Updated overview of molecular pathways involved in the most common monogenic autoinflammatory diseases.

An apparently unprovoked recurrent inflammation is the quintessential hallmark of autoinflammatory diseases (AIDs), a large and heterogeneous group of disorders in which there is poor regulation of the innate immune system with no clearly demonstrated autoimmune machinery involvement. Innate immunity pathways are diverse and our understanding of their molecular composition and function is continuously expanding. The impaired immune responses we observe in monogenic AIDs, mostly in the hereditary periodic fever syndromes, is officiated by target molecules of microbial origin (pathogen-associated molecular patterns) and also host molecules (danger-associated molecular patterns). Further crucial components of innate immune mechanisms that contribute differently in the deregulated inflammatory patterns of different AIDs include Toll-like receptors, Nod-like receptors, scaffolding proteins (such as the caspase recruitment domain of proteins), cytosolic DNA-sensing molecules, inflammatory multi-protein complexes (referred to as inflammasomes), complement system, and others. In recent years, the knowledge of protean molecular pathways responsible for the most common monogenic AIDs has expanded, in parallel with very recent extraordinary technological advances, allowing the identification and characterisation of some unknown aspects of the innate immunity. This review will list and describe the most common monogenic febrile syndromes belonging to AIDs and will focus on current insights dealing with their pathologic processes.