Autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome, often shortened to ALPS, is a rare genetic form of lymphoproliferative disorder in which lymphocytes survive abnormally because Fas mediated apoptosis is defective. Normally the immune system down-regulates after an infection as Fas and Fas ligand trigger the death of activated B and T cells; in ALPS this pathway fails, leading to chronic non-malignant lymphoproliferation, autoimmune disease and an increased risk of cancers such as Hodgkin and non-Hodgkin lymphoma. Typical signs are enlarged lymph nodes and spleen, and the most common autoimmune problems are hemolytic anemia, neutropenia and thrombocytopenia. The condition is usually caused by mutations in the FAS gene and is inherited in an autosomal dominant manner with incomplete penetrance, so that up to 40 percent of people with a FAS mutation show no symptoms. Diagnosis rests on chronic non-malignant lymphoproliferation, elevated double-negative T cells and supporting laboratory criteria.