Epigenetics and human disease: translating basic biology into clinical applications David Rodenhiser and Mellissa Mann

“Immunity and related disorders

The activation of the immune response involves stepwise epigenetic changes, which allow individual cells to mount a specific immune response that can be maintained over multiple cell generations.90,91 For example, shifts in both acetylation and methylation are required to coordinate DNA accessibility and permit recombination, thereby allowing cells to mount an immune response against a specific antigen.92 Recent reports suggest that loss of epigenetic control over this complex process contributes to autoimmune disease. Abnormal DNA methylation has been observed in patients with lupus whose T cells exhibit decreased extracellular signal-regulated kinase pathway signalling, decreased methyltransferase activity and hypomethylated DNA.93 Disregulation of this pathway apparently leads to overexpression of methylation-sensitive genes such as the leukocyte function-associated factor (LFA1), which causes lupus-like autoimmunity.93,94 Interestingly, LFA1 expression is also required for the development of arthritis, which raises the possibility that altered DNA methylation patterns may contribute to other diseases displaying idiopathic autoimmunity.95”

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