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Biomedical subjects

Yehuda Shoenfeld

Publications and source records attributed to Yehuda Shoenfeld.

At least 55 records · Page 3Linked to original sources
PubMed2005

The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome.

Thrombocytopenia is frequently found in patients with the antiphospholipid syndrome (APS), yet data concerning clinical associations of thrombocytopenia in patients with APS are still scarce. We evaluated possible associations between thrombocytopenia and various APS-related manifestations in a large group of APS patients. Three hundred and seven APS patients were retrospectively evaluated, 259 women and 48 men. Most patients had primary APS (PAPS) (n=173, 56.1%). APS was associated with systemic lupus erythematosus (SLE) in 104 patients (33.9%). All patients underwent detailed medical interview and routine physical examination. Further data were obtained from patients' medical files regarding the expression of various clinical manifestations of the disease. There were 90 patients with thrombocytopenia (29.3%), the rate was significantly higher in SLE compared to PAPS patients (41.9% vs. 23.1%, p=0.001). Similar rates of thrombocytopenia were found in male (29.2%) and female (29.3%) patients. Significant associations were found between thrombocytopenia and cardiac valves thickening and dysfunction, epilepsy, chorea, arthritis, livedo reticularis and skin ulcerations. In contrast, the rates of thrombotic episodes as well as obstetric complications were similar in patients with and without thrombocytopenia. Our data suggest the presence of thrombocytopenia may be a risk factor for cardiac, neurological, articular and cutaneous complications in APS.

Abortion, Habitual↗
PubMed2005

Hypersensitivity to mycophenolate mofetil in systemic lupus erythematosus: diagnostic measures and successful desensitization.

Despite therapeutic advances in the treatment of systemic lupus erythematosus (SLE), several patients are still afflicted with severe and uncontrolled symptoms. Recently, mycophenolate mofetil (MMF) has been introduced in the treatment of SLE, with a significant therapeutic benefit, and minor side effects have been reported. Data on the adverse effects of MMF in SLE are lacking. We present an SLE patient who developed urticaria during MMF treatment. Rechallenge with MMF established the diagnosis of MMF-induced urticaria. As MMF was considered a necessary therapy, a desensitization protocol was devised, which successfully induced tolerance to MMF. This is the first published protocol for MMF desensitization, which induced tolerance in an SLE patient previously reacting with generalized urticaria.

Desensitization, Immunologic↗
PubMed2005

Intravenous immunoglobulin for immunomodulation of systemic lupus erythematosus.

Intravenous immunoglobulin (IVIg) is used for replacement therapy in immunodeficiency states and for immunomodulation of various autoimmune diseases. Several case reports and series support a beneficial role of IVIg in systemic lupus erythematosus (SLE), both as salvage immunotherapy and in control of disease activity in general and amelioration of classical disease manifestations. Further, lupus nephritis can also be treated usually successfully with IVIg. A few questions remain unanswered as to the appropriate therapeutic dosage and the clinical manifestations that can be best treated with IVIg.

Glomerulonephritis↗
PubMed2005

2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005.

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.

Autoimmunity↗
PubMed2005

B cell depletion in autoimmune rheumatic diseases.

Rituximab is a chimeric mouse-human monoclonal antibody, which binds to CD20, a B cell surface marker, leading to cell death by complement induced lysis and apoptosis. Since the introduction of this drug in the treatment of non-Hodgkin lymphoma, its applications have been extended to autoimmune diseases. This review summarizes the actual possible uses of this novel immune system targeted drug, and explains the mechanism of B cell depletion in autoimmune diseases.

Animals↗
PubMed2005

Neuropsychiatric features of systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well known complication of systemic lupus erythematosus that remains a significant source of morbidity and mortality. Fortunately, advances in neuroimaging techniques and cognitive testing have improved the diagnosis of this disease and allowed earlier and more successful therapeutic intervention. Further, the association of NPSLE with the anti-phospholipid syndrome, other autoantibodies and inflammatory cytokines have also provided clues to the diagnosis and pathophysiology. Treatment of NPSLE is largely symptom based with outcome based on appropriate diagnosis.

