2.3.1. Epigenetic biomarkers

Epigenetic biomarkers refer to the epigenetic changes that govern gene expression without changing the nucleotide sequence of the DNA and are specifically associated with disease development such as DNA methylation pattern, microRNA expression, and various histone modifications [5]. In the case of SLE, certain epigenetic changes are detected in SLE patients and can act as biomarkers such as the widespread DNA hypomethylation pattern in CD4 T cells [63, 64] and DNA hypomethylation of the promoters of certain genes that encode immune mediators and are associated with SLE pathogenesis such as CD40L [65], CD70 [66], perforin [67], IL-10, and IL-13 [68, 69]. With reduced DNA methylation which normally acts as a repressive signal, the affected genes become highly activated and consequently activate T and B immune cells [5].

Another potential epigenetic biomarker for SLE is the aberrant changes in histone proteins modification patterns that are normally quintessential for controlling gene expression [70, 71]. Specific changes in histone modifications have been observed in immune cells of SLE patients [5] such as the widespread hypomethylation of lysine 9 residues in H3 histone protein in CD4 T cells [72].

In addition to histone modifications, changes in miRNA expression profile are promising SLE biomarkers [5]. MiRNAs are short noncoding RNA sequences that regulate gene expression via targeting and inhibiting mRNA transcripts [73]. It was recently discovered that miRNAs play important roles in both innate and adaptive immune systems and are involved in the pathogenesis of several autoimmune diseases including SLE [74–77]. Several studies have aimed at profiling miRNA expression patterns in SLE and have identified several miRNAs that were underexpressed in CD4 T cells isolated from SLE patients such as miRNA-146a [78, 79] and miRNA-125a [80]. Reduced levels of these miRNAs were inversely correlated with SLE activity as they were associated with increased activation of type I interferon and inflammatory chemokines, respectively.
