Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Oldstone, Michael B. A.

doi:10.1089/mab.2013.0090

Cited by 59 publications

(54 citation statements)

References 45 publications

(63 reference statements)

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“…It is known that the molecular mimicry between virus antigens and self-antigens may disrupt self-tolerance, allowing for the host to produce autoantibodies to cause a transient autoimmune response (41). However, unless the patient has genetic abnormalities, self-tolerance will be restored after the antigen has been cleared; hence, autoantibodies may not continue to be present in the immune system (42).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mimicry between Dengue Virus and Coagulation Factors Induces Antibodies To Inhibit Thrombin Activity and Enhance Fibrinolysis

Chuang

Lin

Liu

et al. 2014

J Virol

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Dengue virus (DENV) is the most common cause of viral hemorrhagic fever, and it may lead to life-threating dengue hemorrhagic fever and shock syndrome (DHF/DSS). Because most cases of DHF/DSS occur in patients with secondary DENV infection, anti-DENV antibodies are generally considered to play a role in the pathogenesis of DHF/DSS. Previously, we have found that antithrombin antibodies (ATAs) with both antithrombotic and profibrinolytic activities are present in the sera of dengue patients. However, the mechanism by which these autoantibodies are induced is unclear. In this study, we demonstrated that antibodies induced by DENV immunization in mice and rabbits could bind to DENV antigens as well as to human thrombin and plasminogen (Plg). The binding of anti-DENV antibodies to thrombin and Plg was inhibited by preadsorption with DENV nonstructural protein 1. In addition, affinity-purified ATAs from DENV-immunized rabbit sera could inhibit thrombin activity and enhance Plg activation both in vitro and in vivo. Taken together, our results suggest that molecular mimicry between DENV and coagulation factors can induce the production of autoantibodies with biological effects similar to those of ATAs found in dengue patients. These coagulation-factor cross-reactive anti-DENV antibodies can interfere with the balance of coagulation and fibrinolysis, which may lead to the tendency of DHF/DSS patients to bleed. IMPORTANCE Dengue virus (DENV) infection is the most common mosquito-borne viral disease in tropical and subtropical areas. Over 50million DENV infection cases develop each year, and more than 2.5 billion people are at risk of dengue-induced hemorrhagic fever and shock syndrome. Currently, there is no vaccine or drug treatment for DENV. In the present study, we demonstrated that DENV immunization could induce thrombin and plasminogen (Plg) cross-reactive antibodies, which were able to inhibit thrombin activity and enhance Plg activation. These results suggest that molecular mimicry between DENV antigens, thrombin, and Plg may elicit antibodies that disturb hemostasis. The selection of appropriate candidate antigens for use in DENV vaccines should prevent these potentially dangerous autoimmune responses.

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Section: Discussionmentioning

confidence: 99%

Molecular Mimicry between Dengue Virus and Coagulation Factors Induces Antibodies To Inhibit Thrombin Activity and Enhance Fibrinolysis

Chuang

Lin

Liu

et al. 2014

J Virol

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“…The targeted epitopes in the pathogen may be similar to epitopes in one of the host's molecules, perhaps differing in only one amino acid in the sequence or a slight variation in the topology [57]. In such a situation, an infection could lead to an autoimmune reaction as the adaptive immune response initiated against the pathogen spreads to autoantigens that may be in greater abundance and greater distribution in the host.…”

Section: The Bmolecular Mimicry^hypothesismentioning

confidence: 99%

A Review of Autoimmune Disease Hypotheses with Introduction of the “Nucleolus” Hypothesis

Brooks

2016

Clinic Rev Allerg Immunol

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Numerous hypotheses have been proposed in order to explain the complexity of autoimmune diseases. These hypotheses provide frameworks towards understanding the relations between triggers, autoantigen development, symptoms, and demographics. However, testing and refining these hypotheses are difficult tasks since autoimmune diseases have a potentially overwhelming number of variables due to the influence on autoimmune diseases from environmental factors, genetics, and epigenetics. Typically, the hypotheses are narrow in scope, for example, explaining the diseases in terms of genetics without defining detailed roles for environmental factors or epigenetics. Here, we present a brief review of the major hypotheses of autoimmune diseases including a new one related to the consequences of abnormal nucleolar interactions with chromatin, the "nucleolus" hypothesis which was originally termed the "inactive X chromosome and nucleolus nexus" hypothesis. Indeed, the dynamic nucleolus can expand as part of a cellular stress response and potentially engulf portions of chromatin, leading to disruption of the chromatin. The inactive X chromosome (a.k.a. the Barr body) is particularly vulnerable due to its close proximity to the nucleolus. In addition, the polyamines, present at high levels in the nucleolus, are also suspected of contributing to the development of autoantigens.

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“…One of the proposed mechanisms is termed as ‘antigen mimicry’, that is, similarity between epitopes of autoantigens and epitopes of harmless environmental antigens. So, the pathogenic microbes might activate the APCs and cause abnormal presentation and processing of self antigens, thereby initiating autoimmunity and chronic intestinal inflammation [59]. …”

Section: Pathogenesismentioning

confidence: 99%

Immunopathogenesis and therapeutic approaches in pediatric celiac disease

Agarwal

Kovilam

Zach

et al. 2016

Expert Review of Clinical Immunology

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Summary Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients.

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Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cause of Autoimmune Diseases

Cited by 59 publications

References 45 publications

Molecular Mimicry between Dengue Virus and Coagulation Factors Induces Antibodies To Inhibit Thrombin Activity and Enhance Fibrinolysis

Molecular Mimicry between Dengue Virus and Coagulation Factors Induces Antibodies To Inhibit Thrombin Activity and Enhance Fibrinolysis

A Review of Autoimmune Disease Hypotheses with Introduction of the “Nucleolus” Hypothesis

Immunopathogenesis and therapeutic approaches in pediatric celiac disease

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