Epigenetic Therapeutics in Autoimmune Disease

Szyf, Moshe

doi:10.1007/s12016-009-8172-8

Cited by 49 publications

(55 citation statements)

References 198 publications

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“…HDAC inhibition is also effective in the treatment of juvenile idiopathic arthritis [33]. Additionally, potential therapeutic roles for DNA demethylation inhibitors are currently being investigated, and MBD2 was recently proposed as a candidate target [34]. …”

Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

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Background: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development. Methods and Results: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6-fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001). Conclusions: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development.

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Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

View full text Add to dashboard Cite

show abstract

“…Map epigenetic modification patterns in a given cell (either of immune system or target organ) it is critically important because epigenetic biomarkers can be used for clinical prediction, diagnosis, and therapeutic development [8,11,18,45]. Moreover, epigenetic states are potentially reversible and hence candidates for pharmacological intervention [134,135]. Specifically, epigenetic modulators recently developed as drugs, are such target proteins controlling chromatin [i.e.…”

Section: Epigenetic Differentiation Therapiesmentioning

confidence: 99%

The epigenetics of PBC: The link between genetic susceptibility and environment

Marzorati

Lleo

Carbone

et al. 2016

Clinics and Research in Hepatology and Gastroenterology

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“…In addition, suberorylanide hydroxamic acid (SAHA), a HDAC inhibitor, in combination with TSA can reduce IL-6, IL-12, IFN-γ, and IL-10 production leading to a decrease in inflammation response as well as decreases in proteinuria and glomerulonephritis in murine models [3,4]. Due to the effects of HDACi in their ability to reduce inflammation in murine models, researchers have postulated their use for patients to control inflammation such as those that occur with SLE [5][6][7][8]. However, studies regarding HDAC expression levels in patients with SLE are lacking.…”

Section: Resultsmentioning

confidence: 99%

Untitled

2015

J Rheum Dis Treat

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There is increasing evidence that epigenetic factors may play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Both global and gene specific methylation is known to occur in lupus patients, as well as, changes in histone acetylation status. Histone acetylation is associated with active chromatin or activation of genes, whereas histone deacetylase (HDAC) activity is associated with silencing of genes. Therefore, HDACs have been targeted as potential therapeutic targets for a number of diseases, including lupus. The purpose of this study was to determine histone deacetylase (HDAC) expression in patients who are diagnosed with SLE compared to age-matched healthy controls. Quantitative real-time PCR expression levels of HDAC 1, HDAC 2 and HDAC 7 were investigated in peripheral blood mononuclear cells of African American and European American women. Our results showed that HDAC 1 expression is significantly (p < 0.0039) elevated in lupus patients compared to controls. HDAC 2 expression is also increased in lupus patients (p < 0.0427). However, HDAC 7 showed no significant difference (p < 0.4644) in expression in our SLE patients compared to their controls. Those lupus patients with a SLE disease activity index (SLEDAI) of 4 or greater showed lower expression of HDAC 1 (p < 0.0026) compared to those with modest disease and a SLEDAI of less than 4. However, in those lupus patients with a SLEDAI of 4 or greater showed increased expression of HDAC2 (p < 0.053) when compared to those with a SLEDAI of less than 4. This observation was also noted in HDAC7. Increased expression in HDAC 1 and 2 has been associated with induced kidney injury and induction of proinflammatory cytokines.

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Epigenetic Therapeutics in Autoimmune Disease

Cited by 49 publications

References 198 publications

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

The epigenetics of PBC: The link between genetic susceptibility and environment

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