Epigenetics changes associated to environmental triggers in autoimmunity

Cañas, Carlos A.; Cañas, Felipe; Bonilla-Abadía, Fabio; Ospina, Fabio E.; Tobón, Gabriel J.

doi:10.3109/08916934.2015.1086996

Cited by 46 publications

(30 citation statements)

References 136 publications

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“…Systemic autoimmune diseases develop as multistep processes through a complex interplay between genetic and environmental factors, including infections, ultraviolet light (in the case of SLE), smoking (in rheumatoid arthritis), and certain medications (in the case of SLE and AAV) 59 . These factors can induce cellular damage through various mechanisms and increase the exposure of the immune cells to autoantigens 60 .…”

Section: Systemic Autoimmune Diseasesmentioning

confidence: 99%

The role of neutrophils and NETosis in autoimmune and renal diseases

2016

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Systemic autoimmune diseases are a group of disorders characterized by a failure in self-tolerance to a wide variety of autoantigens. In genetically predisposed individuals, these diseases occur as a multistep process in which environmental factors have key roles in the development of abnormal innate and adaptive immune responses. Experimental evidence collected in the past decade suggests that neutrophils — the most abundant type of white blood cell — might have an important role in the pathogenesis of these diseases by contributing to the initiation and perpetuation of immune dysregulation through the formation of neutrophil extracellular traps (NETs), synthesis of proinflammatory cytokines and direct tissue damage. Many of the molecules externalized through NET formation are considered to be key autoantigens and might be involved in the generation of autoimmune responses in predisposed individuals. In several systemic autoimmune diseases, the imbalance between NET formation and degradation might increase the half-life of these lattices, which could enhance the exposure of the immune system to modified autoantigens and increase the capacity for NET-induced organ damage. This Review details the role of neutrophils and NETs in the pathophysiology of systemic autoimmune diseases, including their effect on renal damage, and discusses neutrophil targets as potential novel therapies for these diseases.

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Section: Systemic Autoimmune Diseasesmentioning

confidence: 99%

The role of neutrophils and NETosis in autoimmune and renal diseases

2016

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“…Recent studies propose that environmental factors can interact with susceptibility genes to produce a synergistic effect in triggering diseases through epigenetic modulation (62–64). Epigenetics aim to study how non-genetic factors regulate the gene expressions and phenotypes and their roles in the development of diseases without involving alterations of the DNA sequence (65).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, genes involved in the immune system or thyroid can be regulated by epigenetic mechanisms, and dysfunctions of these genes caused by epigenetics can further result in autoimmune diseases. In the past decade, epigenetics have been considered to have key roles in integrating genetic and environmental factors in human complex diseases including autoimmune diseases (64, 70, 71). In the past decade, increasing evidence has suggested the critical roles of epigenetics in the pathogenesis of AITD, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD (42, 60, 72–75).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

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Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell-mediated organ-specific autoimmune diseases. Graves’ disease and Hashimoto thyroiditis are the two main clinical presentations of AITD. Both genetic and environmental factors have important roles in the development of AITD. Epigenetics have been considered to exert key roles in integrating those genetic and environmental factors, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD. Recent studies on the epigenetics of AITD have provided some novel insights into the pathogenesis of AITD. The aim of this review is to provide an overview of recent advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone modifications, and non-coding RNAs. This review highlights the key roles of epigenetics in the pathogenesis of AITD and potential clinical utility. However, the epigenetic roles in AITD are still not fully elucidated, and more researches are needed to provide further deeper insights into the roles of epigenetics in AITD and to uncover new therapeutic targets. Although there are many studies assessing the epigenetic modifications in AITD patients, the clinical utility of epigenetics in AITD remains poorly defined. More studies are needed to identify the underlying epigenetic modifications that can contribute to accurate diagnosis of AITD, adequate choice of treatment approach, and precise prediction of treatment outcomes.

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“…There is overwhelming evidence to support the premise that a variety of GAS antigens including the M protein and group A carbohydrate act as a major immunogen involved in initiating the inflammatory process due to the development of tissue cross-reactive antibodies and T cells generated during a GAS infection (4, 5). In humans, anti-streptococcal heart cross-reactive antibodies directed against the group A carbohydrate and cardiac myosin epitopes are believed to damage the valve endothelium (6, 7) and upregulate VCAM-1 (8), while T cells specific for streptococcal M protein and cardiac myosin epitopes enter through the activated endothelium of the valve (9, 10).…”

Section: Introductionmentioning

confidence: 99%

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

et al. 2016

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Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeat exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection.

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Epigenetics changes associated to environmental triggers in autoimmunity

Cited by 46 publications

References 136 publications

The role of neutrophils and NETosis in autoimmune and renal diseases

The role of neutrophils and NETosis in autoimmune and renal diseases

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

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