Search PubMed⌕ Search

Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

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

Anti-ribosomal P-protein and its role in psychiatric manifestations of systemic lupus erythematosus: myth or reality?

Systemic lupus erythematosus (SLE) is an autoimmune disease that may involve the central nervous system (CNS) resulting in neuropsychiatric manifestations. The associated psychiatric disorders include depression, psychosis, mood disorders, anxiety, cognitive dysfunction, and delirium/ encephalopathy. Several autoantibodies may play a role in the pathogenesis of psychiatric complications of SLE, particularly antibodies against ribosomal P-proteins (anti-P) and possibly antibodies against endothelial cells (AECA). The reported prevalence of anti-P is highly variable in SLE patients and is dependent on different ethnic backgrounds, sensitivity and specificity of the assays employed for autoantibody detection, and the time at which sera were analysed in relation to the clinical event. Controversial data exist on the association of anti-P with psychiatric manifestations of SLE. These autoantibodies have been suggested to be specific markers of the psychiatric manifestations of SLE, particularly of the psychosis and depression, and the antibody level varied with the clinical activity of the disease. Some studies have confirmed the hypothesis of an association of anti-P antibodies with psychiatric manifestations of neuropsychiatric SLE (NPSLE) while others have disputed this relationship. This review summarizes the recent studies about relationship between anti-P antibodies and psychiatric manifestation of SLE.

Autoantibodies↗
PubMed2005

Predictive and protective autoimmunity in cardiovascular diseases: is vaccination therapy a reality?

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. Given these recent advances, various modifications of the immune system in experimental models have been proposed as therapeutic strategies, with the potential of inhibiting atherosclerosis progression. These modifications are switching the immune system (CD4+ T cells) from Th1 towards a Th2 anti-inflammatory cytokine secretion, and the induction of protective antibodies both of which may be induced by specific vaccination. Recent identification of specific immunoreactive antigenic epitopes on modified LDL, their successful implementation for immunization and the induction of atheroprotection, supports the idea that active vaccination may emerge as a novel immuno-modulating atheroprotective strategy.

Atherosclerosis↗
PubMed2005

Idiopathic recurrent acute pericarditis: familial Mediterranean fever mutations and disease evolution in a large cohort of Caucasian patients.

Idiopathic recurrent acute pericarditis (IRAP) is suspected to be an autoimmune phenomenon. We studied 46 consecutive patients. We looked for: 1) the occurrence of new diagnoses of autoimmune diseases during our follow up; 2) HLA typing; and 3) the presence of the most frequent mutations linked to familial Mediterranean fever (FMF gene or MEFV). HLA typing was done in 21 patients at loci B, DRB1, DQA1 and DQB1. MEFV gene was looked in 23 patients using specific primers. During the follow-up we made a new diagnosis of primary Sjögren's syndrome in four patients (8.7%) and of rheumatoid arthritis in one patient (2.2%). HLA B14, DRB1*01 and DQB1*0202 were significantly more prevalent, but we did not find a typical HLA typing. MEFV gene was searched: exon 10 was checked by sequence and the E148Q mutation by restriction site analysis. No mutations were found. In conclusion, the prevalence of definite immunorheumatological diseases and the absence of the mutations linked to FMF reinforce the notion that idiopathic acute recurrent pericarditis is an autoimmune condition.

Arthritis, Rheumatoid↗
PubMed2005

From rheumatic fever to Libman-Sacks endocarditis: is there any possible pathogenetic link?

The heart lesions of rheumatic fever and the heart involvement in antiphospholipid syndrome (APS), have different clinical pictures. Yet, there are several common characteristics linking both diseases: 1) central nervous system (CNS) and heart involvement; 2) molecular mimicry between the a pathogen and the origin of the disease; 3) cross reacting antibodies between the pathogen and self molecules; 4) endothelial cell activation in the 'crime-area' i.e., the valves; 5) some of the patients with RF have circulating antiphospholipid antibodies, while APS may be associated with streptococcal infection; and 6) recently, a cross-reactivity between antibodies directed to the streptococcal M-protein and its synthetic derivative in rheumatic fever (RF) and antibodies derived from APS patients targeting the beta-2-glycoprotein-I (beta2GPI) and a beta2GPI related synthetic peptide. In the current paper, we summarize the possible links between the heart involvement in RF and APS.

Antiphospholipid Syndrome↗
PubMed2005

Oxidized LDL/beta2-glycoprotein I complexes: new aspects in atherosclerosis.

beta2-glycoprotein I (beta2GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with beta2GPI and immunoreactive lymphocytes. oxLDL/beta2GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/beta2GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/beta2GPI complexes were internalized by macrophages via IgG anti-beta2GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.

