The Experts below are selected from a list of 11574 Experts worldwide ranked by ideXlab platform
Y. Shoenfeld - One of the best experts on this subject based on the ideXlab platform.
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Vaccine-induced autoimmunity: the role of Molecular Mimicry and immune crossreaction
Cellular & Molecular Immunology, 2018Co-Authors: Yahel Segal, Y. ShoenfeldAbstract:Since the early 1800s vaccines have saved numerous lives by preventing lethal infections. However, during the past two decades, there has been growing awareness of possible adverse events associated with vaccinations, cultivating heated debates and leading to significant fluctuations in vaccination rates. It is therefore pertinent for the scientific community to seriously address public concern of adverse effects of vaccines to regain public trust in these important medical interventions. Such adverse reactions to vaccines may be viewed as a result of the interaction between susceptibility of the vaccinated subject and various vaccine components. Among the implicated mechanisms for these reactions is Molecular Mimicry. Molecular Mimicry refers to a significant similarity between certain pathogenic elements contained in the vaccine and specific human proteins. This similarity may lead to immune crossreactivity, wherein the reaction of the immune system towards the pathogenic antigens may harm the similar human proteins, essentially causing autoimmune disease. In this review, we address the concept of Molecular Mimicry and its application in explaining post vaccination autoimmune phenomena. We further review the principal examples of the influenza, hepatitis B, and human papilloma virus vaccines, all suspected to induce autoimmunity via Molecular Mimicry. Finally, we refer to possible implications on the potential future development of better, safer vaccines.
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Pancreatitis after human papillomavirus vaccination: a matter of Molecular Mimicry
Immunologic Research, 2017Co-Authors: Mojca Bizjak, Or Bruck, Sonja Praprotnik, Shani Dahan, Y. ShoenfeldAbstract:A 20-year-old man developed severe abdominal pain 1 week after being vaccinated with the first dose of quadrivalent human papillomavirus (HPV) vaccine (Gardasil^®). Despite ongoing symptoms of nausea and pain, he received the second dose of the vaccine. Only 10 days later, laboratory results revealed significantly elevated pancreatic enzymes, and with concomitant abdominal pain and vomiting, he was diagnosed with acute pancreatitis. This case of acute pancreatitis after HPV vaccination is not a novel entity. Although confirming the relationship between pancreatitis and vaccine is challenging, some factors suggest a possible link, including the positive re-challenge upon repeated exposure to the vaccine, HPV vaccine as probable causal relationship to other autoimmune diseases and a probable mechanism of Molecular Mimicry. In conjunction with aluminum adjuvant, the induction of immunity through Molecular Mimicry may potentially culminate in production of cytotoxic autoantibodies with a particular affinity for pancreatic acinar cells.
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Molecular Mimicry in systemic lupus erythematosus
Lupus, 2009Co-Authors: Nancy Agmon-levin, Michael Blank, Ziv Paz, Y. ShoenfeldAbstract:Systemic lupus erythematosus is a multi-systemic autoimmune disease distinguished by the presence of various autoantibodies. Like most autoimmune diseases, systemic lupus erythematosus is believed to be induced by a combination of genetic, immunologic, and environmental factors, mainly infectious agents. Molecular Mimicry between an infectious antigen and self-components is implicated as a pivotal mechanism by which autoimmune diseases such as systemic lupus erythematosus are triggered. Here we review the current evidence of Molecular Mimicry between different infectious agents and systemic lupus erythematosus.
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Molecular Mimicry and auto-immunity.
Clinical reviews in allergy & immunology, 2007Co-Authors: Miri Blank, Ori Barzilai, Y. ShoenfeldAbstract:The term “Molecular Mimicry” was coined by R. Damian in 1964, who was first to suggest that antigenic determinants of micro-organisms may resemble antigenic determinants of their host. Damian suggested that this similarity served as a defense mechanism of a microorganism from the host’s immune system and prevented the development of immune response to the micro-organism, thereby protecting it from host defense. Years later, the term “Molecular Mimicry” was attributed a different meaning—namely, antigenic determinants of microorganisms might elicit an auto-immune response that harms the host. The concept of Molecular Mimicry is based on a structural similarity between a pathogen or metabolite and self-structures. The similarity could be expressed as shared amino acid sequences (linear or mimotope) or similar conformational structure between a pathogen and self-antigen.
