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 over accumulation 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. They are also being typed for HLA class I and II antigens. The results of the antibody tests and HLA typings are being correlated with clinical features. Studies of Il patients have found that 9 had positive direct antiglobulin tests (DAT), 7 had platelet specific antibodies and 3 had neutrophil specific antibodies. Newly diagnosed patients will be tested to determine if the presence of antibodies correlates with anemia, thrombocytopenia or neutropenia. Attempts will be made to identify the antigenic targets of the autoantibodies.
