Epigenetics and Autoimmune Thyroid Diseases

Abstract

Increasing evidence suggests that epigenetic modifications, including changes in DNA methylation, covalent modifications of histone tails, and gene silencing mediated by non-coding RNA molecules, play a substantial role in the pathogenesis of autoimmune disorders and might be seen as the result of environmental insults that trigger these conditions. Studies in cells and tissues of patients with autoimmune thyroid diseases (AITD), and particularly in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are increasingly revealing altered epigenetic marks and resultant deregulation of gene expression levels, but the available data are still limited to be translated into the clinical settings. Particularly, genome-wide methylation and histone tail modification screenings are limited to a few studies in GD patients, and the diagnostic values of the observed epigenetic changes or their potential prognostic utility are still unclear. Similarly, data concerning microRNA expression in AITD patients are largely descriptive and not yet translated into the clinics. In addition, studies relating certain environmental exposures to specific epigenetic changes in AITD and studies evaluating the crosstalk between different epigenetic mechanisms are largely missing. In summary, despite that there is a clear evidence of epigenetic impairment in AITD, further research is required for a better understanding of the epigenetic networks involved in disease pathogenesis, thereby opening the way for potential diagnostic and prognostic tools, as well as for epigenetic interventions in the patients.

Primary Microcephaly with Novel Variant of MCPH1 Gene in Twins: Both Manifesting in Childhood at the Same Time with Hashimoto's Thyroiditis

“…15,16 Other reports have confirmed the thesis that immune defects in groups of patients may raise from environmental factors in individuals with genetic susceptibility. 15,16,36,37 To confirm the familiar predisposition of HT, there is a recent study of Kust and Matesa 38 conducted in 39 patients with a positive family history of HT, in comparison with a control group of affected patients without family history of the disorder: family positive history was found in 17 patients compared with 7 of the control group (p ¼ 0.0262), confirming the genetic predisposition of HT. The coincidence of the onset of the thyroid disorder in the twins is difficult to explain.…”

DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease

“…It is worth mentioning that the number of studies describing alterations in DNA methylation in AITD patients is also small . In previous genome‐wide analysis of DNA methylation in peripheral blood cells of patients with GD, 82 hypermethylated (such as DNMT1, MECP2, ADRB2, B3GNT2 and TNFRSF25) and 103 hypomethylated genes (including ICAM1) were described, with differentially methylated CpG sites being detected between CD4+ and CD8+ T cells .…”

“…It is worth mentioning that the number of studies describing alterations in DNA methylation in AITD patients is also small. 41,42 In previous genome-wide analysis of DNA methylation in peripheral blood cells of patients with GD, 82 hypermethylated (such as DNMT1, MECP2, ADRB2, B3GNT2 and TNFRSF25) and 103 hypomethylated genes (including ICAM1) were described, 43 with differentially T A B L E 1 Demographic, clinical and laboratory data of study groups, given as mean ± standard error of the mean or frequencies methylated CpG sites being detected between CD4+ and CD8+ T cells. 44 Besides, ICAM-1 gene promoter hypomethylation was further evidenced in both GD and HT patients, 30 whereas methylation levels of specific CpG sites in the TNFA and IFNG genes were found significantly different in patients with AITD, depending on disease prognosis and the presence of specific TNFA gene polymorphisms.…”

Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model

“…In general female-bias in autoimmunity is explained by stronger humoral and cellular immune responses of females due to sex hormone and x-chromosomal dependent mechanisms 35 . However, sex-based immune mechanisms leading to female-bias in thyroid autoimmunity are poorly understood 36 – 39 . It appears that potential sex dependent mechanisms which would have caused female-bias in autoimmunity did not take effects in the GO mouse model.…”