Zabludowicz Center for Autoimmune Diseases

Tel Aviv, Israel

Zabludowicz Center for Autoimmune Diseases

Tel Aviv, Israel
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Guimaraes L.E.,Zabludowicz Center for Autoimmune Diseases | Baker B.,Zabludowicz Center for Autoimmune Diseases | Perricone C.,University of Rome La Sapienza | Shoenfeld Y.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University
Pharmacological Research | Year: 2015

Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. © 2015 Elsevier Ltd. All rights reserved.

Shapira Y.,Zabludowicz Center for Autoimmune Diseases | Agmon-Levin N.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Center for Autoimmune Diseases
Nature Reviews Rheumatology | Year: 2010

The accumulative global burden of autoimmune and inflammatory rheumatic diseases is substantial. Studying the distribution of these conditions across various global regions and ethnic groups by means of geoepidemiology might readily provide epidemiological data and also advance our understanding of their genetic and environmental underpinnings. In order to depict the geoepidemiology of autoimmune and inflammatory rheumatic diseases, namely rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, ankylosing spondylitis and Sjögren's syndrome, we present a comprehensive collection of epidemiological reports from various world regions, including the prevalence of each of these conditions. The accumulated data show that the reviewed rheumatic diseases are global phenomena, and, with some variance, seem to be relatively evenly distributed. This finding is in contrast with the obviously uneven distribution of some major nonrheumatic autoimmune conditions. In addition, geoepidemiology demonstrates that ethnogenetic susceptibility interacts with lifestyle and environmental factors, which include socioeconomic status, infectious agents (triggering or protective agents), environmental pollutants, and vitamin D (dependent on sunlight exposure), in determining the risk of developing rheumatic autoimmunity. © 2010 Macmillan Publishers Limited.

Ehrenfeld M.,Zabludowicz Center for Autoimmune Diseases | Ehrenfeld M.,Rheumatic Disease Unit | Ehrenfeld M.,Tel Aviv University
Best Practice and Research: Clinical Rheumatology | Year: 2012

Spondyloarthropathies (SpA) are a group of common inflammatory rheumatic disorders characterised by axial and or peripheral arthritis, associated with enthesitis, dactylitis and potential extra-articular manifestations such as uveitis and skin rash. The diseases, which comprise the group, share a common genetic predisposition, the HLA-B27 gene; however, this association varies markedly among the various SpAs and among different ethnic groups. Environmental factors seem to be triggering the diseases in the genetically predisposed individuals. The radiographic hallmark of the group is sacroiliitis, which when present is of help in the diagnosis. Various sets of diagnostic and classification criteria were developed over the years including the European Spondyloarthropathy Study Group (ESSG) criteria which were until recently the most widely used. The new Assessment in SpondyloArthritis international Society (ASAS) international working group has recently proposed a new set of diagnostic criteria that would enable identification of SpA before structural changes develop in the spine. Magnetic resonance imaging (MRI) changes have now been included in the new classification criteria of early axial SpA and are now considered as a major tool in the diagnosis. Until recently, there were no real disease-modifying anti-rheumatic drugs which were able to halt the disease progression. Over the past decade, tumour necrosis factor (TNF)-alfa-blocking agents have been extensively investigated and became the mainstream of therapy providing the patients an effective treatment option. © 2012 Elsevier Ltd. All rights reserved.

Rosman Z.,Wolfson Medical Center | Shoenfeld Y.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University | Zandman-Goddard G.,Wolfson Medical Center | Zandman-Goddard G.,Tel Aviv University
BMC Medicine | Year: 2013

Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis. © 2013 Rosman et al.; licensee BioMed Central Ltd.

Drori T.,Tel Aviv University | Chapman J.,Tel Aviv University | Chapman J.,Zabludowicz Center for Autoimmune diseases
Autoimmunity Reviews | Year: 2014

Neuromyelitis optica (NMO) is an autoimmune disorder, predominantly characterized by severe optic neuritis (ON) and transverse myelitis (TM). Historically considered a variant of Multiple sclerosis, the discovery that most NMO patients have autoantibodies against aquaporin-4 (AQP4) or NMO-IgG, dramatically changed our understanding of the disease. The finding of NMO-IgG revealed wider array of clinical presentations, including patients with recurrent ON of TM alone, now considered part of the NMO spectrum. Furthermore, symptoms other than optic-spinal involvement and the presence of brain lesions, do not exclude the diagnosis of NMO as traditionally accepted. We present an overview of the epidemiology, clinical manifestations and current diagnostic criteria for NMO and NMO spectrum disorders. © 2014 Elsevier B.V.

