Immunological aspects of immunodeficiency diseases part 87

Studies of rare immunodeficiency syndromes, all of which are characterized by an increased tendency to develop HLH have identified a number of components required for the normal expression of cytolytic capacity by T cells and NK cells. The intracellular migration and docking of lytic granules requires the function of the small Rab GTPase, RAB27, which is mutated in the Griscelli syndrome characterized by partial albinism, immunodeficiency, and susceptibility to developing HLH. Defective cytolytic granule exocytosis is also  characteristic of patients with mutations of the gene encoding the protein MUNK13-4(UNC13D). The tSNARE syntexin 11, which is present in the trans-Golgi network, is also involved in intracellular vesicle trafficking. Mutation of these two genes is responsible for a further form of familial HLH.