Yehuda Shoenfeld

Tel Aviv University | TAU · Faculty of Medicine

OBJECTIVES: The objective of this study was to assess the effect that triple therapy (anticoagulation plus CS plus plasma exchange and/or IVIGs) has on the mortality risk of patients with catastrophic APS (CAPS) included in the CAPS Registry. METHODS: Patients from the CAPS Registry were grouped based on their treatments: triple therapy; drugs inc...

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment....

Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-mo...

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by lymphocytic infiltration of the exocrine glands, and autoantibody production. Multiple environmental factors affecting an individual with a genetic susceptibility may trigger the development of SS. Herein, we aimed to evaluate links between the different pebbles in the mosa...

Sjögren's syndrome (SjS) is a systemic autoimmune disease with complex pathogenesis and still unknown etiology. Infections are listed among the main environmental factors triggering the disease in genetically predisposed individuals. Among other environmental factors, the role of immunization with vaccines in the etiopathogenesis of SjS has not yet...

The 'Task Force on Catastrophic Antiphospholipid Syndrome (CAPS)' was developed on the occasion of the 14th International Congress on Antiphospholipid Antibodies. The objectives of this Task Force were to assess the current knowledge on pathogenesis, clinical and laboratory features, diagnosis and classification, precipitating factors and treatment...

The recent CORA (Controversies in Rheumatology and Autoimmunity) meeting held in 2013 represented a unique opportunity for rheumatologists to address several topics. Among these, four topics include: (i) the role of epigenetic changes in the pathogenesis of rheumatoid arthritis (RA), as shown by studies in monozygotic twins; (ii) the cardiovascular...

Before the antibiotic era, treatment of tuberculosis patients was restricted to sun exposure in sanatoria. Years later, it was found that 1,25-dihydroxyvitamin D3 stimulates production of cathelicidins, a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes. Cathelicidins serve a critical role in innate immune d...

Introduction: Antiphospholipid syndrome (APS) is a systemic autoimmune disease representing the most frequent cause of acquired hypercoagulability and recurrent miscarriages. The disease has been known for at least 30 years, but its treatment is still a strongly debated topic for a number of reasons. First, it is difficult, if not impossible, to id...

Objectives: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. Methods: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical...

Fibromyalgia is a common chronic pain syndrome characterized by widespread pains and characteristic somatic symptoms. Current evidence suggests that cytokines and especially chemokines may have a role in the pathogenesis of this syndrome. Cytokines are small soluble factors that work as immune system messengers. They can be classified as pro-inflam...

In recognition of Open Access week (21st-27th October 2013), we asked some BMC Medicine Editorial Board Members to share their views and experiences on open access publishing. In this short video, they highlight the benefits of visibility and dissemination of their research, and discuss the future directions for this model of publishing.

Intravenous immunoglobulin (IVIG) is used successfully for therapy of inflammatory and autoimmune diseases, especially in cases of conventional therapy resistance. Within the broad spectrum of immunomodulatory activities of IVIG in vitro and in vivo, the anti-idiotypic activity, neutralizing the autoimmune disease related idiotypes, is one of the m...

The tegumentary system becomes a scenario for immune responses. The knowledge of these conditions has led to induction of complementary animal models, better knowledge of the pathophysiology, and new tools [1] for diagnosis and therapy of these autoimmune skin disorders. In this special issue from Autoimmune Diseases we have invited several papers...

Localized scleroderma is traditionally considered to be limited to the skin, subcutaneous tissue, underlying bone, and in the craniofacial subtype, also nervous system involvement. However, recent studies have also described other systemic manifestations in these patients. Despite many reports of neurological involvement in patients with the cranio...

We have read the letter by Bossuyt and Fieuws entitled ‘Detection of anti-nuclear antibodies, added-value of solid phase assay?’ with great interest.1 In this letter, the authors described a comparison between anti-nuclear antibodies (ANA) performed by indirect immunofluorescent assay (IIFA) and by an automated method (fluoroenzymeimmunoassay; EliA...

A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of patients with systemic lupus erythematosus (SLE) and correlates with the presence of autoantibodies. Antiphospholipid syndrome (APS) can develop secondary to SLE or as a primary disease. In the current study we investigated the ability of sera from patient...

This editorial refers to Low-dose aspirin versus low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial, in patients positive for antiphospholipid antibodies (ALIWAPAS), by Maria J. Cuadrado et al., doi:10.1093/rheumatology/ket313, on pages 275-84.

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 compone...

Epitope-antibody-reactivities (EAR) of intravenous immunoglobulins (IVIGs) determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning wit...

Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivi...

