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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 73 records · Page 4Linked to original sources
PubMed2004

Antiphospholipid antibodies in acute coronary syndrome.

Antiphospholipid (aPL) antibodies entailing anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) antibodies may be involved in a number of vascular diseases including coronary artery diseases (CAD) or stroke. Here we assessed the presence of aPL antibodies in acute coronary syndrome (ACS). The frequency of anti-beta2GPI antibodies was significantly higher (14.4%) in ACS in comparison to control healthy subjects (2%). In addition, serum concentrations of anti-beta2GPI antibodies were also increased in ACS. Anti-beta2GPI antibodies of the IgA isotype might be the most relevant for the onset and outcome of ACS. Regarding subclasses of ACS, anti-beta2GPI IgA antibodies were elevated in unstable angina (UA) and myocardial infarction with ST elevation (STEMI), but not in myocardial infarction without ST elevation (NSTEMI). The involvement of anti-beta2GPI antibodies in ACS was more pronounced in men than women, and in younger rather than older patients. Finally, anti-beta2GPI antibodies in ACS were associated with previous stroke, but not with hypertension or previous myocardial infarction. Thus, anti-beta2GPI antibodies may be involved in the thrombotic events underlying ACS.

Adult↗
PubMed2004

Antiphosphatidylserine antibodies and reproductive failure.

Some cases of reproductive failure with autoimmune background are characterized by the involvement of autoantibodies. This occurs mainly in patients having systemic lupus erythematosus or antiphospholipid syndrome. The autoantibodies associated with reproductive failure include: a) antibodies which directly bind phospholipid (e.g., cardiolipin, phosphatidylserine, phosphatidylethanolamine); b) antiphospholipid Abs which bind the phospholipid via phospholipid-binding glycoproteins such as beta2glycoprotein-I, annexin V and prothrombin; c) autoantibodies directed to laminin-I, actin, thromboplastin, the corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and mitochondrial antibodies of the M5 type. This paper will focus on the association of antiphosphatidylserine autoantibodies and reproductive failure. Future studies are likely to help to identify peptides resembling the epitope specificities associated with the specific clinical manifestations.

Abortion, Spontaneous↗
PubMed2004

Autoantibodies associated with reproductive failure.

Autoimmune factors are involved in some of the cases of reproductive failure. These factors entail several autoantibodies, especially in patients having systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS). These autoantibodies include mainly antibodies directed to phospholipid such as cardiolipin, phosphatidylserine, phosphatidylethanolamine or phospholipids binding glycoproteins such as beta2glycoprotein-I, annexin V, prothrombin and protein-Z. There are also some other autoantibodies directed to laminin-I, thromboplastin, mitochondrial antibodies of the M5 type, corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and more, which were also found in SLE or APS patients with reproductive failure. Moreover, the presence of additional autoantibodies directed to actin, enolase, cubilin and others, needs further investigation to support a firm association to reproductive failure in women. Future studies are likely to help to determine and expand the number of autoantibodies screened in these patients, as well as by the use of proteomics technology, to determine peptides resembling the epitope specificities associated with the specific clinical manifestations.

Abortion, Habitual↗
PubMed2004

Antineutrophil cytoplasmic autoantibodies penetrate into human polymorphonuclear leukocytes and modify their apoptosis.

OBJECTIVE: The interaction of extracellular anti-neutrophil cytoplasmic autoantibodies (ANCA) with neutrophilic granules may play an important role in the pathogenesis of ANCA-related disorders. It has been confirmed that apoptosis is an essential trigger associated with translocation of the cytoplasmic granules to the cell surface, and with the expression of ANCA antigens. Since cell penetration by autoantibodies and apoptosis may be associated processes, we tested the hypothesis that penetration of ANCA-autoantibodies into polymorphonuclear leukocytes (PMNs) has an effect on apoptosis and thereby can influence surface antigen expression. METHODS: PMNs were isolated from the blood of healthy volunteers and incubated in the presence of anti-proteinase3 (PR3) enriched IgG or normal human IgG. For each period of incubation (40 minutes or 12 hours) we evaluated: 1) PMN morphology by light microscopy (LM) and transmission electron microscopy (TEM) for general estimation of the apoptotic process, and 2) ANCA binding to the target antigen by immunogold electron microscopy (IgEM). RESULTS: Both normal and anti-PR3 IgG penetrate PMNs. The labeled PR3-ANCA were localized on PR3 granules, regardless of the granules' location within the cell, and in the sites where the PMN destruction processes were most expressed. The destructive processes showed extensive apoptotic characteristics, in contrast to PMNs penetrated by normal IgG. CONCLUSION: PR3 ANCA penetrate PMNs and, via the interaction between PR3-ANCA and PR3-containing granule components, initiate a modification of the apoptotic process.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

A medical nutriment has supportive value in the treatment of colorectal cancer.

