Genetics and Epigenetics of Autoimmune Diseases

Elucidating the interrelationships between genetic and epigenetic factors represents an important challenge in our knowledge of autoimmune diseases (AID). Accordingly, the first clues support (1) the initiating role of environmental factors (e.g. infectious agents, drugs, diet and UV light exposure) on the epigenetic machinery, (2) the presence of specific cell-type epigenetic marks in AID (DNA methylation/demethylation, histone modifications and chromatin organisation), (3) the critical role of epigenetic processes in the control of transposons and key immune protein-coding gene expression, (4) the presence of AID-associated genetic risk variants that are predominantly present within cell-type-specific and epigenetically controlled long-range gene-regulatory sequences and, last but not the least, (5) the detection of AID-specific transcriptome hallmarks that are in part related to microRNA dysregulation. Altogether, advances in our understanding of the mechanisms involved in the development of AID offer novel ways for the diagnosis, prognosis and therapy of AID patients. Key Concepts Autoimmune diseases (AID) are complex diseases. Genetics, epigenetics and environmental factors control AID. AID genetic risk variants are mainly located in the epigenetic AID-related hotspots. Epigenetic modifications are cell specific in AID. Environmental factors control cell-specific epigenetic modifications in AID. Keywords: genetics; epigenetics; DNA methylation; DNA demethylation; histone modifications; microRNAs; autoimmune diseases