ability of IVIG to neutralize pathogenic autoantibodies is of great importance in many autoimmune diseases, as well as in RPL. In cancer cell lines, IVIG modulates the immune system in a few ways, including the induction of IL-12 secretion, which consequently activates natural killer cells, and the induction of expression of proapoptotic genes only in cancer cells. Side effects from IVIG are rare and mostly mild and transient. More importantly adverse effects can be minimized by administration to a selective patient population in a proper way: slow infusion rate of 0.4 g/Kg body weight IVIG for 5 consecutive days, given in monthly cycles. The only downside of IVIG therapy is its high price. Therefore, clinicians should balance efficiency versus cost in deciding whether or not to treat certain conditions with IVIG.

Abortion, Habitual↗
PubMed2005

Response of vasculitic peripheral neuropathy to intravenous immunoglobulin.

Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it responds to corticosteroids therapy, but in certain cases it may resist corticosteroid or immunosuppressive treatment, or both. The objective of this study is to present case reports of patients who exhibited various inflammatory diseases, accompanied with vasculitic peripheral neuropathies, for which intravenous immunoglobulin (IVIg) was used for treatment. The study included 10 patients with the following: Sjögren's syndrome (1), systemic lupus erythematosus (2), vaccination-induced vasculitis (1), Churg-Strauss vasculitis (1), mixed cryoglobulinemia (2), polyarteritis nodosa (1), sarcoidosis (1), and scleroderma (1). All developed vasculitic peripheral neuropathy and were treated with 1-13 cycles of high-dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. Results showed that in all but two patients (mixed cryoglobulinemia associated with hepatitis C and sarcoidosis), neuropathy improved or completely resolved after IVIg treatment. In conclusion, IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment in patients for whom conventional treatment is contraindicated, or for patients in whom conventional treatment has failed.

Child↗
PubMed2005

Intravenous immunoglobulin treatment for fibrosis, atherosclerosis, and malignant conditions.

We describe our experience with intravenous immunoglobulin (IVIg) treatment in fibrotic conditions and our results and experience with the effect of IVIg therapy to prevent metastases in malignancy. We have delineated the mechanisms by which IVIg can affect atherosclerosis (i.e., effect on MMP-9, antiidiotypes to anti-OxLDL), which led to reduced atherosclerosis in animal models. The effect of IVIg on skin fibrosis was assessed in a murine model of scleroderma-like disease. Collagen expression was decreased in the skin of mice treated with mouse IVIg, associated with decreased type I collagen gene expression, and accompanied by inhibition of transforming growth factor (TGF)beta and interleukin (IL)-4 secretion by splenocytes. We also described a favorable response to IVIg treatment in patients with either systemic sclerosis or myelofibrosis. The administration of IVIg to mice inoculated with melanoma or sarcoma cells induced a statistically significant inhibition of metastatic lung foci and prolongation of survival time. IVIg was found to stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine. Positive staining of the cytoplasm, cell membrane, and nuclear membrane of several types of malignant tumors by IVIg was immunohistochemically demonstrated.

Animals↗
PubMed2005

Intravenous immunoglobulin: adverse effects and safe administration.

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Acute Kidney Injury↗
PubMed2005

Facing the enigma of immunomodulatory effects of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is a safe remedy for a number of conditions; it is produced from human plasma of thousands of healthy donors. The therapeutic effect of IVIg lies within its content. IVIg contains natural antibodies, which are more polyreactive than immune antibodies, including immunoglobulin G antibodies against endogenous and exogenous antibodies, immunomodulating peptides, and varies cytokines. Beneficial effects of IVIg have been established in immunodeficiencies, as well as in some autoimmune diseases. Also, numerous therapeutic effects of IVIg have been reported over the years in varies autoimmune diseases, recurrent pregnancy loss, and cancer. Many proposed immunoregulatory mechanisms of action of IVIg have been suggested. Some of them have been proven, others are still an enigma, at least in part. Some of these mechanisms entail (a) Fc-receptor blockade; (b) neutralization of pathogenic autoantibodies via idiotypic and anti-idiotypic antibodies; (c) effects on the Fas apoptotic pathway via agonistic and antagonistic anti-Fas autoantibodies; (d) regulation of complement components; (e) modulation of cytokine secretion; (f) hindrance of natural-killer cell activity; (g) inhibition of matrix metalloproteinase-9; (h) suppression of NFkB activation and IkB degradation; (i) G1 cell cycle arrest; (j) prevention of tumor growth; (k) decrease in leukocyte recruitment; (l) attenuation of T-cell stimulation; (m) effects on antibody kinetics; and (n) effects on dendritic cells. The variant mechanisms of IVIg are believed to cooperate in a synergistic way, which all together point to IVIg as a therapeutic preparation with anti-inflammatory, antiself-reactivity, antimetastatic, and embryo-protective effects. This article reviews several main mechanisms of IVIg in order to shed some light on the set of therapeutic effects of IVIg, which are not yet fully understood.

