Moyamoya disease emerging as an immune-related angiopathy.

Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. MMD is characterized by progressive narrowing of arteries of the brain and the formation of a compensatory network of fragile vessels. Genetic studies have identified RNF213, also known as mysterin, as a susceptibility gene for MMD, but the low penetrance in genetically susceptible individuals suggests that a second hit is necessary to trigger disease onset. Recently, several molecular studies uncovered RNF213 as a key antimicrobial protein with important functions in the immune system. In addition, an increasing number of clinical reports describe the development of moyamoya angiopathy (MMA) associated with infection or autoimmune disorders. Together, this growing body of molecular and clinical evidence points towards immune-related responses as second hits to trigger MMD onset.