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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 19 recordsLinked to original sources
PubMed2007

Protective autoimmunity in cancer (review).

Not all malignant cells progress to invasive cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are complex and provide continuous efforts for the removal of transformed cells. Naturally occurring antibodies are frontier soldiers that act as the first line of defense in the battle against cancer. During the process of carcinogenesis naturally occurring antibody responses to tumor antigens were found to be associated with improved survival and protection against the spread of cancer. Using the human hybridoma technology, a series of tumor-binding antibodies can be isolated as they have several common features: they are germ-line coded IgM antibodies, they bind to various tumor-antigens, they induce apoptosis of malignant cells, and most importantly they detect not only malignant cells but also the precursor stages (i.e., autoantigens). Natural protective autoantibodies against tumor-antigens were isolated from patients and healthy donors reflecting the development of naturally occurring B-cell responses during the process of cancer evolvement. They fulfill the definition of autoantibodies since they are self-reactive and they also bind altered self-antigens such as tumor cells. In this regard various autoantibodies such as anti-dsDNA and anti-Fas autoantibodies were found to be significantly higher in patients with various carcinomas, thus playing a role for their improved survival. Targeting T-regulatory cells, namely the expression of CTLA-4 was also found to improve survival in cancer patients. Autoimmunity and malignancy frequently coexist and they may share etiological and pathological mechanisms. Therefore, the efficacy of intravenous immunoglobulins or CTLA-4 blockade was also employed as a treatment for prevention of malignancy and metastases spread.

Antigens, CD↗
PubMed2006

Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: association with autoimmunity.

In this study we aimed to determine whether serum B-lymphocyte activating factor (BAFF) level is increased in patients with chronic hepatitis C virus (HCV) infection, and to assess its association with HCV-related autoimmunity. Sixty-five patients with chronic HCV infection were compared with two disease control groups [57 patients with systemic lupus erythematosus (SLE) and 15 with chronic hepatitis B virus (HBV) infection] and a healthy control group of 35 individuals. A special attention was given to HCV-related arthralgia and or vasculitis. Serum BAFF was assessed in all studied individuals, whereas rheumatoid factor (RF), anti-cardiolipin antibodies (aCL), and cryoglobulins were determined in HCV and HBV infected patients, and anti-dsDNA antibodies and aCL were assessed in patients with SLE. Mean serum BAFF was increased in patients with HCV infection and SLE (2.4+/-0.8 ng/ml and 3.1+/-1.34 ng/ml respectively) compared to 1.1+/-0.14 ng/ml in patients with HBV; and to 1.1+/-0.27 in healthy controls (all, p<0.0001). The elevation in serum BAFF was associated with HCV-related arthralgia and or vasculitis (p<0.0001), and with the presence of aCL and of cryoglobulins. HBV patients lacked features suggestive of autoimmunity. In SLE patients, elevated serum BAFF was in association with the presence of anti-dsDNA (p=0.002). As in other autoimmune diseases, increased serum BAFF was also found in patients with chronic HCV infection. Elevated serum BAFF levels were associated with clinical and laboratory features of autoimmunity, suggesting that BAFF may play a role in HCV-related autoimmunity.

Adult↗
PubMed2006

The catastrophic antiphospholipid (Asherson's) syndrome and malignancies.

The catastrophic antiphospholipid syndrome is characterised by the rapid chronological development of fulminant thrombotic complications that predominantly affect small vessels. It has been reported as frequently occurring in patients with underlying malignancies. We analysed the web site-based international registry of patients with catastrophic APS. The clinical characteristics of patients with CAPS and an underlying malignancy were evaluated. Of the 262 patients included in the CAPS registry, information on associated malignancies was available in 23 (9%) cases. Haematological malignancies were present in 6 (26%) patients. Four of the patients suffered from lung carcinoma (17%), and two patients (9%) from colon carcinoma. In most of the patients (61%), malignancy was the precipitating factor for CAPS. In 4 patients (17%), however, surgical procedures related to the carcinoma were noted as precipitating factors. In one patient CAPS occurred during allogenic stem cell transplantation after diagnosis of acute lymphoblastic leukemia (ALL). Cerebral manifestations were most common and consisted mainly of cerebral infarcts and encephalopathy. Recovery occurred in 9/23 (39%) patients. Malignancy may be an important risk factor for CAPS. 9% of patients with CAPS presented with an underlying malignancy. In most of these patients, the malignancy and/or surgical procedures were the precipitating factors for CAPS.

Adolescent↗
PubMed2006

Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome.

OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions. METHODS: Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea. CONCLUSIONS: The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.

Acetylglucosamine↗
PubMed2006

The autoimmune characteristics of progressive or sudden sensorineural hearing loss.

Autoimmune sensorineural hearing loss (ASNHL) is a clinical syndrome that typically produces a bilateral rapidly progressive hearing loss. Autoantibodies and autoreactive T cells have been implicated in the etiopathogenesis of ASNHL. However, the identity of a specific or highly relevant inner-ear self-antigen is still required. In recent years, a role for antiphospholipid antibodies has been also suggested, assuming sudden/progressive hearing loss to be part of the primary antiphospholipid syndrome (APS). In this review, we address the need for specific diagnostic tools in order to establish an autoimmune origin for hearing loss. Moreover, the decision of whether anti-inflammatory drugs or anti-coagulation should be given is also discussed.