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.

Adult↗
PubMed2003

10th International Congress on Antiphospholipid Antibodies--summary.

The 10th International Congress on Antiphospholipid Antibodies (Sicily, Italy, September 29-October 3, 2002) (Fig. 1) provided enlightening aspects on the recent developments in antiphospholipid syndrome (APS) and antiphospholipid antibodies in more than 150 lectures and posters. Researchers from all aspects of medicine attended the meeting, implicating the systemic characteristics of APS. The important breakthroughs are summarized.

Animals↗
PubMed2003

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗
PubMed2003

Antiprothrombin antibodies are associated with pregnancy loss in patients with the antiphospholipid syndrome.

OBJECTIVE: To document the clinical association between the history of pregnancy loss in patients with the diagnosis of primary or secondary antiphospholipid syndrome (APS) and the presence of different antiprothrombin antibody subtypes [immunoglobulin G (IgG), IgM and IgA] in a cohort of patients with APS. METHODS: Records of 170 female patients with primary APS, or APS secondary to systemic lupus erythematosus (SLE) or secondary to other autoimmune diseases were studied. RESULTS: In female APS patients with IgG antiprothrombin antibodies (n = 105) significant associations to pregnancy loss (p < 0.0001), early pregnancy loss (p < 0.0001) and a negative association to thrombocytopenia (p < 0.01) could be identified. In the group of patients with IgG antiprothrombin antibodies and at least one pregnancy (n = 84) a significant association with pregnancy loss (p < 0.005) and especially with early pregnancy loss (p < 0.0001) was demonstrated. No association with other immunoglobulin subtypes of antiprothrombin antibodies could be documented. In the subgroup of patients with primary APS and at least one pregnancy in the history, pregnancy loss (p < 0.005) and early pregnancy loss (p < 0.0001) were found to be highly associated with the presence of IgG antiprothrombin antibodies. IgG antiprothrombin antibodies represent the highest independent risk factor for pregnancy loss with an odds ratio of 4.5. There was no statistically significant association with venous or arterial thrombosis in all IgG antiprothrombin antibody positive patients. CONCLUSION: The results of this study document the association of IgG antiprothrombin antibodies with pregnancy loss and in particular early pregnancy loss in a large and well-characterized cohort of patients. We would recommend routine testing for antiprothrombin antibodies in young female patients with APS.

Abortion, Spontaneous↗
PubMed2003

Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment.

In a first study, we performed a cross-sectional analysis of urinary excretion of isoprostanes, IPF(2alpha-III) and (VI), and monocyte tissue factor (TF) antigen and activity between 11 antiphospholipid (APL) antibody-positive patients and 13 APL negative subjects. In a second study, 11 APL positive patients were randomly supplemented either with (n = 6) or without (n = 5) antioxidants (vitamin E at 900 IU day(-1), vitamin C at 2000 mg day(-1)) for 6 weeks. In a third study, TF and superoxide anion were measured in human monocytes incubated with anti-beta(2) glycoprotein 1 (beta(2)GP(1)) or control IgG, either with or without vitamin E. APL-positive patients had higher values of isoprostanes (P < 0.05) and monocyte TF antigen (P = 0.001) and activity (P = 0.0001) than APL-negative subjects. Only in APL positive patients did monocyte TF antigen correlate significantly with IPF(2alpha-III) (rho 0.79; P < 0.003) and IPF(2alpha-VI) (rho = 0.87; P < 0.0001). In patients who received antioxidant supplementation, we found a significant decrease of isoprostanes (P < 0.05) and monocyte TF antigen (P < 0.01) and activity (P < 0.007). In vitro experiments demonstrated that anti-beta(2)GP(1) antibodies dose-dependently enhanced the monocyte production of the superoxide anion and TF, which were significantly inhibited by vitamin E. This study demonstrates that in APL-positive patients, oxidative stress contributes to activate the clotting system via over-expression of monocyte TF. We suggest that anti-beta(2)GP(1) antibodies could play a pivotal role by enhancing the monocyte production of oxygen free radicals.