Reinhard Hohlfeld - One of the best experts on this subject based on the ideXlab platform.
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Molecular Mimicry in Multiple Sclerosis
The New England journal of medicine, 2003Co-Authors: Hartmut Wekerle, Reinhard HohlfeldAbstract:Molecular Mimicry is a model in which foreign antigens are sufficiently similar to native antigens to trigger an autoimmune response. A study involving the specificity of a T-cell receptor derived from a patient with multiple sclerosis indicates that Molecular Mimicry extends to complexes of proteins — a finding with implications for therapy.
Jon D Laman - One of the best experts on this subject based on the ideXlab platform.
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the guillain barre syndrome a true case of Molecular Mimicry
Trends in Immunology, 2004Co-Authors: Wim C Ang, Bart C Jacobs, Jon D LamanAbstract:Molecular Mimicry between microbial antigens and host tissue forms an attractive hypothetical mechanism for the triggering of autoimmune disease by preceding infections. Recent crucial reviews state that Molecular Mimicry, as the causative mechanism, remains unproven for any human autoimmune disease. However, the peripheral neuropathy Guillain-Barre syndrome (GBS) is largely overseen in this debate. Based on recent evidence, we argue that GBS should be considered as an excellent paradigm and an attractive model for elucidation of both host and microbial aspects of Molecular Mimicry.
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The Guillain–Barré syndrome: a true case of Molecular Mimicry
Trends in immunology, 2004Co-Authors: C. Wim Ang, Bart C Jacobs, Jon D LamanAbstract:Molecular Mimicry between microbial antigens and host tissue forms an attractive hypothetical mechanism for the triggering of autoimmune disease by preceding infections. Recent crucial reviews state that Molecular Mimicry, as the causative mechanism, remains unproven for any human autoimmune disease. However, the peripheral neuropathy Guillain-Barre syndrome (GBS) is largely overseen in this debate. Based on recent evidence, we argue that GBS should be considered as an excellent paradigm and an attractive model for elucidation of both host and microbial aspects of Molecular Mimicry.
Robert S. Fujinami - One of the best experts on this subject based on the ideXlab platform.
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Molecular Mimicry as a Mechanism of Autoimmune Disease
Clinical Reviews in Allergy & Immunology, 2012Co-Authors: Matthew F. Cusick, Jane E. Libbey, Robert S. FujinamiAbstract:A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is Molecular Mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular Mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for Molecular Mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about Molecular Mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including Molecular Mimicry, dual TCRs, and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases.
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3 – Molecular Mimicry
Autoantibodies, 2007Co-Authors: Lisa K. Peterson, Robert S. FujinamiAbstract:Molecular Mimicry is the occurrence of common B or T cell reactive epitopes between microorganisms or environmental agents and the host, and the pathogenic consequence of such cross-reactivity. Molecular Mimicry has been demonstrated to occur in several different forms including complete identity at the protein level, homology at the protein level, similarity at the level of amino acid sequences and structural similarity. Identification of cases of Molecular Mimicry as a cause of autoimmunity can aid in the prevention, prognosis and treatment of patients with autoimmune disease. For the conclusion that Molecular Mimicry causes autoimmune disease, several criteria must be fulfilled: (1) similarity between a host epitope and an epitope in a microorganism or environmental agent, (2) antibodies or T cells cross-reactive with both epitopes detected in patients with the autoimmune disease, (3) an epidemiological link between exposure to the environmental agent or microbe and the development of autoimmune disease and (4) reproducibility of autoimmunity in an animal model following sensitization with the epitopes, infection with the microbe or exposure to the environmental agent. Few proposed Molecular mimics have been shown to fulfill all these criteria. However, Campylobacter jejuni lipooligosaccharide (LOS) Mimicry of human GM1 ganglioside and Mimicry between the dietary antigen butyrophilin and myelin oligodendrocyte glycoprotein provide examples that fulfill all the criteria, thus providing support for Molecular Mimicry as a viable mechanism for the development of autoimmune disease.
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Molecular Mimicry in multiple sclerosis.