Humans↗
PubMed2005

Thrombocytopenic conditions-autoimmunity and hypercoagulability: commonalities and differences in ITP, TTP, HIT, and APS.

Immune thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), heparin-induced thrombocytopenia (HIT), and antiphospholipid syndrome (APS) are clinical conditions associated with significant morbidity and mortality. These well-defined clinical syndromes have in common several properties: (1) their pathogenesis is immune mediated, specifically by autoantibodies; (2) thrombocytopenia is a hallmark in these four conditions; (3) except for the case of ITP, platelet and endothelial cell activation occurs in TTP, HIT, and APS, resulting in a prothrombotic state and an increased risk of thrombosis. Although these four immune-mediated syndromes are well-defined diseases, several case reports and studies have documented the association of two diseases in the same patient, illustrating the concept of the kaleidoscope of autoimmunity.

Autoimmunity↗
PubMed2005

Increased platelet deposition on extracellular matrix under flow conditions in patients with antiphospholipid syndrome who experience thrombotic events.

OBJECTIVE: To assess platelet function under defined flow conditions in patients with antiphospholipid syndrome (APS) and to correlate the results with thrombotic complications and the presence of subsets of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), and/or anticardiolipin antibodies (aCL). METHODS: We studied 88 randomized APS patients with or without a history of thrombosis. Seventeen patients with other thrombosis (no APS) and 26 healthy subjects served as controls. Platelet adhesion and aggregation on the extracellular matrix were measured with a cone-and-plate(let) analyzer (CPA) by examining the percentage of total area covered with platelets (surface coverage [SC]) and the mean size of surface-bound objects (average size [AS]) and were compared with platelet responses to different ADP concentrations by conventional aggregometry. RESULTS: Under defined flow conditions, SC and AS were significantly higher for venous thrombosis and arterial thrombosis in APS patients compared with no thrombosis, other thrombosis, and healthy control groups. The increased platelet adhesion and aggregation in APS patients with thrombotic events was associated with higher levels of von Willebrand factor (vWF) antigen (mean +/- SD 230.6 +/- 51.2%) and ristocetin cofactor activity (181.0 +/- 36.0%). No change in CPA and vWF parameters was found in APS patients with positive results for aPL who did not undergo thrombotic events or in patients with other thrombosis. The CPA parameters were neither associated with the high response of platelets to ADP nor associated with the presence of LAC, aCL, or both. The CPA parameters were similarly increased irrespective of aspirin use. The results suggest that the increased adhesion properties of platelets in APS patients could be mediated by high levels and activity of vWF. This complements the known ability of APS antibodies to enhance platelet response to agonists in conventional aggregometry. CONCLUSION: The CPA test was found to be valuable in differentiating APS patients with and without thrombotic complications.

Adult↗
PubMed2005

Precocious intima-media thickening in patients with primary Sjögren's syndrome.

OBJECTIVE: Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sjögren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women. METHODS: Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls. RESULTS: The patients had a higher IMT than did the controls at both the carotid (mean +/- SD 0.82 +/- 0.24 mm versus 0.63 +/- 0.20 mm; P < or = 0.001) and the femoral (0.81 +/- 0.26 mm versus 0.67 +/- 0.23 mm; P < or = 0.019) levels, and had a higher prevalence of carotid intima-media thickening (49% versus 11% of controls; P < or = 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening. CONCLUSION: Subclinical ATS was evident in about one-half of the patients with SS. Its association with some features typical of connective tissue diseases, such as the presence of anti-SSA and leukopenia, suggests that the immune dysregulation characterizing this autoimmune disorder may play a key role in inducing early ATS.

Adult↗
PubMed2005

Protective molecules--C-reactive protein (CRP), serum amyloid P (SAP), pentraxin3 (PTX3), mannose-binding lectin (MBL), and apolipoprotein A1 (Apo A1), and their autoantibodies: prevalence and clinical significance in autoimmunity.