Mazor R.D.,Zabludowicz Center for Autoimmune Diseases | Mazor R.D.,Tel Aviv University | Manevich-Mazor M.,Tel Aviv University | Shoenfeld Y.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University
Orphanet Journal of Rare Diseases | Year: 2013

Erdheim-Chester Disease (ECD) is a rare form of non Langerhans' cell histiocytosis. Individuals affected by this disease are typically adults between their 5th and 7th decades of life. Males and females are almost equally affected. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. The etiology of ECD is unknown yet thought to be associated with an intense TH1 immune response. It may also be associated with the V600E BRAF mutation, as described in as many as half of the patients in recent studies. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(-) histiocytes are identified within a biopsy specimen. At present, this obscure ailment embodies numerous challenges to medical science. Given its rarity, it is diagnostically elusive and requires a high level of clinical suspicion. Therapeutically, it is of limited alternatives. Currently, interferon is the most extensively studied agent in the treatment of ECD and serves as the first line of treatment. Treatment with other agents is based on anecdotal case reports and on the basis of biological rationale. Nevertheless, cladribine (2CDA), anakinra and vemurafenib are currently advocated as promising second line treatments for patients whose response to interferon is unsatisfactory. Overall, the 5 year survival of ECD is 68%. Herein, the authors mustered and brought about a panoramic consolidation of all the relevant facts regarding ECD. This work highlights the different clinical, radiological and pathological manifestations associated with ECD, the differential diagnoses, the various treatment options and the acknowledged science explaining the disease. © 2013 Mazor et al.; licensee BioMed Central Ltd.

Hersalis Eldar A.,Sheba Medical Center | Chapman J.,Sheba Medical Center | Chapman J.,Zabludowicz Center for Autoimmune Diseases
Autoimmunity Reviews | Year: 2014

Immune mediated neuropathies are uncommon but important to diagnose because they are potentially treatable. This chapter summarizes the clinical approach to diagnosis of Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and related neuropathies which are thought to be caused by direct autoimmune attack on peripheral nerves. © 2014 Elsevier B.V.

Ortega-Hernandez O.-D.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Zabludowicz Center for Autoimmune Diseases
Best Practice and Research: Clinical Rheumatology | Year: 2012

The most common clinical manifestations of mixed connective disease are Raynaud's phenomenon, arthralgias, swollen joints, esophageal dysfunction, muscle weakness and fingers sausage-like appearance together with the presence of anti-ribonucleoprotein (RNP) antibodies. However, organ involvement is more extensive than first descriptions reported. The disease can be serious with development of pulmonary, kidney, cardiovascular, gastrointestinal and central nervous system manifestations. The worst prognosis and high mortality are associated with the presence of pulmonary disease. Although a different set of clinical criteria have been proposed, there is no consensus about the most accurate. There is no full agreement about treatment and the initial impression of a satisfactory response to low doses of steroids is not always the rule. Herein, we review available evidence to a better approach to all previous topics. © 2012 Elsevier Ltd. All rights reserved.

Ben-Zvi I.,Zabludowicz Center for Autoimmune Diseases | Kivity S.,Zabludowicz Center for Autoimmune Diseases | Langevitz P.,Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Zabludowicz Center for Autoimmune Diseases
Clinical Reviews in Allergy and Immunology | Year: 2012

Quinine was first recognized as a potent antimalarial agent hundreds of years ago. Since then, the beneficial effects of quinine and its more advanced synthetic forms, chloroquine and hydroxychloroquine, have been increasingly recognized in a myriad of other diseases in addition to malaria. In recent years, antimalarials were shown to have various immunomodulatory effects, and currently have an established role in the management of rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, skin diseases, and in the treatment of chronic Q fever. Lately, additional metabolic, cardiovascular, antithrombotic, and antineoplastic effects of antimalarials were shown. In this review, we discuss the known various immunomodulatory mechanisms of antimalarials and the current evidence for their beneficial effects in various diseases and in potential novel applications. © 2011 Springer Science+Business Media, LLC.

Israeli E.,Zabludowicz Center for Autoimmune Diseases
Lupus | Year: 2012

Gulf War syndrome (GWS) is a multi-symptom condition comprising a variety of signs and symptoms described in the literature, which not been fully resolved. The various symptoms of the condition include muscle fatigue and tiredness, malaise, myalgia, impaired cognition, ataxia, diarrhoea, bladder dysfunction, sweating disturbances, headaches, fever, arthralgia, skin rashes, and gastrointestinal and sleep disturbances. In addition, excessive chemical sensitivity and odour intolerance is reported. The aetiology of the condition is unclear, but many reviews and epidemiological analyses suggest association with pyridostigmine bromide (PB), certain vaccination regimes, a variety of possible chemical exposures, including smoke from oil-well fires or depleted uranium from shells, as well as physical and psychological stress. Recently, Shoenfeld et al. suggested that four conditions-siliconosis, macrophagic myofaciitis (MMF), GWS and post-vaccination phenomena-that share clinical and pathogenic resemblances, may be incorporated into common syndrome called 'Autoimmune (Autoinflammatory) Syndrome induced by Adjuvants' (ASIA). Symptoms and signs of the four conditions described by Shoenfeld et al. show that at least eight out of ten main symptoms are in correlation in all four conditions. Namely, myalgia, arthralgias, chronic fatigue, neurological cognitive impairment, gastrointestinal symptoms, respiratory symptoms, skin manifestations and appearance of autoantibodies. Regardless of the aetiology of GWS, be it exposure to environmental factors or chemical drugs, vaccinations or the adjuvants in them, GWS fits well with the definition of ASIA and is included as part of 'Shoenfeld's syndrome'. © The Author(s), 2012.

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