Autoinflammatory diseases were first recognized nearly 20 years ago as distinct clinical and immunological entities caused by dysregulation in the innate immune system. Currently, autoinflammatory diseases comprise a wide range of disorders with the common features of recurrent fever attacks, prevalence of hyperreactive innate immune cells, and signs of inflammation that can be systemic or organ specific in the absence of pathogenic infection of autoimmunity. Advanced genomic techniques have led to the identification of new monogenic disorders and their corresponding signaling pathways. Innate immune cells from the myeloid compartment are the main effectors of uncontrolled inflammation that is caused in great extent by the overproduction of inflammatory cytokines such as IL-1β and IL-18.
In a recent review article by Alvarez-Errico et al.* data that are currently available to describe the contribution of epigenetic mechanisms in autoinflammatory diseases are presented and discussed. The possibility that other causative mechanisms may lead to amplified autoimmune inflammation in both mutated and non-mutated pathogenic genes, increases the complexity of how auto-inflammatory diseases both manifest and develop. It is conceivable that different gene variants can behave differently depending on how they are associated with non-genetic backgrounds. This can in turn affect both disease presence and severity, from being a true cause mutation, a functional polymorphism or remain silent. The article also points out that in addition to more in-depth genetic studies using solid parallel sequencing techniques, epigenetic genomic profiling studies, it will also be of great value to investigate non-genetic landscapes that contribute to pathogenicity. Furthermore, the current genetic diagnosis of some candidate genes will expand potential biomarkers, taking into account clinical and molecular characteristics other than described mutations. The article concludes that the identification of epigenetic dysregulation that contributes to autoinflammation, allows them to address environmental contributions to autoinflammatory syndromes.
* Damiana Álvarez-Errico, et al. Genetic and Epigenetic Determinants in Autoinflammatory Diseases. Front Immunol. 2017, 8, 318.