Hyper immunoglobulin E syndrome is a rare inherited disease, associated with abnormalities of the skin, sinuses, lungs, bones, and teeth. It is caused by mutations in a gene on the X chromosome that encodes specific protein of T and Natural killer cells (NK cells) called SAP.
In the absence of SAP, lymphocytes proliferate unchecked in response to Epstein- Barr virus (EBV) infection, and NK cells do not function. Abnormal response of T-cells and natural killer cell to Epstein-Barr virus infection, leads to liver failure, immunodeficiency, lymphoma, fatal lymph proliferative disease, or bone marrow aphasia.
The syndrome is usually asymptomatic until EBV infection develops. About 75% of patients die by age 10, and all die by age 40 unless bone marrow transplantation is done.
SAP is a 15kDa protein associated with SLAM protein. SLAM (Signaling Lymphocyte-Activation Molecule) is a glycosylated type-I transmembrane protein which is present on the surface of B and T cells. SLAM is a high-affinity self-ligand which, when triggered, co-activated B or T lymphocyte responses and is considered to be important in bi-directional T – B cell stimulation.