Animals↗
PubMed2005

Toward molecular targeting with specific intravenous immunoglobulin preparation.

Intravenous immunoglobulin (IVIg) is used successfully for therapy of inflammatory and autoimmune diseases, especially in cases of conventional therapy resistance. Within the broad spectrum of immunoregulatory activities of IVIg in vitro and in vivo, the anti-idiotypic activity neutralizing the related idiotypes is one of the main mechanisms. Furthermore, IVIg addresses integrins associated with inflammation and immune response thrombosis, such as the RGD (Arg-Gly-Asp) motif, expressed on a large number of cell surface and matrix proteins. In addition, during the last years, anti-Fas activity of IVIg was reported. We fractionated IVIg specific preparation (sIVIg) based on the multispecificities of the IVIg compound. We have generated an IVIg fraction that will show specific activity for lupus idiotypes in vitro. In NZBxW.F1 mice, results showed 200 times more beneficial effect. Using a peptide phage display library technology, we have identified a panel of lupus-related synthetic idiotypes that are mimetics of the idiotypes presented in patients with systemic lupus erythematosus. A column composed of these synthetic lupus-related idiotypes was used to prepare a large amount lupus-specific IVIg. Using the same approach, we prepared anti-anti-beta-2-glycoprotein-I (beta2GPI) specific IVIg for antiphospholipid syndrome (APS). This APS-specific IVIg reduced the fetal loss induced by anti-beta2GPI antibodies by improving the implantation process in a mouse model. Others prepared specific preparations of IVIg to RGD or for Fas. The molecular targeting with specific IVIg may be used for therapeutical purposes, using a smaller amount of IVIg, and targeting more specifically autoimmune diseases, thrombosis, or inflammatory condition.

Animals↗
PubMed2005

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Adult↗
PubMed2005

Intravenous immunoglobulin and Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a relatively common, potentially lethal disease of a presumed autoimmune origin, known to cause a progressive flaccid paralysis. The treatment of GBS consists of both supportive and immunomodulatory treatments, among which intravenous immunoglobulin (IVIg) and plasma exchange (PE) are considered most effective. A number of randomized, controlled studies have shown IVIg to be at least as effective as PE in the treatment of GBS, and in some cases superior. Moreover, IVIg has been found to be safer than PE, having a lower frequency of multiple complications. IVIg has also been found to be both effective and safe in the treatment of pediatric patients with GBS. Thus, its efficacy, safety, and availability make IVIg the treatment of choice in many patients with GBS.

Adult↗
PubMed2005

Uncovering the hidden potential of intravenous immunoglobulin as an anticancer therapy.

