The process of apoptosis or programmed cell death of activated lymphocytes is critical for immune homeostasis. The cell surface expression of the protein Fas and its ligand are pivotal in regulating lymphocyte apoptosis. In mice defective Fas expression results in a severe overaccumulation of mature lymphocytes and autoimmune disease.Mutations of the Fas gene have been described in humans. Clinically, this defect in Fas expression results in autoimmune lymphoproliferative syndrome (ALPS). Several kindreds with ALPS have been identified and followed for several years. Clinically, massive splenomegaly and lymphadenopathy, hypergammaglobulinemia, autoimmunity, B cell lymphocytosis, and expansion of an unusual population of CD4 through CD8 T cells characterize ALPS. Commonly, the autoimmune phenomena include warm autoimmune hemolytic anemia, neutropenia, and thrombocytopenia.Characterization of features of autoimmunity in these patients and their family pedigrees is under way. They are being tested for antibodies to red cells, platelets, neutrophils, and HLA antigens. Studies of 25 patients have found that 16 had positive direct antiglobulin tests (DAT), six had platelet specific antibodies, and five had neutrophil specific antibodies. Family members with the Fas mutation who did not have ALPS did not have positive DATs. Among the patients with ALPS, females and younger patients were more likely to have red cell autoantibodies.
