Review Article

Epigenetics and Autoimmune Diseases

Table 2

Summary of epigenetic mechanisms involved in autoimmune diseases.

        DNA methylation

Systemic lupus eErithematosusGlobal Hypomethylation of promoter region of genes: References
ITGAL [23]
CD40LG [24]
PRF1 [25]
CD70 [26]
IFGNR2 [27]
MMP14 [27]
LCN2 [27]
Ribosomal RNA gene promoter (18S and 28S) [27]
e1B promoter of CD5 in resting B cells [28]

Rheumatoid arthritisHypomethylation:
CpG islands upstream of an L1 open-reading frame [29]
IL-6 promoter gene in monocytes [30]
Hypermethylation:
Promoter of death receptor 3 (DR-3) [31]

Type 1 diabetesGlobal hypermethylation by altered metabolism of homocysteine [32]

Multiple sclerosisHypomethylation of promoter region of peptidyl arginine deiminase type II (PAD2) [33]

Systemic sclerosisHypermethylation of CpG islands in Fli1 promoter [34]

       Histone modification

Systemic lupus erithematosusPredisposition to apoptotic nucleosomes    
H3K4me3
H4K8 triacetylation
H3K27me3 [35]
H2BK12ac
Global acetylation of histone H3 and H4 in active CD4+ T cells [36]

Rheumatoid arthritis HDAC inhibitors:
Block induction of MMPs [37]
Repress of ADAMTs enzymes
Hyperacetylation of histones induces p16 and p21 [38]

Type 1 diabetesIncrease H3K9me2 in lymphocytes genes:
CLTA4
TGF-B
NF-κB [39]
p38
IL-6
Hyperglcemia causes H3K4 and H3K9 methylation [40]

Multiple sclerosisHyperacetylation of H3 promoter region in white matter [41]

          miRNAs

Systemic lupus ErithematosusDecreased expression:
miR-146a [42]
miR-125a [43]
Upregulation:
miR-21 and miR-148a [44]
miR-155 [45]

Rheumatoid arthritisOverexpression:
miR-155 [46]
miR-203 [47]
miR-146 [48]
Decreased expression of miR-124 [49]

Multiple sclerosisUpregulation:
miR-326[50]
miR-34a [51]
miR-155 [51]
Expression in Treg cells: miR-17-5p, miR-497, miR-193 and miR-126 [52]
Disease Relapse: miR-18b and miR-599
Disease Remission: miR-96
[53]
Brain-specific: miR-124 [54]

Type 1 diabetesOverexpression of miRNA-510 [55]
Decreased expression of miRNA-342 and miRNA-191 [55]
Beta cell failure: miR-21, miR-34a, and miR-146a [56]

Sjögren’s syndromeOverexpression: miR-547-3p and miR-168-3p [57]
Upregulated: miR-150 and miR-149 [57]