Anticoagulants↗
PubMed2005

Evaluation of the BioPlex 2200 ANA screen: analysis of 510 healthy subjects: incidence of natural/predictive autoantibodies.

The BioPlex 2200 ANA Screen is a fully automated system that determines levels for 13 different autoimmune antibodies of established clinical significance. The objective of this study was to determine the specificity of the BioPlex 2200 ANA Screen assay and to analyze the antibody profile samples collected from healthy subjects against comparative ELISA and IIF screening methods. A total of 510 specimens were randomly selected from a cohort of apparently healthy blood bank donors. Samples were distributed to five age brackets. All samples were tested using Bio-Rad's ANA Screen kit. Specificity was compared to IIF and ELISA results. Most of the samples were found negative in all ANA screening systems (84.5% by IIF, 92.5% by BioPlex 2200 ANA Screen kit, and 94.5% by ELISA). The frequency of positive results was highest (15.5%) using IIF, in comparison to almost similar results (5.5% vs. 7.5%) achieved by ANA ELISA and BioPlex 2200 ANA Screen kits. The positive rate of autoantibodies was significantly reduced when analyzed by different combinations of ANA screen assays (from 2.35% using IIF + BioPlex ANA Screen tests to 0.98% by using all three tests). Using the BioPlex 2200 ANA Screen system, we were able to identify samples with high levels of individual antibodies: anti-dsDNA at 20-63 IU/mL, antichromatin at 4-8 AI, anti-SmRNP at 2-6 AI, and anti-RNPA at 2-4.5 AI. Importantly, from 7 IIF and ELISA positive sera, 5 of these were also BioPlex 2200 positive, suggesting that the BioPlex is seeing the samples that are of the greatest interest, using the established techniques. The specificity of the BioPlex 2200 ANA Screen analysis of 13 different analytes (dsDNA, centromere B, chromatin, Jo1, ribosomal P, RNP 68, RNP A, Scl-70, Sm, SmPNP, SS-A52, SS-A60, SS-B) is comparable (P < 0.252) to the ELISA ANA screening test. Like the ELISA, the BioPlex 2200 has a lower (P < 0.001) positive rate than IIF for the autoantibody screening.

Age Distribution↗
PubMed2004

Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection.

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.

Antibodies, Anticardiolipin↗
PubMed2004

Antiphospholipid syndrome infectious origin.

Antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against beta 2-glycoprotein-I (beta 2GPI). The factors causing production of anti-beta 2GPI remain unidentified, but an association with infectious agents has been reported. Studies on experimental APS models proved that molecular mimicry between beta 2GPI-related synthetic peptides and structures within bacteria, viruses, tetanus toxoid, and CMV are a cause for experimental APS. Any explanation of how microbial infections might set off APS must take into account the observation that all individuals appear to harbor potentially autoreactive lymphocytes, as well as natural antiphospholipid antibodies, but that these cells or antibodies remain innocuous unless somehow activated. Herein, we discuss the association of antiphospholipid antibodies in the infectious state, molecular mimicry as a proposed cause for development of APS, and the contribution of the database to this topic.

Animals↗
PubMed2004

The systemic nature of the antiphospholipid syndrome.

Antiphospholipid syndrome (APS, Hughes' syndrome) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis and recurrent foetal loss, accompanied by mild to moderate thrombocytopaenia and elevated titres of antiphospholipid antibodies (aPLs): lupus anticoagulant (LAC) and/or anticardiolipin (aCL) antibodies. APS was defined originally in 1983 in systemic lupus erythematosus (SLE) patients, but later it was found that APS can be primary or secondary to other autoimmune diseases or malignancy. During the past 20 years many organs have been reported to be involved in this syndrome and the clinical manifestations are seen in every medical field. Moreover, many aPLs have been found in APS besides aCLs and LACs, which bind to the autoantigen beta-2-glycoprotein I (beta2GPI). Treatment for APS, based on antiplatelet and anticoagulation drugs, is dependent on various parameters, including whether SLE is also present, classical vs non-classical manifestations of the diseases, women with APS based on pregnancy morbidity, the presence of elevated aCL antibody titres in the absence of clinical manifestations, and catastrophic APS.

Antibodies, Anticardiolipin↗
PubMed2004

Evaluation of Bacillus anthracis extractable antigen for testing anthrax immunity.

