What are the genetic changes related to autosomal recessive hyper-IgE syndrome ?
AR-HIES is usually caused by mutations in the DOCK8 gene. The protein produced from this gene plays a critical role in the survival and function of several types of immune system cells. One of the protein's functions is to help maintain the structure and integrity of immune cells called T cells and NK cells, which recognize and attack foreign invaders, particularly as these cells travel to sites of infection within the body. In addition, DOCK8 is involved in chemical signaling pathways that stimulate other immune cells called B cells to mature and produce antibodies, which are specialized proteins that attach to foreign particles and germs, marking them for destruction.  DOCK8 gene mutations result in the production of little or no functional DOCK8 protein. Shortage of this protein impairs normal immune cell development and function. It is thought that T cells and NK cells lacking DOCK8 cannot maintain their shape as they move through dense spaces, such as those found within the skin. The abnormal cells die, resulting in reduced numbers of these cells. A shortage of these immune cells impairs the immune response to foreign invaders, accounting for the severe viral skin infections common in AR-HIES. A lack of DOCK8 also impairs B cell maturation and the production of antibodies. A lack of this type of immune response leads to recurrent respiratory tract infections in people with this disorder. It is unclear how DOCK8 gene mutations are involved in other features of AR-HIES, such as the elevation of IgE levels, autoimmunity, and neurological problems.  Some people with AR-HIES do not have mutations in the DOCK8 gene. The genetic cause of the condition in these individuals is unknown.