Apoptotic defects and impaired clearance of cellular debris are considered key events in the development of autoimmunity, as they can contribute to autoantigen overload, and may initiate an autoimmune response. The pentraxins are a group of highly conserved proteins including the short pentraxins, C-reactive protein (CRP) and serum amyloid-P (SAP), and the long pentraxin-3 (PTX3), which are all involved in innate immunity and in acute-phase responses. Mannan-binding lectin (MBL) is an activator of the complement system, and Apolipoprotein A-1 (Apo A-1) is pivotal in the cholesterol homeostasis and has anti-inflammatory properties. In addition to their role in innate immunity and inflammation, each of these five proteins participates in the removal of damaged and apoptotic cells. In this review, we discuss the clinical significance of different levels of these proteins, their role in the induction or protection from autoimmunity, and the presence of specific autoantibodies against them in the different autoimmune diseases.

Animals↗
PubMed2005

Statins and autoimmune diseases.

Inhibitors of 3-hydroxy-3methylglytaryl coenzyme A (HMG-CoA) reductase or statins are effective lipid lowering drugs widely used in cardiovascular disease. In the recent years, pleotropic effects of statins have been reported, which include anti-inflammatory and immunomodulatory properties. This review discusses the anti-inflammatory and immunomodulatory roles of statins and their possible use for the treatment of other inflammatory diseases or conditions with the involvement of the immune system.

Animals↗
PubMed2005

TNF-alpha, rheumatoid arthritis, and heart failure: a rheumatological dilemma.

Cardiovascular disease (CVD) is responsible for 35-50% of rheumatoid arthritis (RA) deaths, whereas, in the general UK adult population, coronary heart disease is responsible for 1/4 deaths in males and 1/5 deaths in female. This increased risk may be attributable to RA-specific risk factors such as hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or to morbidity related to medications and high levels of tumor necrosis factor-alpha (TNF-alpha). The possible roles of TNF-alpha in the development of atherosclerosis include the recruitment of inflammatory cells to the site of injury or the promotion of adverse vascular smooth muscle cell remodelling. TNF-alpha may also act as a proinflammatory factor in plaque rupture. Anticytokine therapy could prove beneficial in the treatment of patients with heart failure. While early studies supported this hypothesis, anti-TNF strategies have not demonstrated salutary benefits in large multicenter randomized and placebo-controlled clinical trials in patients with symptomatic heart failure. There is a variety of possible explanations for the failure of anti-TNF therapy: (1) TNF antagonism has untoward effects in the setting of heart failure; (2) the biological agents used in the trials were intrinsically toxic; (3) sex and race may have important implications in the outcome after anticytokine therapy; (4) the TNF-alpha protein contains a polymorphism, and, in fact, genoma plays a role in modifying the pharmacologic response to anticytokines; (5) anti-TNF-alpha approaches could have had pharmacodynamic interactions with other heart failure medications; and (6) the patients in these trials may have been inappropriately selected. These disappointing results may determine controversial attitude in the long-term treatment with anti-TNF agents in RA or Crohn's disease. The effects of TNF-alpha blockers on incident cases of congestive heart failure (CHF) in RA are controversial. The available published data suggest the following: (a) RA patients with history of CHF and a concomitant indication for the use of TNF-alpha blockers do not need a baseline cardiac evaluation to screen for heart failure; (b) patients with well-compensated mild CHF New York Heart Association (NYHA) classes I and II and a concomitant indication for the use of TNF-alpha blockers should be evaluated at baseline and then be closely monitored for any clinical signs of worsening heart failure; and (c) patients with (NYHA) class III or IV heart failure should not be treated with TNF-alpha blockers in any case.

Adalimumab↗
PubMed2005

The neuroendocrine-immune interactions in systemic lupus erythematosus: a basis for understanding disease pathogenesis and complexity.

Much progress has been made in the understanding of the impact of the neuroendocrine immune interactions and the pathogenic role in systemic lupus erythematosus, clinically and at the molecular level. This article focuses on the intertwining networks that involve the hypothalamic-pituitary-adrenal axis, cytokines within the central nervous system, and the sympathetic system. Hormones (estrogen, prolactin, gonadotropin-releasing hormone, and leptin) play an important role as immunomodulatory agents.

GTP-Binding Proteins↗