Three extractable Bacillus anthracis cell-wall-associated antigens were evaluated for potential use as skin testing agents, and as possible candidates for in-vitro diagnosis of anthrax immunity. Anthraxin and a partially purified extractable antigen (EAP) were produced from avirulent B. anthracis strain 34F2 (Sterne). The thermoextractable antigen used for the Ascoli reaction was obtained commercially. Guinea-pigs were immunised and boosted several times subcutaneously with the Sterne live veterinary anthrax vaccine. Four weeks after the last booster dose, animals were skin-tested with the three antigens. Serum antibody levels were also determined by ELISA, and the in-vitro T-cell response was evaluated by [3H]-thymidine incorporation. EAP was the most active antigen in both the serological and cellular reactions. EAP also elicited a distinct positive skin reaction in animals immunised with B. anthracis. The data obtained in this preliminary study indicated that extractable cell-wall antigens obtained from the vegetative form of B. anthracis may be used for skin tests and in-vitro testing of specific humoral and cell-mediated anthrax immunity.

Animals↗
PubMed2004

Autoantibody panel screening in recurrent miscarriages.

PROBLEM: Antiphospholipid autoantibodies (aPL), antithyroid antibodies and anti-extractable nuclear antigens (anti-ENA) have all been reported to be associated with recurrent miscarriages (RM) and infertility. However, this association remained controversial. MATERIALS AND METHODS: Fifty-eight women with impaired fertility (38 women with RM and 20 women with infertility, but no miscarriages) and 28 control parous women were screened for seven autoantibodies [antithyroglobulin (aTG), antithyroid peroxidase (aTPO), anticardiolipin (aCL), antiphosphatidyl-serine (aPS), antiprothrombin antibodies (aPT), anti-beta 2 glycoprotein 1 (abeta2GP1), and anti-ENA]. There was no evidence for autoimmune diseases in the patients or the control. The analysis was also performed with several panels of autoantibodies, each of which contained two or more autoantibodies. RESULTS: Anti-TPO was the only antibody to be associated with RM (P = 0.01). A significant association was found between RM, and autoantibodies in the 'aTG + aTPO + anti-ENA' or 'aTG + aTPO' panels. The 'aTG + aTPO + anti-ENA' panel was also associated with RM when the analysis was performed only on 17 women who had secondary infertility: 10 from the 38 women with RM, and seven from the 20 women with infertility and no miscarriages. A significant association (P < 0.001) was also apparent between anti-CL and anti-PS and infertility compared with the 28 control women. CONCLUSIONS: RM was associated with autoantibodies to aTPO and the combined panel of aTPO, aTG and anti-ENA, but not with aPL. aPL were associated with infertility.

Abortion, Habitual↗
PubMed2004

Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity.

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. OBJECTIVE: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. METHODS: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age </=59 years), with DAS28 </=3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls. RESULTS: Mean (SD) FMV was significantly lower in patients than in controls (3.2 (1.3)% v 5.7 (2.0)%; p<0.001), inversely related to low density lipoprotein cholesterol (r = -0.45, p<0.05) and C reactive protein (CRP), expressed as the value at the moment of ultrasound evaluation (r = -0.44, p<0.05), as the average of CRP levels evaluated at different times during the disease (r = -0.47, p<0.05), or as the average of >/=4 determinations multiplied by the disease duration (r = -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta = -0.28, p<0.05). CONCLUSIONS: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.

Adult↗
PubMed2004

IgA and IgG tissue transglutaminase antibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) and coeliac disease (CD) are diseases of an autoimmune origin that share the human leukocyte HLA-B8 and HLA-DR3 histocompatibility antigens, yet the co-association of CD with SLE is mainly based on case reports. Thus, the real prevalence of CD in SLE is unclear. The aim of this study was to determine the prevalence of antitissue transglutaminase (anti-tTG) in SLE and the relation between SLE and CD. In this case-control study, 100 patients with SLE, and 120 healthy subjects were studied. Sera from all participants were analysed for the presence of IgA and IgG anti-tTG antibodies using a human recombinant tissue transglutaminase (tTG) immuno-enzymatic assay. Anti-tTG positive patients and controls were further tested for antiendomysial (EMA) antibodies by an indirect immunofluorescence and HLA typing (DQalpha1*0501-DQbeta1*0201 allele determination). Subjects who had EMA or the mentioned allele, underwent duodenal biopsy to confirm a possible diagnosis of CD. Anti-tTG antibodies (IgA or IgG isotypes) were found in three of the 100 SLE patients (overall prevalence of 3%): one had the IgA and two the IgG isotypes. Only 1 of 120 healthy subjects (0.8%) had a low positive reaction for IgA anti-tTG. Only the IgA anti-tTG positive SLE patient was diagnosed as having CD based on a positive IgA-EMA and small bowel biopsy findings. The two IgG anti-tTG positive SLE patients and the IgA anti-tTG positive healthy subject were classified as false positives (EMA negative and HLA DQalpha1*0501-DQbeta1*0201 allele negative). In conclusion, anti-tTG antibodies were found at a low rate in SLE patients and mostly did not indicate the presence of CD. Thus, serological screening for CD is not recommended in SLE, unless a clinical suspicion of CD is present.

Adolescent↗