Genetics and Epigenetics of Autoimmune Diseases

Konsta, Orsia D; Dantec, Christelle Le; Brooks, Wesley H.; Renaudineau, Yves

doi:10.1002/9780470015902.a0023593

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…In conclusion, three scenarios ca be proposed in order to explain how viruses could contribute to the emergence of RA in genetically predisposed individuals Konsta et al [20]. First, in the absence of a defined pathogen, RA development at the early stage may result from a polyviral community such as CMV plus EBV, or the cumulative effect of several microbial/viral factors.…”

Section: Resultsmentioning

confidence: 99%

How Herpesviridae Combined with other Viral Infections can Trigger and Drive Rheumatoid Arthritis

Arleevskaya¹,

Кравцова²,

Tsibulkin³

et al. 2016

Lupus Open Access

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Rheumatoid arthritis (RA) development results from an inadequate immune response to environmental challenges in genetically predisposed patients. The list of viruses associated with RA is still growing, and includes the cytomegalovirus, the Epstein-Barr virus, and the herpes simplex viruses. Several hypotheses support their causative role. Firstly, RA development may result from a polyviral community or the cumulative effect of several microbial/viral factors thus explaining the absence of a single defined pathogen. Secondly, the process of RA development from preclinical to late-stage disease may result from cumulative episodes of viral infections caused by distinct pathogens. Thirdly, viral agents may trigger RA when associated with other factors such as tobacco, ethnic differences, psychological stress, inflammation, or chronic joint tissue micro-trauma. On the other hand, others consider that RA development occurs even with ordinary infection frequency and duration and results from immune hypersensitivity to viral infections which can lead to loss of tolerance to self-antigens.

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Section: Resultsmentioning

confidence: 99%

How Herpesviridae Combined with other Viral Infections can Trigger and Drive Rheumatoid Arthritis

Arleevskaya¹,

Кравцова²,

Tsibulkin³

et al. 2016

Lupus Open Access

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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%

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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“…Upto forty non-HLA genetic associations were characterized in SLE and pSS, and the list is growing with development of genome wide association studies (GWAS) and next-generation sequencing (NGS) technologies which contribute to the characterization of rare single nucleotide polymorphisms (SNPs), new copy number variations (CNV) and microsatellites [23]. The development of the ENCODE (Encyclopedia of DNA elements) and roadmap Epigenomic programs were decisive for our comprehension of the associated causal genetic risk-factors revealing that they are present predominantly within cellspecific long range gene-regulatory sequences which are located outside promoters, protein coding regions, splice junctions, and 3' UTRs [24].…”

Section: Geneticsmentioning

confidence: 99%

“…Histone acetylation is effective to control long-range regulatory sequences by controlling transcription factor binding and in turn transcription. However, such control may be altered in the case of genetic risk variants and such effect would predominantly affect B cells in both SLE and pSS [23], while it is T cells that are affected in nearly all AID [1].…”

Section: Geneticsmentioning

confidence: 99%

Similarities and Differences of Epigenetic Mechanisms in Lupus and Sjogren's Syndrome

Charras²,

Brooks³

et al. 2016

Lupus Open Access

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Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome are two systemic autoimmune diseases, which are believed to develop when genetically predisposed individuals undergo epigenetic modifications in response to environmental factors. Recent advances in the understanding of the pathophysiology of these two diseases suggest a multi-step process involving environmental factors leading to distinct cell specific deregulation of the epigenetic machinery, and the effect is reinforced in those patients with risk variants mapping to epigenetically-controlled immune regulators. Finally, it was observed that the PKC-delta/Erk/DNMT1 pathway was altered in both diseases and the effects could be reversed thus providing arguments to suggest that therapeutic strategies targeting this pathway would be effective in both diseases.

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Genetics and Epigenetics of Autoimmune Diseases

Cited by 15 publications

References 49 publications

How Herpesviridae Combined with other Viral Infections can Trigger and Drive Rheumatoid Arthritis

How Herpesviridae Combined with other Viral Infections can Trigger and Drive Rheumatoid Arthritis

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

Similarities and Differences of Epigenetic Mechanisms in Lupus and Sjogren's Syndrome

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