The Zabludowicz Center for Autoimmune Diseases

Tel Aviv, Israel

The Zabludowicz Center for Autoimmune Diseases

Tel Aviv, Israel
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Bogdanos D.P.,King's College London | Bogdanos D.P.,University of Thessaly | Smyk D.S.,King's College London | Invernizzi P.,Center for Autoimmune Liver Diseases | And 4 more authors.
Autoimmunity Reviews | Year: 2013

The "exposome" is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the "infectome", which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the "immunome" and "microbiome" projects. © 2012 Elsevier B.V.


Perricone C.,The Zabludowicz Center for Autoimmune Diseases | Perricone C.,University of Rome La Sapienza | Colafrancesco S.,The Zabludowicz Center for Autoimmune Diseases | Colafrancesco S.,University of Rome La Sapienza | And 6 more authors.
Journal of Autoimmunity | Year: 2013

In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance. © 2013.


Damoiseaux J.,Maastricht University | Andrade L.E.,University of Sao Paulo | Andrade L.E.,Fleury Medicine and Health Laboratories | Fritzler M.J.,University of Calgary | Shoenfeld Y.,The Zabludowicz Center for Autoimmune Diseases
Autoimmunity Reviews | Year: 2015

At the 12th International Workshop on Autoantibodies and Autoimmunity (IWAA), organized in August 2014 in Sao Paulo, Brazil, more than 300 autoimmunologists gathered to discuss the status of many novel autoantibodies in clinical practice, and to envisage additional value of autoantibodies in terms of prediction, prognosis and prevention of autoimmune diseases. Two separate workshops were dedicated to standardization and harmonization of autoantibody testing and nomenclature: International Autoantibody Standardization (IAS) and International Consensus on ANA Patterns (ICAP). It was apparent to all in attendance that the discovery and elucidation of novel autoantibodies did not slow down, but that multiple challenges lay ahead of us in order to apply these discoveries to effective and efficient clinical practice. Importantly, this requires optimal bidirectional communication between clinicians and laboratory specialists, as well as close collaboration with the diagnostic industry. This paper is a report on the 12th IWAA in combination with a review of the recent developments in the field of autoantibodies. © 2015 Elsevier B.V.


Versini M.,The Zabludowicz Center for Autoimmune Diseases | Versini M.,University of Nice Sophia Antipolis | Jeandel P.-Y.,University of Nice Sophia Antipolis | Rosenthal E.,University of Nice Sophia Antipolis | And 2 more authors.
Autoimmunity Reviews | Year: 2014

In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR. =. 1.2-3.4), MS (OR. =. 2), psoriasis and PsA (OR. =. 1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases. © 2014 Elsevier B.V.


Bizzaro G.,The Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,The Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University
Immunologic Research | Year: 2014

Vitamin D deficiency (levels lower than 20 ng/ml) is becoming a global health problem, since it is increasingly represented even among healthy subjects. Vitamin D, as an environmental factor, is involved in many biological processes, like perception of chronic pain and response to infections. In recent years, evidence has emerged pointing to an involvement of vitamin D in the development of many autoimmune diseases, and a severe vitamin D deficiency has been especially demonstrated in patients affected with autoimmune thyroid disease (AITD). Low levels of vitamin D were found associated with antithyroid antibody presence, abnormal thyroid function, increased thyroid volume, increased TSH levels, and adverse pregnancy outcome in women with AITD. Vitamin D mediates its effect through binding to vitamin D receptor (VDR), which is harbored on many human immune cells, and in this way is able to modulate immune cells activity, triggering both innate and adaptive immune responses. As VDR gene polymorphisms were found to associate with AITD, the evidence links vitamin D deficiency to AITD either through gene polymorphism or by environmental factors (lack of dietary uptake and sun exposure). Vitamin D supplementation may be offered to AITD patients, but further research is needed to define whether it should be introduced in clinical practice. © 2014, Springer Science+Business Media New York.


Nussinovitch U.,Israel Defense Forces | Shoenfeld Y.,The Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University
Autoimmunity Reviews | Year: 2012

Autoimmunity is influenced by multiple factors including gender and sex hormones. A definite female predominance is found in many autoimmune diseases. Gender is also associated with differences in clinical presentation, onset, progression and outcome of autoimmune diseases. Sex hormones might influence the target organ's vulnerability to an autoimmune response. Gender differences also exist in organ specific autoimmune diseases such as multiple sclerosis, Guillain-Barré syndrome, Crohn's disease and celiac disease. Nevertheless, other organ specific autoimmune diseases (i.e. ulcerative colitis) are seemingly characterized with similar prevalence in both males and females. The reason for gender differences in certain autoimmune diseases remains unknown, but may be attributed to sex hormone influence, fetal microchimerism, X chromosome inactivation, and X chromosome abnormalities. Sex hormones have been found to have immune modulating properties, as well as providing cellular protection following tissue damage in certain circumstances. Sex hormones also influence innate and adaptive immune cells, number of B and T cells, antigen presentation and cytokine secretion. Herein, we review the influence of gender on organ-specific autoimmune diseases affecting the heart, blood vessels, central nervous system and gastrointestinal tract. It appears that sex hormones may have a therapeutic potential in several autoimmune conditions, although further research is required before therapeutic recommendations can be made. © 2011 Elsevier B.V.