Intravenous immunoglobulin (IVIg) is a safe preparation made from human plasma. The original concept of IVIg as an anticancer drug was built up over the years, after numeral reports were accumulated indicating cancer regressions after IVIg administration. Because IVIg is basically an established remedy for immunodeficiencies and several autoimmune diseases, the association between beneficial effects in cancer patients after IVIg was first seen in patients who had both cancer and autoimmune or immunodeficiency diseases. Interestingly, cancer and autoimmunity share several common features, which together enhance the notion of using IVIg to treat cancer. Several studies tested the broad range of the antimetastatic effects of IVIg. IVIg was found to operate in many different and complex ways, among them (a) induction of interleukin-12 secretion, leading to natural-killer-cell activation; (b) inhibition of matrix metalloproteinase-9 mRNA expression; (c) suppression of tumor cell growth; (d) hindrance of nuclear factor kappaB activation and IkappaB degradation; and (e) G1 cell-cycle arrest. In conclusion, IVIg is a potential anticancer treatment for several reasons: (a) the bidirectional relationship between cancer and autoimmunity; (b) the apparent association between cancer regression and IVIg administration; (c) a variety of anticancer effects of IVIg observed; and (d) IVIg is considered to be a safe preparation with minimal side effects. Obviously, prospective controlled studies that will establish the antitumor effects of IVIg are needed.

Animals↗
PubMed2005

Intravenous immunoglobulin and atherosclerosis.

Several inflammatory and immunological factors have been established as important contributors to atherogenesis. Among these, oxidized low-density lipoprotein (oxLDL) play a central role in the initiation and progression of atherosclerotic lesions. In atherosclerotic lesions, oxLDL was also found to co-localize with beta2-glycoprotein I (beta2-GPI). Immunoglobulin (Ig)G autoantibodies against beta2-GPI complexed with oxLDL are pro-atherogenic because they increase uptake of the complexes by macrophages. In contrast, IgM natural anti-oxLDL antibodies derived from atherosclerosis-prone apolipoprotein E (ApoE) deficient mice reduced incidence of atherosclerosis. Such anti-oxLDL antibodies have been found in humans, and the accumulating evidences seem to support the idea that anti-oxLDL antibodies have a protective role for atherogenesis. Intravenous immunoglobulins (IVIgs) contain natural anti-oxLDL antibodies and infusion of IVIg into ApoE-deficient mice has been reported to decrease atherosclerosis. The anti-atherogenic property of IVIg may be derived from non-antigen-specific antibody binding to FCgamma receptors, which blocks foam cell formation of macrophages. Several other possible mechanisms are also discussed.

Animals↗
PubMed2005

Intravenous immunoglobulin and fibrosis.

Fibrosis is a pathological process that includes scar formation and overproduction of extracellular matrix by the connective tissue as a response to tissue damage. Pathologies include pathological scarring as colloid and hypertrophic scars in the skin, cirrhosis of liver and gallbladder, pulmonary and bone-marrow fibrosis, and scleroderma. The molecular process is not different from normal formation of connective tissue and extracellular matrix in the normal organs. Major profibrotic agents are type 2 CD4-positive lymphocytes, CD40 receptor and ligand interaction, and the cytokines interleukin-4, transforming growth factor-beta, and platelet-derived growth factor. The major antifibrotic agent is interferon-gamma. Fibrosis was considered an irreversible process, at least clinically, and is still usually treated by anti-inflammatory and immunosuppressive agents. No proven antifibrotic therapy has shown efficacy in ameliorating clinical fibrosis. Intravenous immunoglobulin has a very good safety profile, and was found to be an ameliorating agent for several fibrotic diseases, and hence could be a drug of choice to these patients and improve their quality of life.

Animals↗
PubMed2005

Intravenous immunoglobulin and recurrent pregnancy loss.

Intravenous immunoglobulin (IVIg) has been used to prevent pregnancy loss, in unexplained recurrent miscarriage, and in antiphospholipid syndrome (APS). When used on an unselected population with recurrent miscarriage, IVIg has not been shown to improve the live birth rate. However, when patients are selected for poor prognosis or autoimmune phenomena, IVIg has been shown to be effective. This article discusses the possible immune mechanisms by which IVIg may act and the effect of confounding factors such as embryonic chromosomal aberrations or anti-beta2-glycoprotein I antibodies in APS. Hence, there may be an impression of futility, when IVIg may be highly effective in saving those pregnancies that can be saved. Additionally, in an unselected population with recurrent miscarriage, there is a relatively good prognosis for a subsequent live birth (60%). Therefore, the spontaneous prognosis must be taken into account, which has not been the case in previous trials.

Abortion, Habitual↗