Adult↗
PubMed2003

Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis.

BACKGROUND: Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it is responsive to corticosteroids, but in certain cases it may be resistant to corticosteroid or immunosuppressive treatment, or both. OBJECTIVE: To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. METHODS: Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. RESULTS: In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. CONCLUSION: IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed.

Adult↗
PubMed2003

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

Adult↗
PubMed2003

Fibrosis regression induced by intravenous gammaglobulin treatment.

OBJECTIVES: To review case histories of patients in whom fibrosis played a significant role in the pathogenesis of their disease, and to determine whether intravenous gammaglobulin (IVIg) contributed to the regression of their fibrotic condition. METHODS: Eight patients with excess fibrotic reaction in the course of diverse diseases were analysed; a tendency that reverted with different IVIg treatment options. Myelofibrosis was predominant in three patients (a patient with a myeloproliferative syndrome, one with systemic lupus erythematosus, and one with Sjögren's syndrome). Three patients had scleroderma as their main feature, one patient had hepatitis C cirrhosis, and one had idiopathic thrombocytopenic purpura. RESULTS: Fibrotic excess was reduced in all the patients by IVIg treatment. In five patients the disease as a whole benefited from the infusion of immunoglobulins. CONCLUSION: IVIg may enhance resorption of fibrosis and promote healing in patients with fibrotic associated disorders.

Aged↗
PubMed2003

Asthma as a paradigm for autoimmune disease.

Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanisms in some cases, by looking at the key elements that regulate the immune response in both asthma and autoimmune conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of asthma and autoimmune conditions in the same patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in asthma, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic diseases suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T cell receptor loci have long been considered important candidates for a common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to successful treatment of asthma and autoimmune conditions.

Asthma↗
PubMed2003

Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model.

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipid syndrome (APS). Mice were immunized with either prothrombin, beta2-glycoprotein-I (beta2GPI), or beta2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1 min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibody levels directed towards their immunizing autoantigens. The groups immunized with beta2GPI or beta2GPI/prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopenia and increased fetal resorption rate. All prothrombin-immunized mice as well as most beta2GPI/prothrombin-immunized mice developed visible thrombus within the aorta. Some beta2GPI immunized mice developed very mild thrombus. None of the CFA/PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or beta2GPI/prothrombin is associated with prothrombotic activity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.

Animals↗
PubMed2003

The prevalence of coeliac disease antibodies in patients with the antiphospholipid syndrome.

High prevalence of coeliac disease (CD) has been reported in various autoimmune disorders, buthas not been studied in the antiphospholipid syndrome (APS). We aimed to establish the prevalence of CD antibodies in a cohort of APS patients, and to examine whether CD may be responsible for some of the manifestations of APS. Fifty-seven patients (47 females, 10 males) with APS were studied for clinical manifestations and serological markers of the disease, as well as the presence of anti-endomysial antibodies using an ELISA assay (EMA-ELISA). Control subjects were 171 healthy individuals, age- and sex-matched (141 females). Eight patients with APS (14%, six females) were found to have EMA-ELISA antibodies, compared with 2/141 (1.1%) of controls (P = 0.0003). Antibodies against beta2-glycoprotein-I (beta2GPI) epitopes (GRTCPKPDDLP) were more prevalent in EMA-positive patients than in EMA-negative patients (P = 0.006). Vasculitic skin lesions were significantly more common in EMA-ELISA-positive compared with EMA-ELISA-negative patients(62.5 versus 16.3%, P = 0.01). Among the skin manifestations, superficial cutaneous necrosis (37.5 versus 2%, P = 0.007) was more prevalent in EMA-ELISA-positive than in EMA-ELISA-negative patients. EMA-ELISA antibodies are common in APS, and their presence is associated with high prevalence of antibodies recognizing certain beta2-glycoprotein epitopes, and with cutaneous manifestations of APS.

Adult↗