International review of neurobiology, 2007Co-Authors: Jane E. Libbey, Lori L. Mccoy, Robert S. FujinamiAbstract:One of the most common demyelinating central nervous system (CNS) diseases in humans is multiple sclerosis (MS). The disease can be very debilitating with vision loss, motor and sensory disturbances, and cognitive impairment. The clinical course may present as a relapsing‐remitting disease course, a progressive disease course, or a combination thereof. The etiology of MS is unknown. Though many viruses have been shown to be associated with MS, no one virus has ever been demonstrated to be the cause of MS. In addition, MS is thought to have an autoimmune component. Molecular Mimicry is one hypothesis put forth which could reconcile the diverse pathology and etiology of MS. Molecular Mimicry occurs when peptides from pathogens share sequence or structural similarities with self‐antigens. Infection with various pathogens, each with its individual Molecular mimic to a CNS antigen, may explain the inability of investigators to link one specific virus to MS. Molecular Mimicry may be mediated through human leukocyte antigen class I‐ and class II‐restricted T cells and antibodies, which may explain the diversity in phenotype. Aspects of Molecular Mimicry will be discussed in relation to each of these immune system components. Examples of various Molecular mimics will be discussed with a particular focus on the CNS and MS. Molecular Mimicry alone may not be able to induce disease; priming of the immune system by infection with a pathogen that carries a Molecular mimic to self may have to be followed by a later nonspecific immunologic challenge in order for disease to be initiated. Recent research into this priming and triggering of disease will be discussed in relation to an animal model for MS.
Roland Martin - One of the best experts on this subject based on the ideXlab platform.
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Molecular Mimicry in multiple sclerosis
Autoimmunity, 2006Co-Authors: Mireia Sospedra, Roland MartinAbstract:Two main etiological components are considered important in human autoimmune diseases including multiple sclerosis (MS), first the immunogenetic background and second environmental factors. Among the latter, infectious organisms are probably the most relevant, and epidemiological studies in MS firmly support that viral infections often precede disease exacerbations or the onset of MS. Infectious agents can contribute to disease development or phenotypic expression in different ways. Our focus will be directed on Molecular Mimicry, i.e. antigenic similarity between structural epitopes or peptide sequences from infectious organisms with those found in self proteins of the host. The intriguing concept of Molecular Mimicry has evolved substantially since its introduction over 20 years ago. We will summarize the most important developments and discuss puzzling questions, which remain open despite many claims that Molecular Mimicry is involved in the development of human autoimmune disease after infections or vaccinations.
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Molecular Mimicry and antigen specific t cell responses in multiple sclerosis and chronic cns lyme disease
Journal of Autoimmunity, 2001Co-Authors: Roland Martin, Bruno Gran, Yingdong Zhao, Silva Markovicplese, Bibiana Bielekova, Adriana Marques, Myonghee Sung, Bernhard Hemmer, Richard Simon, Henry F McfarlandAbstract:Abstract The concept of Molecular Mimicry provides and elegant framework as to how cross-reactivity between antigens from a foreign agent with self proteins may trigger autoimmune diseases. While it was previously thought that sequence and structural homology between foreign and self proteins or the sharing of T cell receptor (TCR) and MHC-binding motifs are required for Molecular Mimicry to occur, we have shown that even completely unrelated peptide sequences may lead to cross-recognition by T cells. The use of synthetic combinatorial peptide libraries in the positional scanning format (PS-SCL) together with novel biometric prediction approaches has allowed us to describe the recognition profiles of individual autoreactive T cell clones (TCC) with unprecedented accuracy. Through studies of myelin-specific TCC as well as clones from the nervous system of patients suffering from chronic central nervous (CNS) Lyme disease it has become clear that at least some T cells are more degenerate than previously anticipated. These data will not only help us to redefine what constitutes specific T cell recognition, but also allow us to study in more detail the biological role of Molecular Mimicry. A recent clinical trial with an altered peptide ligand (APL) of one of the candidate myelin basic protein (MBP) epitopes in MS (amino acids 83–99) has shown that such a modified MBP peptide may not only have therapeutic efficacy, but also bears the potential to exacerbate disease. Thus, we provide firm evidence that the basic principles of cross-recognition and their pathogenetic significance are relevant in MS.