Valesini G.,University of Rome La Sapienza | Gerardi M.C.,University of Rome La Sapienza | Iannuccelli C.,University of Rome La Sapienza | Pacucci V.A.,University of Rome La Sapienza | And 3 more authors.
Autoimmunity Reviews | Year: 2015

Autoimmune diseases are characterized by the body's own immune system attack to the self-tissues, a condition enabled, in predisposed subjects, by the reduction of self-tolerance. A central role has been recently recognized to post-translational modifications, since they can promote generation of neo-(auto)antigens and in turn an autoimmune response. During the last years great attention has been paid to citrullination, because of its role in inducing anti-citrullinated proteins/peptide antibodies (ACPA), a class of autoantibodies with diagnostic, predictive and prognostic value for Rheumatoid Arthritis (RA). Nonetheless, citrullination has been reported to be a process present in a wide range of inflammatory tissues. Indeed, citrullinated proteins have been detected also in other inflammatory arthritides and in inflammatory conditions other than arthritides (polymyositis, inflammatory bowel disease and chronic tonsillitis). Moreover, environmental exposure to cigarette smoke and nanomaterials of air pollution may be able to induce citrullination in lung cells prior to any detectable onset of inflammatory responses, suggesting that protein citrullination could be considered as a sign of early cellular damage. Accordingly, citrullination seems to be implicated in all those para-physiological processes, such as cells death pathways, in which intracellular calcium concentration raises to higher levels than in physiologic conditions: hence, peptidylarginine deiminases enzymes are activated during apoptosis, autophagy and NETosis, processes which are well-known to be implicated in autoimmunity. Taken together, these data support the hypothesis that rather than being a disease-dependent process, citrullination is an inflammatory-dependent condition that plays a central role in autoimmune diseases. © 2015 Elsevier B.V.


Bashi T.,The Zabludowicz Center for Autoimmune Diseases | Bizzaro G.,The Zabludowicz Center for Autoimmune Diseases | Ben-Ami Shor D.,The Zabludowicz Center for Autoimmune Diseases | Ben-Ami Shor D.,Sheba Medical Center | And 3 more authors.
Autoimmunity Reviews | Year: 2015

The incidence of autoimmune diseases has risen throughout the last half a century, mostly in the industrialized world. Helminths and their derivatives were found to have a protective role in autoimmunity and inflammatory conditions, as they manipulate the immune network, attenuating the host's cellular and humoral responses. Indeed, various helminth species used in several human and animal models were shown to limit inflammatory activity in a variety of diseases including inflammatory bowel disease, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Our review will focus on the main mechanisms by which helminths and their secreted molecules modulate the host's immune system. The main pathways induce a shift from Th1 to Th2 phenotype, accelerate T regulatory and B regulatory phenotypes, and attenuate the levels of the inflammatory cytokines, leading to a tolerable scenario. © 2014 Elsevier B.V.


Shoenfeld Y.,The Zabludowicz Center for Autoimmune Diseases | Shoenfeld Y.,Tel Aviv University | Agmon-Levin N.,The Zabludowicz Center for Autoimmune Diseases
Journal of Autoimmunity | Year: 2011

The role of various environmental factors in the pathogenesis of immune mediated diseases is well established. Of which, factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were associated with defined and non-defined immune mediated diseases both in animal models and in humans. In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, "Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants" © 2010 Elsevier Ltd.


Lerner A.,Technion - Israel Institute of Technology | Blank M.,The Zabludowicz Center for Autoimmune Diseases
Autoimmunity Reviews | Year: 2014

Celiac disease is a life-long autoimmune disease affecting multiple organs of genetically susceptible individuals. One of the extra intestinal manifestations of the disease is thromboembolic events like strokes, veins' thrombosis, and pregnancy losses. Hypercoagulable autoimmune diseases like lupus erythematosus and antiphospholipid syndrome, associated with celiac disease just add risk to the patients. Pathogenic predisposing avenues increasing the hypercoagulability in celiac disease are multiple: nutritional deficiencies (B12, folate, and vitamin K), genetic predisposition (MTHFR mutations), thrombophilic autoantibodies, hyperhomocysinemia, endothelial dysfunction and platelet abnormalities. Primary pharmacologic thromboprophylaxis or treating the predisposing factors should be considered on a personal basis. © 2014 Elsevier B.V.

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