A six-month research period is a mandatory part of the residency training program in most basic specialties in Israel and is named: the "basic science period". This is the only period in an Israeli physician's medical career which is dedicated strictly to research, accentuating the importance of medical research to the quality of training and level...

The safety of 4 different adjuvants was assessed in lupus-prone BWF1 mice. Four groups of mice were intraperitoneally injected with incomplete Freund's adjuvant (IFA), or complete Freund's adjuvant (CFA), Squalene (SQU) or aluminum hydroxide (ALU). An additional group received plain PBS (UNT group). Mice were primed at week 9 and boosted every othe...

Background: Ferritin is an iron storage protein considered also as an acute phase reactant with high levels in various inflammatory conditions. Recently, a plausible role for ferritin in the pathogenesis of immune-mediated and especially autoimmune diseases has been suggested. However, the link between ferritin and the antiphospholipid syndrome (A...

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 infiltrati...

Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolismas well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activityappear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Mo...

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfacto...

ASIA syndrome, "Autoimmune (Auto-inflammatory) Syndromes Induced by Adjuvants" includes at least four conditions which share a similar complex of signs and symptoms and have been defined by hyperactive immune responses: siliconosis, macrophagic myofasciitis syndrome, Gulf war syndrome and post-vaccination phenomena. Exposure to adjuvants has been d...

Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. There are four uncommon medical conditions characterized by high levels of ferri...

It is astounding to consider that virtually, every textbook of physiology in every medical school in the world does not include a chapter on immunology. On the other hand, virtually, in every textbook in internal medicine, immunology and immune response overlaps with every tissue and every organ. Indeed, historically, the concept of the immune resp...

Post-vaccination autoimmune phenomena are a major facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and different vaccines, including HPV, have been identified as possible causes. The medical history of three young women who presented with secondary amenorrhea following HPV vaccination was collected. Data regarding type of v...

Immunology is a relatively new specialty. Ironically, the immune system impacts every physiological system in the body, but yet most textbooks of physiology do not include any functional aspects of the immune system. Indeed, with the exception of early descriptions of anaphylaxis and allergy, the majority of immune studies were focused on either th...

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy (a sudden weakening of posture muscle tone usually triggered by emotion) caused by the loss of orexin neurons in the hypothalamus. Autoimmune mechanisms are implicated in narcolepsy by increased frequency of specific HLA alleles and the presence of specific a...

Relapsing catastrophic antiphospholipid syndrome potential role of microangiopathic hemolytic anemia in disease relapses. Espinosa G, Rodríguez-Pintó I, Gomez-Puerta JA, Pons-Estel G, Cervera R; Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Collaborators (69)Cervera R, Espinosa...

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving multiple organs. One of the main sites of SLE morbidity is the central nervous system (CNS), specifically the brain. In this article we review several imaging modalities used for CNS examination in SLE patients. These modalities are categorized as morphological and functi...

The pathogenesis of autoimmune diseases (ADs) is characterized by a complex interaction between genetic, immune defects, environmental and hormonal factors. The concept of "mosaic of autoimmunity" deals with the multi-factorial origin and diversity of expression of ADs in humans. Genetic leads to a predisposition in developing an autoimmune syndrom...

This work was supported by Grant R01AT004321 (to K. D. Moudgil) from the National Institutes of Health, Bethesda, MD, USA. We thank all the authors who have contributed papers to this special issue.

Immune-mediated thrombocytopenic purpura (ITP) is recognized as a cell-specific autoimmune disorder, yet, multifactorial in origin. The development of thrombocytopenia is well proven to be mediated by both humoral (anti-platelet antibodies) and cellular (T-cell) mediated mechanisms. In some cases other autoantibodies are also induced, eg, antinucle...

In this Q&A, we talk to Professor Yehuda Shoenfeld about Autoimmune Syndrome Induced by Adjuvants (ASIA) and discuss his recommendations regarding further research in the field.

To investigate the association between human papillomavirus (HPV) vaccination and autoimmune manifestations compatible with systemic lupus erythematosus (SLE) or SLE-like disease, the medical history of six women who presented with SLE or SLE-like disease following HPV immunization was collected. Data regarding type of vaccine, number of immunizati...

We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of...

The identification of antinuclear antibodies (ANA) is an essential step in the diagnosis of different autoimmune diseases. The gold standard method for their detection is immunofluorescence assay. However, this is a subjective and laborious method, thus a need for simplified objective methods has aroused. In the current work, we evaluated such auto...

Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens. The pathogenic hypothesis comprises a complex interaction between genetic, environmental and hormonal factors that interact with an individual over time generating a dysregulation of the immune system leading to disease development. S...

Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to...