Antiphospholipid Syndrome↗
PubMed2006

Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and neonatal lupus.

Cardiac involvement is one of the main complications substantially contributing to the morbidity and mortality of patients suffering from systemic autoimmune diseases. All the anatomical heart structures can be affected, and multiple pathogenic mechanisms have been reported. Non-organ-specific autoantibodies have been implicated in immune complex formation and deposition as the initial triggers for inflammatory processes responsible for Libman-Sacks verrucous endocarditis, myocarditis and pericarditis. Anti-phospholipid antibodies have been associated with thrombotic events in coronary arteries, heart valve involvement and intra-myocardial vasculopathy in the context of primary and secondary anti-phospholipid syndrome. Antibodies-SSA/Ro and anti-SSB/La antigens play a major pathogenic role in affecting the heart conduction tissue leading to the electrocardiographic abnormalities of the neonatal lupus syndrome and have been closely associated with endocardial fibroelastosis.

Antibodies, Antiphospholipid↗
PubMed2006

The reduction of serum B-lymphocyte activating factor levels following quinacrine add-on therapy in systemic lupus erythematosus.

B-Lymphocyte-activating factor (BAFF/BLyS) is a survival factor for B cells, belonging to the tumor necrosis ligand super family. Serum BAFF levels have been found to be elevated in patients with systemic lupus erythematosus (SLE). Neutralization of BAFF activity was suggested as an additional therapeutic approach in SLE. To determine the effect of add-on Quinacrine (Qn) treatment on serum BAFF levels and the effect of this treatment on SLE disease activity index (SLEDAI), antidsDNA and anticardiolipin (aCL) antibody levels, we treated 29 stable SLE patients, who were maintained on prednisolone and hydroxychloroquine and in some on azathioprine (AZT), with additional Qn (100 mg/d) with an aim to further reduce disease activity. SLEDAI, antidsDNA, aCL antibodies and serum BAFF levels were assessed before and 3 months after the addition of Qn. Three months following Qn initiation, a reduction in SLEDAI was noticed in 19/29 patients (mean 8.8 +/- 2.3 to 3.3 +/- 1.5, P = 0.009), followed by reduction or discontinuation of prednisolone in all patients and the discontinuation of AZT in five patients. Serum BAFF levels were significantly reduced in 8/12 patients (mean 6.3 +/- 0.5 to 3.0 +/- 0.56 ng/ml P = 0.0001). This reduction was found in correlation with a decrease in aCL titres. However, the decrease in SLEDAI scores and antidsDNA antibody titres was unrelated to the decrease in serum BAFF or aCL levels. We conclude that the addition of Qn to previous therapeutic regimens in active SLE is beneficial and seems to reduce SLEDAI scores, serum BAFF and aCL levels and therefore should be considered in many of our SLE patients before aggressive treatments are given.

Adult↗
PubMed2006

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).

New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.

Antibodies, Antiphospholipid↗
PubMed2006

The environment and antiphospholipid syndrome.

The etiology of autoimmune diseases is multifactorial. The degree to which genetic and environmental factors influence susceptibility to autoimmune diseases is poorly defined. It is believed that versatile clinical presentations of autoimmune diseases stem from various combinations of the genetic and environmental factors. One of the newly diagnosed autoimmune diseases is the antiphospholipid syndrome (APS). APS is characterized by vascular thrombosis, and/or pregnancy morbidity associated with anticardiolipin (aCL), anti-beta2-glycoprotein-I (anti-beta2GPI) and lupus anticoagulant (LAC).

Antibodies, Antiphospholipid↗
PubMed2006

Epilepsy as part of systemic lupus erythematosus and systemic antiphospholipid syndrome (Hughes syndrome).

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPL), demonstrated by ELISAs for antibodies against phospholipids and associated phospholipid-binding cofactor proteins and/or a circulating lupus anticoagulant (LA) together with diverse systemic clinical manifestations such as thrombosis, and recurrent spontaneous abortions. According to the criteria set out in Sydney the only neurological manifestations that can be suitable as APS classification criteria are ischemic events (stroke and transient ischemic attacks). However, other neurological manifestations, including seizures in particular, have been repeatedly reported in APS patients. The present review will summarize recent research on the association of aPL, as well as other autoantibodies, with seizure disorders, with or without concomitant SLE.

Antibodies, Antiphospholipid↗
PubMed2006

Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity.

Autoimmune connective tissue diseases are chronic, potentially life threatening complex multisystem disorders. Their etiology is unknown but genetic, hormonal and environmental factors are important. The clinical disease is preceded by a long period of time (sometimes many years) when the patients can be identified by characteristic antibodies in their serum. When such a patient is identified he is usually followed and treated if clinical disease manifests itself. However, other factors besides the existence of autoantibodies have a predictive value for those disorders; some of them hereditary or genetic, and can be used only to predict likelihood of future disease, and others, connected to lifestyle and environment, could be modified in order to try and prevent it. Several non-randomized small scale studies have suggested that autoimmune disease could be prevented if treated aggressively prior to manifestations of symptoms. However, if such is the case, criteria would have to be formalized for selection of patients for this preventive treatment. Only patients whose probability to develop clinical disease is higher then a certain threshold should be treated while asymptomatic. The aim of this article is to review the major risk factors for autoimmune disease, both hereditary and environmental, and so to help define those future criteria. Individuals who are at risk to develop an autoimmune disease should be advised to refrain from activities and lifestyle which endangers their health and quality of life.

