Apoptosis (programmed cell death) of activated lymphocytes is critical for immune homeostasis. The cell surface protein (Fas) and its ligand are pivotal in regulating lymphocyte apoptosis. Defective Fas expression results in a severe overaccumulation of mature lymphs and autoimmune disease in mice. Mutations of the Fas gene in humans results in autoimmune lymphoproliferative syndrome (ALPS). Several ALPS kindreds have been identified and followed for several years. Clinically, ALPS is characterized by massive splenomegaly and lymphadenopathy, hypergammaglobulinemia, autoimmunity, B cell lymphocytosis, and expansion of an unusual population of CD4 through CD8 T cells. Commonly, the autoimmune phenomena include warm autoimmune hemolytic anemia, neutropenia, and thrombocytopenia. Characterization of features of autoimmunity and alloimmunity in these patients and their family pedigrees is under way as these features relate to red blood cell serology, frequency, and specificity of antiplatelet and antineutrophil antibodies and human leukocyte antigen class I and Il typing of cases with pedigreed family members.
