Altered patterns of epigenetic changes in systemic lupus erythematosus and auto-antibody production: Is there a link?

Thabet, Yosra; Cañas, Felipe; Ghedira, Ibtissem; Youinou, Pierre; Mageed, Rizgar A.; Renaudineau, Yves

doi:10.1016/j.jaut.2012.05.015

Cited by 38 publications

(18 citation statements)

References 64 publications

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“…These epigenetic chromosomal changes may also affect the generation of autoantibodies in the setting of obesity. It has been shown in both lupus and Sjogern's syndrome, two conditions characterized by the presence of ANAs and other auto-antibodies, that there are potentially pathologic epigenetic changes that are associated with auto-antibody production [36,37]. Given that epigenetic changes are implicated in the generation of autoimmunity, and that obesity has been linked to multiple epigenetic mechanisms, it is possible that nutritionally induced epigenetic changes are also driving autoimmunity in obese patients [38].…”

Section: Discussionmentioning

confidence: 99%

The Association between Anti-Nuclear Antibodies and Obesity is Likely Mediated by Abdominal Adiposity and Systemic Inflammation

Blanco¹,

Labitigan²,

Abramowitz³

2017

J Clin Cell Immunol

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Section: Discussionmentioning

confidence: 99%

The Association between Anti-Nuclear Antibodies and Obesity is Likely Mediated by Abdominal Adiposity and Systemic Inflammation

Blanco¹,

Labitigan²,

Abramowitz³

2017

J Clin Cell Immunol

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“…On the other hand, hypomethylated DNA and histone modifications are not only directly involved in SLE by regulating the susceptibility genes, but also directly linked to production of autoantibodies to nuclear antigens, such as DNA, chromatin, nucleosomes, histones, non-histone DNA binding proteins, and ribonucleoproteins, along with epigenetically modified ribonucleoprotein-derived peptides [Tan, 1989;Thabet et al, 2012]. Future work is needed to elucidate which epigenetic changes contribute to which subset of autoantibodies.…”

Section: Interaction Among Epigenetic Regulationsmentioning

confidence: 99%

Aberrant Epigenetic Regulation in the Pathogenesis of Systemic Lupus Erythematosus and Its Implication in Precision Medicine

Zhan

Guo²,

Lu³

2016

Cytogenet Genome Res

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Great progress has been made in the last decades in understanding the complex immune dysregulation in systemic lupus erythematosus (SLE), yet the efforts to pursue an effective treatment of SLE proved to be futile. The pathoetiology of SLE involves extremely complicated and multifactorial interaction among various genetic and epigenetic factors. Multiple gene loci predispose to disease susceptibility, and the interaction with epigenetic modifications mediated through sex, hormones, and the hypothalamo-pituitary-adrenal axis complicates susceptibility and manifestations of this disease. Finally, certain environmental and psychological factors probably trigger the disease via epigenetic mechanisms. In this review, we summarize and discuss recent epigenetic studies of SLE and suggest a personalized approach to the dissection of disease onset and therapy or precision medicine. We speculate that in the future, precision medicine based on epigenetic and genetic information could help guide more effective targeted therapeutic intervention.

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“…Since research into the genetics of most ADs has not yet discovered specific and predominant gene mutations that explain the diseases, the involvement of epigenetics in ADs is gaining interest [5][6][7][8][9][10][11][12]. Epigenetics, the reversible control of gene silencing and expression without alteration of the gene's DNA sequence, can provide connections between the many environmental factors associated with ADs to specific genes, even if those genes are not necessarily genetically aberrant.…”

Section: Hypotheses Of Autoimmune Diseasesmentioning

confidence: 99%

“…In addition, a hallmark of RA patients is an increase in citrullinated collagen while in MS patients, there is an increase in citrullinated myelin basic protein [26,27]. Several cellular mechanisms are suspected to lead to autoantibody production such as cellular stress, an abnormal apoptotic process, and/or a defective epigenetic mechanism [8,28].…”

Section: Hypotheses Of Autoimmune Diseasesmentioning

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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Altered patterns of epigenetic changes in systemic lupus erythematosus and auto-antibody production: Is there a link?

Cited by 38 publications

References 64 publications

The Association between Anti-Nuclear Antibodies and Obesity is Likely Mediated by Abdominal Adiposity and Systemic Inflammation

The Association between Anti-Nuclear Antibodies and Obesity is Likely Mediated by Abdominal Adiposity and Systemic Inflammation

Aberrant Epigenetic Regulation in the Pathogenesis of Systemic Lupus Erythematosus and Its Implication in Precision Medicine

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

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