Autoantibodies↗
PubMed2006

The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans.

Although multiple studies suggest a potential role for angiotensin II in inflammation, most were performed either in vitro or in animals with non-immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice, angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than cyclophosphamide and diminished the glomerular histopathologic damage, proteinuria, lymphoid hyperplasia, dermatitis, and hypergammaglobulinemia, with a reduction in TGF-beta1 and beta 2 expression in the kidneys and renal chemokine mRNA expression. Spleen levels of IL-4 and IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory lupus nephritis showed a significant reduction in proteinuria with ACE-inhibitors and Angiotensin receptor blockers treatment. The 'masking' effect of ACE-inhibitors should be taken into consideration, as an exacerbation of lupus nephritis may be missed when estimated by the magnitude of proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses, ACE-inhibitor use predicted a favourable outcome in 94 cases of pauci-immune vasculitis. The attenuating effect of angiotensin II inhibitors on the progression of chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.

Angiotensin II↗
PubMed2006

European attempts to set guidelines for improving diagnostics of autoimmune rheumatic disorders.

The rational way to set a diagnosis and estimate a prognosis in rheumatology is to start by setting a tentative diagnosis and then follow a fixed scheme for laboratory testing, eg, by using an agreed algorithm. The use of order algorithms can be extended to post-test algorithms that will assist clinicians in approaching the right diagnosis and prognosis. New methods used in autoimmune serology do not deliver results that can be directly compared to those of older methods, and thus the new methods need to be thoroughly tested with sera from differential diagnostically relevant disease controls to set a clinically meaningful cut-off for positivity. Borderline positive results need to be treated with special care to avoid misuse. Early diagnosis is of great importance, and serological results can be very useful if used the right way. European efforts to secure rational diagnostic work-up in autoimmune rheumatic disease have led to a better dialogue between clinicians and laboratory scientists in several countries.

Algorithms↗
PubMed2006

Application of a static fluorescence-based cytometer: the CellScan in clinical immunology.

The CellScan system is a laser scanning cytometer which enables repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. By monitoring FP changes in peripheral blood lymphocytes (PBL) following exposure to antigenic stimuli, the CellScan may have a role in the diagnosis of autoimmune diseases. Monitoring changes in FI and FP in PBLs from patients with atherosclerosis following exposure to various stimuli, has illustrated the role of the immune system in the atherosclerotic process. The CellScan has also been evaluated as a diagnostic tool for drug-induced allergy, based on FP reduction in PBLs following incubation with the suspected drugs. FI and FP changes in cancer cells have been found to correlate with the cytotoxic effect of different anti-neoplastic drugs, illustrating the potential role of the CellScan system in clinical oncology. In conclusion, the CellScan is a promising new tool with a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.

Atherosclerosis↗
PubMed2006

Stenosis in antiphospholipid syndrome: a new finding with clinical implications.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a variety of clinical manifestations. Recent studies suggest arterial stenosis is involved in APS. Furthermore, arterial stenosis may be a relevant and treatable cause for hypertension, renal, CNS and gastrointestinal manifestations of APS. Our objective was to overview the published data regarding arterial stenosis in APS--the clinical presentation, diagnosis, suggested therapies and the possible mechanisms. We searched PUBMED (1951-2006) reference lists for the role of arterial stenosis in APS. APS patients might present with arterial stenosis. Its recognition has important diagnostic and therapeutic implications. Articles suggest that anticoagulation treatment with INR above three may reverse the artery stenosis and achieve subsequent clinical improvement. Currently, there are no specific guidelines for the management of APS patients with arterial stenosis. The exact mechanism of arterial stenosis in APS patients remains unclear.

Antiphospholipid Syndrome↗
PubMed2006

Autoimmune hemolytic anaemia in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a multisystem disease with recurrent thrombosis in the presence of antiphosphlipid antibodies, which may include cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations. The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well established. The purpose of this study was to review the occurrence of AIHA in patients with APS and its relation to other disease manifestations. Three-hundred and eight patients with APS from seven medical centers in Israel, Serbia and the Slovac Republic were included and evaluated for associations between AIHA and various manifestations of APS. AIHA was documented in 32 patients (10.4%). The odds ration for AIHA was increased in the presence of anticardiolipin antibodies and livedo reticularis (5.4 and 7.8, respectively). There was a highly significant association between AIHA and cardiac valvular vegetations and thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P < 0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03, respectively). Thus, APS patients with AIHA are at risk of developing these manifestations, and should therefore be investigated for them. In addition, the occurrence of AIHA may define a subgroup of patients with a significant risk for subsequent development of SLE.

Adult↗