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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. Source

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. Source

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. Source

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. Source

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. Source

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