We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with β2-glycoprotein I (β2-GPI). Autoantibody...

The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naïve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intra-cerebra-ventricularly (ICV) with the...

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...

Sjögren's syndrome (SS) is a systemic progressive autoimmune disease characterized by a complex pathogenesis requiring a predisposing genetic background and involving immune cell activation and autoantibody production. The immune response is directed to the exocrine glands, causing the typical 'sicca syndrome', but major organ involvement is also o...

Parasitic infections may induce variable immunomodulatory effects and control of autoimmune disease. Toxoplasma gondii (T. gondii) is a ubiquitous intracellular protozoan that was recently associated with autoimmunity. This study was undertaken to investigate the seroprevalence and clinical correlation of anti-T. gondii antibodies in patients with...

Almost twenty five years ago the concept of "Mosaic of Autoimmunity" was introduced to the scientific community and since then it has continuously evolved adding new tesserae. We are looking now at an era in which the players of autoimmunity have changed names and roles. In this article collection on Autoimmunity, published in BMC Medicine, several...

The morbidity and mortality of systemic lupus erythematosus (SLE) is a subject of intense relevance in the literature, yet descriptions of prolonged and sustained remissions or even cure are barely reported. In recent decades the life expectancy in SLE patients has improved, but the quality of life seems to be poor compared with other chronic disea...

An adjuvant is a substance that enhances the antigen-specific immune response, induces the release of inflammatory cytokines, and interacts with Toll-like receptors and the NALP3 inflammasome. The immunological consequence of these actions is to stimulate the innate and adaptive immune response. The activation of the immune system by adjuvants, a d...

Clostridium difficile is the etiologic agent of nosocomial and community-acquired diarrhea associated with exposure to antibiotics that disrupt the normal colonic flora. As antibacterials currently used for primary C. difficile infections favor recurrences, new methods able to neutralize the bacterium without affecting the gut microbiota are badly...

Granulomatosis and angiitis (GPA) is a multisystemic disease characterized by a granulomatous inflammation, tissue necrosis, and vasculitis of small and medium-sized blood vessels. Although the disease has a predilection for the upper respiratory tract, lungs, and kidneys, any organ system may be affected. Here, we present a case of generalized GPA...

Evolving understanding of the role of helminths in the pathogenesis of autoimmunity has led to the development of novel therapeutic interventions that are showing promise in patients with immune-mediated diseases. Meanwhile, studies in animal models of arthritis suggest that these new products might also be applicable in autoimmune rheumatic diseas...

In the central nervous system (CNS) microglia are crucial for the defense of the brain against invading microorganisms, formation of tumors, and damage following trauma [1]. However, uncontrolled activation of these cells may have deleterious outcomes [2] through activation of Fcγ and the complement 3 receptors and the induction of an adaptive immu...

The incidence of autoimmune diseases is increasing in Western countries, possibly due to the improved sanitary conditions and reduced exposure to infections in childhood (the hygiene hypothesis). There is an ongoing debate whether infection prevents or precipitates autoimmune diseases. Various helminths species used in several animal models were sh...

Serine protease inhibitors (serpins) are evolutionary old, structurally conserved molecules which encompass nearly all branches of life. More than 1,000 serpins were characterized to date which are subdivided into 16 subgroups (A-P) according to their common ancestry; among them, 37 are found in humans. Serpins were termed after their capability to...

Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases...

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. Glomerulonephritis (GLN) is one of the major causes of morbidity and mortality in SLE. It has recently been demonstrated that adjuvants of vaccines could cause the so called ASIA syndrome. The study aimed to assess the effects of Complete Freund's Adjuvant (CF...

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 a...

Glucocorticoids (GC) are essential in the management of several medical conditions but its long-term use is associated with complications in diverse organs and systems. The aim of the present study is to review the long-term complications of past GC use. Permanent damage related to GC can affect patient's life even years after its withdrawal. Class...

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay meth...

Lately, vitamin D has been linked with metabolic and immunological processes, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and upon activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and othe...

The sense of smell is an ancient sensory modality vital for sampling and perceiving the chemical composition of surrounding environments. Olfaction involves a pathway of biochemical and electrophysiological processes, which allows the conversion of molecular information into sensations. Disturbances in the olfactory function have been investigated...

During the last decade it has been shown that some components of intravenous immunoglobulin (IVIG) are responsible for their broadly therapeutic application. Currently, such specific subfractions are defined as specific IVIG (sIVIG) and are affinity-purified from commercial IVIGs that target specific antigens/antibodies related to a specific autoim...

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. Once considered an exclusive cutaneous disorder, the neurologic involvement present in localized scleroderma has been described in several case reports. Seizures...

In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bl...