Apoptosis and Autoimmunity: Lymphoproliferative Syndromes

Abstract

Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a genetically determined disease characterized by accumulation of lymphoid cells, hypergammaglobulinemia, and autoimmunity. It is caused by mutations in genes encoding components of the cell death pathway that is activated by the ligation of Fas, a member of the tumor necrosis factor (TNF) receptor family. Genotyping of family members of ALPS patients for Fas mutations usually reveals a dominant pattern of inheritance, but relatives that share the mutation often have no history of lymphadenopathy or autoimmune disease, even though their lymphocytes are resistant to apoptosis following ligation of Fas. Thi..